[{"month":"06","publication_identifier":{"eissn":["1664-302X"]},"isi":1,"quality_controlled":"1","external_id":{"pmid":["37485524"],"isi":["001030002600001"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"language":[{"iso":"eng"}],"doi":"10.3389/fmicb.2023.1049255","article_number":"1049255","license":"https://creativecommons.org/licenses/by/4.0/","file_date_updated":"2023-07-31T07:16:34Z","publication_status":"published","publisher":"Frontiers","department":[{"_id":"CaGu"}],"year":"2023","acknowledgement":"This work was supported by NIH P50 award P50GM081892-02 to the University of Chicago, a catalyst grant from the Chicago Biomedical Consortium with support from The Searle Funds at The Chicago Community Trust to PC, and a Yen Fellowship to CCG. MA was partially supported by PAPIIT-UNAM grant IN-11322.","pmid":1,"date_created":"2023-02-02T08:13:28Z","date_updated":"2023-08-02T06:25:04Z","volume":14,"author":[{"full_name":"Guet, Calin C","last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Bruneaux, L","last_name":"Bruneaux","first_name":"L"},{"full_name":"Oikonomou, P","last_name":"Oikonomou","first_name":"P"},{"full_name":"Aldana, M","first_name":"M","last_name":"Aldana"},{"last_name":"Cluzel","first_name":"P","full_name":"Cluzel, P"}],"scopus_import":"1","day":"20","article_processing_charge":"Yes","has_accepted_license":"1","article_type":"original","publication":"Frontiers in Microbiology","citation":{"chicago":"Guet, Calin C, L Bruneaux, P Oikonomou, M Aldana, and P Cluzel. “Monitoring Lineages of Growing and Dividing Bacteria Reveals an Inducible Memory of Mar Operon Expression.” Frontiers in Microbiology. Frontiers, 2023. https://doi.org/10.3389/fmicb.2023.1049255.","short":"C.C. Guet, L. Bruneaux, P. Oikonomou, M. Aldana, P. Cluzel, Frontiers in Microbiology 14 (2023).","mla":"Guet, Calin C., et al. “Monitoring Lineages of Growing and Dividing Bacteria Reveals an Inducible Memory of Mar Operon Expression.” Frontiers in Microbiology, vol. 14, 1049255, Frontiers, 2023, doi:10.3389/fmicb.2023.1049255.","apa":"Guet, C. C., Bruneaux, L., Oikonomou, P., Aldana, M., & Cluzel, P. (2023). Monitoring lineages of growing and dividing bacteria reveals an inducible memory of mar operon expression. Frontiers in Microbiology. Frontiers. https://doi.org/10.3389/fmicb.2023.1049255","ieee":"C. C. Guet, L. Bruneaux, P. Oikonomou, M. Aldana, and P. Cluzel, “Monitoring lineages of growing and dividing bacteria reveals an inducible memory of mar operon expression,” Frontiers in Microbiology, vol. 14. Frontiers, 2023.","ista":"Guet CC, Bruneaux L, Oikonomou P, Aldana M, Cluzel P. 2023. Monitoring lineages of growing and dividing bacteria reveals an inducible memory of mar operon expression. Frontiers in Microbiology. 14, 1049255.","ama":"Guet CC, Bruneaux L, Oikonomou P, Aldana M, Cluzel P. Monitoring lineages of growing and dividing bacteria reveals an inducible memory of mar operon expression. Frontiers in Microbiology. 2023;14. doi:10.3389/fmicb.2023.1049255"},"date_published":"2023-06-20T00:00:00Z","type":"journal_article","abstract":[{"text":"In Gram negative bacteria, the multiple antibiotic resistance or mar operon, is known to control the expression of multi-drug efflux genes that protect bacteria from a wide range of drugs. As many different chemical compounds can induce this operon, identifying the parameters that govern the dynamics of its induction is crucial to better characterize the processes of tolerance and resistance. Most experiments have assumed that the properties of the mar transcriptional network can be inferred from population measurements. However, measurements from an asynchronous population of cells can mask underlying phenotypic variations of single cells. We monitored the activity of the mar promoter in single Escherichia coli cells in linear micro-colonies and established that the response to a steady level of inducer was most heterogeneous within individual colonies for an intermediate value of inducer. Specifically, sub-lineages defined by contiguous daughter-cells exhibited similar promoter activity, whereas activity was greatly variable between different sub-lineages. Specific sub-trees of uniform promoter activity persisted over several generations. Statistical analyses of the lineages suggest that the presence of these sub-trees is the signature of an inducible memory of the promoter state that is transmitted from mother to daughter cells. This single-cell study reveals that the degree of epigenetic inheritance changes as a function of inducer concentration, suggesting that phenotypic inheritance may be an inducible phenotype.","lang":"eng"}],"status":"public","ddc":["570"],"title":"Monitoring lineages of growing and dividing bacteria reveals an inducible memory of mar operon expression","intvolume":" 14","_id":"12478","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Published Version","file":[{"file_size":6452841,"content_type":"application/pdf","creator":"dernst","access_level":"open_access","file_name":"2023_FrontiersMicrobiology_Guet.pdf","checksum":"7dd322347512afaa5daf72a0154f2f07","success":1,"date_updated":"2023-07-31T07:16:34Z","date_created":"2023-07-31T07:16:34Z","relation":"main_file","file_id":"13322"}]},{"article_type":"original","publication":"PLoS Computational Biology","citation":{"ista":"Davidović A, Chait RP, Batt G, Ruess J. 2022. Parameter inference for stochastic biochemical models from perturbation experiments parallelised at the single cell level. PLoS Computational Biology. 18(3), e1009950.","ieee":"A. Davidović, R. P. Chait, G. Batt, and J. Ruess, “Parameter inference for stochastic biochemical models from perturbation experiments parallelised at the single cell level,” PLoS Computational Biology, vol. 18, no. 3. Public Library of Science, 2022.","apa":"Davidović, A., Chait, R. P., Batt, G., & Ruess, J. (2022). Parameter inference for stochastic biochemical models from perturbation experiments parallelised at the single cell level. PLoS Computational Biology. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1009950","ama":"Davidović A, Chait RP, Batt G, Ruess J. Parameter inference for stochastic biochemical models from perturbation experiments parallelised at the single cell level. PLoS Computational Biology. 2022;18(3). doi:10.1371/journal.pcbi.1009950","chicago":"Davidović, Anđela, Remy P Chait, Gregory Batt, and Jakob Ruess. “Parameter Inference for Stochastic Biochemical Models from Perturbation Experiments Parallelised at the Single Cell Level.” PLoS Computational Biology. Public Library of Science, 2022. https://doi.org/10.1371/journal.pcbi.1009950.","mla":"Davidović, Anđela, et al. “Parameter Inference for Stochastic Biochemical Models from Perturbation Experiments Parallelised at the Single Cell Level.” PLoS Computational Biology, vol. 18, no. 3, e1009950, Public Library of Science, 2022, doi:10.1371/journal.pcbi.1009950.","short":"A. Davidović, R.P. Chait, G. Batt, J. Ruess, PLoS Computational Biology 18 (2022)."},"date_published":"2022-03-18T00:00:00Z","scopus_import":"1","day":"18","has_accepted_license":"1","article_processing_charge":"No","ddc":["570","000"],"status":"public","title":"Parameter inference for stochastic biochemical models from perturbation experiments parallelised at the single cell level","intvolume":" 18","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"10939","file":[{"access_level":"open_access","file_name":"2022_PLoSCompBio_Davidovic.pdf","content_type":"application/pdf","file_size":2958642,"creator":"dernst","relation":"main_file","file_id":"10947","checksum":"458ef542761fb714ced214f240daf6b2","success":1,"date_created":"2022-04-04T10:14:39Z","date_updated":"2022-04-04T10:14:39Z"}],"oa_version":"Published Version","type":"journal_article","abstract":[{"text":"Understanding and characterising biochemical processes inside single cells requires experimental platforms that allow one to perturb and observe the dynamics of such processes as well as computational methods to build and parameterise models from the collected data. Recent progress with experimental platforms and optogenetics has made it possible to expose each cell in an experiment to an individualised input and automatically record cellular responses over days with fine time resolution. However, methods to infer parameters of stochastic kinetic models from single-cell longitudinal data have generally been developed under the assumption that experimental data is sparse and that responses of cells to at most a few different input perturbations can be observed. Here, we investigate and compare different approaches for calculating parameter likelihoods of single-cell longitudinal data based on approximations of the chemical master equation (CME) with a particular focus on coupling the linear noise approximation (LNA) or moment closure methods to a Kalman filter. We show that, as long as cells are measured sufficiently frequently, coupling the LNA to a Kalman filter allows one to accurately approximate likelihoods and to infer model parameters from data even in cases where the LNA provides poor approximations of the CME. Furthermore, the computational cost of filtering-based iterative likelihood evaluation scales advantageously in the number of measurement times and different input perturbations and is thus ideally suited for data obtained from modern experimental platforms. To demonstrate the practical usefulness of these results, we perform an experiment in which single cells, equipped with an optogenetic gene expression system, are exposed to various different light-input sequences and measured at several hundred time points and use parameter inference based on iterative likelihood evaluation to parameterise a stochastic model of the system.","lang":"eng"}],"issue":"3","quality_controlled":"1","oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"language":[{"iso":"eng"}],"doi":"10.1371/journal.pcbi.1009950","month":"03","publication_identifier":{"eissn":["1553-7358"],"issn":["1553-734X"]},"publication_status":"published","department":[{"_id":"CaGu"}],"publisher":"Public Library of Science","acknowledgement":"We thank Virgile Andreani for useful discussions about the model and parameter inference. We thank Johan Paulsson and Jeffrey J Tabor for kind gifts of plasmids. R was supported by the ANR grant CyberCircuits (ANR-18-CE91-0002). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","year":"2022","date_updated":"2022-04-04T10:21:53Z","date_created":"2022-04-03T22:01:42Z","volume":18,"author":[{"full_name":"Davidović, Anđela","first_name":"Anđela","last_name":"Davidović"},{"id":"3464AE84-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0876-3187","first_name":"Remy P","last_name":"Chait","full_name":"Chait, Remy P"},{"first_name":"Gregory","last_name":"Batt","full_name":"Batt, Gregory"},{"first_name":"Jakob","last_name":"Ruess","id":"4A245D00-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1615-3282","full_name":"Ruess, Jakob"}],"related_material":{"link":[{"url":"https://gitlab.pasteur.fr/adavidov/inferencelnakf","relation":"software"}]},"article_number":"e1009950","file_date_updated":"2022-04-04T10:14:39Z"},{"_id":"11713","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","ddc":["570"],"title":"Quantifying heterologous gene expression during ectopic MazF production in Escherichia coli","intvolume":" 15","oa_version":"Published Version","file":[{"creator":"dernst","content_type":"application/pdf","file_size":1545310,"access_level":"open_access","file_name":"2022_BMCResearchNotes_Nikolic.pdf","success":1,"checksum":"008156e5340e9789f0f6d82bde4d347a","date_created":"2022-08-01T09:24:42Z","date_updated":"2022-08-01T09:24:42Z","file_id":"11714","relation":"main_file"}],"type":"journal_article","abstract":[{"lang":"eng","text":"Objective: MazF is a sequence-specific endoribonuclease-toxin of the MazEF toxin–antitoxin system. MazF cleaves single-stranded ribonucleic acid (RNA) regions at adenine–cytosine–adenine (ACA) sequences in the bacterium Escherichia coli. The MazEF system has been used in various biotechnology and synthetic biology applications. In this study, we infer how ectopic mazF overexpression affects production of heterologous proteins. To this end, we quantified the levels of fluorescent proteins expressed in E. coli from reporters translated from the ACA-containing or ACA-less messenger RNAs (mRNAs). Additionally, we addressed the impact of the 5′-untranslated region of these reporter mRNAs under the same conditions by comparing expression from mRNAs that comprise (canonical mRNA) or lack this region (leaderless mRNA).\r\nResults: Flow cytometry analysis indicates that during mazF overexpression, fluorescent proteins are translated from the canonical as well as leaderless mRNAs. Our analysis further indicates that longer mazF overexpression generally increases the concentration of fluorescent proteins translated from ACA-less mRNAs, however it also substantially increases bacterial population heterogeneity. Finally, our results suggest that the strength and duration of mazF overexpression should be optimized for each experimental setup, to maximize the heterologous protein production and minimize the amount of phenotypic heterogeneity in bacterial populations, which is unfavorable in biotechnological processes."}],"publication":"BMC Research Notes","citation":{"mla":"Nikolic, Nela, et al. “Quantifying Heterologous Gene Expression during Ectopic MazF Production in Escherichia Coli.” BMC Research Notes, vol. 15, 173, Springer Nature, 2022, doi:10.1186/s13104-022-06061-9.","short":"N. Nikolic, M. Sauert, T.G. Albanese, I. Moll, BMC Research Notes 15 (2022).","chicago":"Nikolic, Nela, Martina Sauert, Tanino G. Albanese, and Isabella Moll. “Quantifying Heterologous Gene Expression during Ectopic MazF Production in Escherichia Coli.” BMC Research Notes. Springer Nature, 2022. https://doi.org/10.1186/s13104-022-06061-9.","ama":"Nikolic N, Sauert M, Albanese TG, Moll I. Quantifying heterologous gene expression during ectopic MazF production in Escherichia coli. BMC Research Notes. 2022;15. doi:10.1186/s13104-022-06061-9","ista":"Nikolic N, Sauert M, Albanese TG, Moll I. 2022. Quantifying heterologous gene expression during ectopic MazF production in Escherichia coli. BMC Research Notes. 15, 173.","ieee":"N. Nikolic, M. Sauert, T. G. Albanese, and I. Moll, “Quantifying heterologous gene expression during ectopic MazF production in Escherichia coli,” BMC Research Notes, vol. 15. Springer Nature, 2022.","apa":"Nikolic, N., Sauert, M., Albanese, T. G., & Moll, I. (2022). Quantifying heterologous gene expression during ectopic MazF production in Escherichia coli. BMC Research Notes. Springer Nature. https://doi.org/10.1186/s13104-022-06061-9"},"article_type":"letter_note","date_published":"2022-05-13T00:00:00Z","scopus_import":"1","keyword":["General Biochemistry","Genetics and Molecular Biology","General Medicine"],"day":"13","has_accepted_license":"1","article_processing_charge":"No","year":"2022","acknowledgement":"We acknowledge the Max Perutz Labs FACS Facility together with Thomas Sauer. NN is grateful to Călin C. Guet for his support.\r\nThis work was funded by the Elise Richter grant V738 of the Austrian Science Fund (FWF), and the FWF Lise Meitner grant M1697, to NN; and by the FWF grant P22249, FWF Special Research Program RNA-REG F43 (subproject F4316), and FWF doctoral program RNA Biology (W1207), to IM. Open access funding provided by the Austrian Science Fund.","pmid":1,"publication_status":"published","publisher":"Springer Nature","department":[{"_id":"CaGu"}],"author":[{"full_name":"Nikolic, Nela","id":"42D9CABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9068-6090","first_name":"Nela","last_name":"Nikolic"},{"full_name":"Sauert, Martina","first_name":"Martina","last_name":"Sauert"},{"first_name":"Tanino G.","last_name":"Albanese","full_name":"Albanese, Tanino G."},{"full_name":"Moll, Isabella","last_name":"Moll","first_name":"Isabella"}],"related_material":{"link":[{"url":"https://doi.org/10.1186/s13104-022-06152-7","relation":"erratum"}]},"date_created":"2022-08-01T09:04:27Z","date_updated":"2022-08-01T09:27:40Z","volume":15,"article_number":"173","file_date_updated":"2022-08-01T09:24:42Z","oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"pmid":["35562780"]},"quality_controlled":"1","project":[{"_id":"26956E74-B435-11E9-9278-68D0E5697425","grant_number":"V00738","call_identifier":"FWF","name":"Bacterial toxin-antitoxin systems as antiphage defense mechanisms"}],"doi":"10.1186/s13104-022-06061-9","language":[{"iso":"eng"}],"month":"05","publication_identifier":{"issn":["1756-0500"]}},{"ec_funded":1,"file_date_updated":"2022-02-07T07:14:09Z","article_number":"e64543","volume":11,"date_created":"2022-02-06T23:01:32Z","date_updated":"2023-08-02T14:09:02Z","author":[{"id":"345D25EC-F248-11E8-B48F-1D18A9856A87","first_name":"Mato","last_name":"Lagator","full_name":"Lagator, Mato"},{"first_name":"Srdjan","last_name":"Sarikas","id":"35F0286E-F248-11E8-B48F-1D18A9856A87","full_name":"Sarikas, Srdjan"},{"last_name":"Steinrueck","first_name":"Magdalena","full_name":"Steinrueck, Magdalena"},{"last_name":"Toledo-Aparicio","first_name":"David","full_name":"Toledo-Aparicio, David"},{"orcid":"0000-0002-4624-4612","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","last_name":"Bollback","first_name":"Jonathan P","full_name":"Bollback, Jonathan P"},{"full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C"},{"full_name":"Tkačik, Gašper","last_name":"Tkačik","first_name":"Gašper","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"}],"publisher":"eLife Sciences Publications","department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"NiBa"}],"publication_status":"published","pmid":1,"year":"2022","acknowledgement":"We thank Hande Acar, Nicholas H Barton, Rok Grah, Tiago Paixao, Maros Pleska, Anna Staron, and Murat Tugrul for insightful comments and input on the manuscript. This work was supported by: Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant number 216779/Z/19/Z) to ML; IPC Grant from IST Austria to ML and SS; European Research Council Funding Programme 7 (2007–2013, grant agreement number 648440) to JPB.","publication_identifier":{"eissn":["2050-084X"]},"month":"01","language":[{"iso":"eng"}],"doi":"10.7554/eLife.64543","project":[{"_id":"2578D616-B435-11E9-9278-68D0E5697425","grant_number":"648440","name":"Selective Barriers to Horizontal Gene Transfer","call_identifier":"H2020"}],"quality_controlled":"1","isi":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"pmid":["35080492"],"isi":["000751104400001"]},"oa":1,"abstract":[{"text":"Predicting function from sequence is a central problem of biology. Currently, this is possible only locally in a narrow mutational neighborhood around a wildtype sequence rather than globally from any sequence. Using random mutant libraries, we developed a biophysical model that accounts for multiple features of σ70 binding bacterial promoters to predict constitutive gene expression levels from any sequence. We experimentally and theoretically estimated that 10–20% of random sequences lead to expression and ~80% of non-expressing sequences are one mutation away from a functional promoter. The potential for generating expression from random sequences is so pervasive that selection acts against σ70-RNA polymerase binding sites even within inter-genic, promoter-containing regions. This pervasiveness of σ70-binding sites implies that emergence of promoters is not the limiting step in gene regulatory evolution. Ultimately, the inclusion of novel features of promoter function into a mechanistic model enabled not only more accurate predictions of gene expression levels, but also identified that promoters evolve more rapidly than previously thought.","lang":"eng"}],"type":"journal_article","oa_version":"Published Version","file":[{"access_level":"open_access","file_name":"2022_ELife_Lagator.pdf","creator":"cchlebak","file_size":5604343,"content_type":"application/pdf","file_id":"10739","relation":"main_file","success":1,"checksum":"decdcdf600ff51e9a9703b49ca114170","date_created":"2022-02-07T07:14:09Z","date_updated":"2022-02-07T07:14:09Z"}],"intvolume":" 11","ddc":["576"],"title":"Predicting bacterial promoter function and evolution from random sequences","status":"public","_id":"10736","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"No","has_accepted_license":"1","day":"26","scopus_import":"1","date_published":"2022-01-26T00:00:00Z","article_type":"original","citation":{"short":"M. Lagator, S. Sarikas, M. Steinrueck, D. Toledo-Aparicio, J.P. Bollback, C.C. Guet, G. Tkačik, ELife 11 (2022).","mla":"Lagator, Mato, et al. “Predicting Bacterial Promoter Function and Evolution from Random Sequences.” ELife, vol. 11, e64543, eLife Sciences Publications, 2022, doi:10.7554/eLife.64543.","chicago":"Lagator, Mato, Srdjan Sarikas, Magdalena Steinrueck, David Toledo-Aparicio, Jonathan P Bollback, Calin C Guet, and Gašper Tkačik. “Predicting Bacterial Promoter Function and Evolution from Random Sequences.” ELife. eLife Sciences Publications, 2022. https://doi.org/10.7554/eLife.64543.","ama":"Lagator M, Sarikas S, Steinrueck M, et al. Predicting bacterial promoter function and evolution from random sequences. eLife. 2022;11. doi:10.7554/eLife.64543","apa":"Lagator, M., Sarikas, S., Steinrueck, M., Toledo-Aparicio, D., Bollback, J. P., Guet, C. C., & Tkačik, G. (2022). Predicting bacterial promoter function and evolution from random sequences. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.64543","ieee":"M. Lagator et al., “Predicting bacterial promoter function and evolution from random sequences,” eLife, vol. 11. eLife Sciences Publications, 2022.","ista":"Lagator M, Sarikas S, Steinrueck M, Toledo-Aparicio D, Bollback JP, Guet CC, Tkačik G. 2022. Predicting bacterial promoter function and evolution from random sequences. eLife. 11, e64543."},"publication":"eLife"},{"keyword":["General Immunology and Microbiology","Microbiology","Infectious Diseases"],"scopus_import":"1","article_processing_charge":"No","day":"01","page":"478-490","article_type":"review","citation":{"chicago":"Römhild, Roderich, Mark Tobias Bollenbach, and Dan I. Andersson. “The Physiology and Genetics of Bacterial Responses to Antibiotic Combinations.” Nature Reviews Microbiology. Springer Nature, 2022. https://doi.org/10.1038/s41579-022-00700-5.","short":"R. Römhild, M.T. Bollenbach, D.I. Andersson, Nature Reviews Microbiology 20 (2022) 478–490.","mla":"Römhild, Roderich, et al. “The Physiology and Genetics of Bacterial Responses to Antibiotic Combinations.” Nature Reviews Microbiology, vol. 20, Springer Nature, 2022, pp. 478–90, doi:10.1038/s41579-022-00700-5.","ieee":"R. Römhild, M. T. Bollenbach, and D. I. Andersson, “The physiology and genetics of bacterial responses to antibiotic combinations,” Nature Reviews Microbiology, vol. 20. Springer Nature, pp. 478–490, 2022.","apa":"Römhild, R., Bollenbach, M. T., & Andersson, D. I. (2022). The physiology and genetics of bacterial responses to antibiotic combinations. Nature Reviews Microbiology. Springer Nature. https://doi.org/10.1038/s41579-022-00700-5","ista":"Römhild R, Bollenbach MT, Andersson DI. 2022. The physiology and genetics of bacterial responses to antibiotic combinations. Nature Reviews Microbiology. 20, 478–490.","ama":"Römhild R, Bollenbach MT, Andersson DI. The physiology and genetics of bacterial responses to antibiotic combinations. Nature Reviews Microbiology. 2022;20:478-490. doi:10.1038/s41579-022-00700-5"},"publication":"Nature Reviews Microbiology","date_published":"2022-08-01T00:00:00Z","type":"journal_article","abstract":[{"lang":"eng","text":"Several promising strategies based on combining or cycling different antibiotics have been proposed to increase efficacy and counteract resistance evolution, but we still lack a deep understanding of the physiological responses and genetic mechanisms that underlie antibiotic interactions and the clinical applicability of these strategies. In antibiotic-exposed bacteria, the combined effects of physiological stress responses and emerging resistance mutations (occurring at different time scales) generate complex and often unpredictable dynamics. In this Review, we present our current understanding of bacterial cell physiology and genetics of responses to antibiotics. We emphasize recently discovered mechanisms of synergistic and antagonistic drug interactions, hysteresis in temporal interactions between antibiotics that arise from microbial physiology and interactions between antibiotics and resistance mutations that can cause collateral sensitivity or cross-resistance. We discuss possible connections between the different phenomena and indicate relevant research directions. A better and more unified understanding of drug and genetic interactions is likely to advance antibiotic therapy."}],"intvolume":" 20","title":"The physiology and genetics of bacterial responses to antibiotic combinations","status":"public","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"10812","oa_version":"None","publication_identifier":{"issn":["1740-1526"],"eissn":["1740-1534"]},"month":"08","quality_controlled":"1","isi":1,"external_id":{"pmid":["35241807"],"isi":["000763891900001"]},"language":[{"iso":"eng"}],"doi":"10.1038/s41579-022-00700-5","publisher":"Springer Nature","department":[{"_id":"CaGu"}],"publication_status":"published","pmid":1,"year":"2022","acknowledgement":"The authors thank B. Kavčič and H. Schulenburg for constructive feedback on the manuscript.","volume":20,"date_created":"2022-03-04T04:33:49Z","date_updated":"2023-08-02T14:41:44Z","author":[{"full_name":"Römhild, Roderich","id":"68E56E44-62B0-11EA-B963-444F3DDC885E","orcid":"0000-0001-9480-5261","first_name":"Roderich","last_name":"Römhild"},{"full_name":"Bollenbach, Mark Tobias","last_name":"Bollenbach","first_name":"Mark Tobias","orcid":"0000-0003-4398-476X","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Dan I.","last_name":"Andersson","full_name":"Andersson, Dan I."}]},{"file":[{"date_updated":"2022-05-02T06:26:26Z","date_created":"2022-05-02T06:26:26Z","success":1,"checksum":"7c6f76ab17393d650825cc240edc84b3","file_id":"11342","relation":"main_file","creator":"dernst","content_type":"application/pdf","file_size":2827723,"file_name":"2022_CommBiology_Glover.pdf","access_level":"open_access"}],"oa_version":"Published Version","ddc":["570"],"title":"Nutrient and salt depletion synergistically boosts glucose metabolism in individual Escherichia coli cells","status":"public","intvolume":" 5","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"11339","abstract":[{"text":"The interaction between a cell and its environment shapes fundamental intracellular processes such as cellular metabolism. In most cases growth rate is treated as a proximal metric for understanding the cellular metabolic status. However, changes in growth rate might not reflect metabolic variations in individuals responding to environmental fluctuations. Here we use single-cell microfluidics-microscopy combined with transcriptomics, proteomics and mathematical modelling to quantify the accumulation of glucose within Escherichia coli cells. In contrast to the current consensus, we reveal that environmental conditions which are comparatively unfavourable for growth, where both nutrients and salinity are depleted, increase glucose accumulation rates in individual bacteria and population subsets. We find that these changes in metabolic function are underpinned by variations at the translational and posttranslational level but not at the transcriptional level and are not dictated by changes in cell size. The metabolic response-characteristics identified greatly advance our fundamental understanding of the interactions between bacteria and their environment and have important ramifications when investigating cellular processes where salinity plays an important role.","lang":"eng"}],"type":"journal_article","date_published":"2022-04-20T00:00:00Z","article_type":"original","publication":"Communications Biology","citation":{"ista":"Glover G, Voliotis M, Łapińska U, Invergo BM, Soanes D, O’Neill P, Moore K, Nikolic N, Petrov P, Milner DS, Roy S, Heesom K, Richards TA, Tsaneva-Atanasova K, Pagliara S. 2022. Nutrient and salt depletion synergistically boosts glucose metabolism in individual Escherichia coli cells. Communications Biology. 5, 385.","ieee":"G. Glover et al., “Nutrient and salt depletion synergistically boosts glucose metabolism in individual Escherichia coli cells,” Communications Biology, vol. 5. Springer Nature, 2022.","apa":"Glover, G., Voliotis, M., Łapińska, U., Invergo, B. M., Soanes, D., O’Neill, P., … Pagliara, S. (2022). Nutrient and salt depletion synergistically boosts glucose metabolism in individual Escherichia coli cells. Communications Biology. Springer Nature. https://doi.org/10.1038/s42003-022-03336-6","ama":"Glover G, Voliotis M, Łapińska U, et al. Nutrient and salt depletion synergistically boosts glucose metabolism in individual Escherichia coli cells. Communications Biology. 2022;5. doi:10.1038/s42003-022-03336-6","chicago":"Glover, Georgina, Margaritis Voliotis, Urszula Łapińska, Brandon M. Invergo, Darren Soanes, Paul O’Neill, Karen Moore, et al. “Nutrient and Salt Depletion Synergistically Boosts Glucose Metabolism in Individual Escherichia Coli Cells.” Communications Biology. Springer Nature, 2022. https://doi.org/10.1038/s42003-022-03336-6.","mla":"Glover, Georgina, et al. “Nutrient and Salt Depletion Synergistically Boosts Glucose Metabolism in Individual Escherichia Coli Cells.” Communications Biology, vol. 5, 385, Springer Nature, 2022, doi:10.1038/s42003-022-03336-6.","short":"G. Glover, M. Voliotis, U. Łapińska, B.M. Invergo, D. Soanes, P. O’Neill, K. Moore, N. Nikolic, P. Petrov, D.S. Milner, S. Roy, K. Heesom, T.A. Richards, K. Tsaneva-Atanasova, S. Pagliara, Communications Biology 5 (2022)."},"day":"20","article_processing_charge":"No","has_accepted_license":"1","scopus_import":"1","date_updated":"2023-08-03T06:45:26Z","date_created":"2022-05-01T22:01:41Z","volume":5,"author":[{"full_name":"Glover, Georgina","last_name":"Glover","first_name":"Georgina"},{"full_name":"Voliotis, Margaritis","last_name":"Voliotis","first_name":"Margaritis"},{"first_name":"Urszula","last_name":"Łapińska","full_name":"Łapińska, Urszula"},{"first_name":"Brandon M.","last_name":"Invergo","full_name":"Invergo, Brandon M."},{"first_name":"Darren","last_name":"Soanes","full_name":"Soanes, Darren"},{"full_name":"O’Neill, Paul","last_name":"O’Neill","first_name":"Paul"},{"full_name":"Moore, Karen","first_name":"Karen","last_name":"Moore"},{"full_name":"Nikolic, Nela","id":"42D9CABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9068-6090","first_name":"Nela","last_name":"Nikolic"},{"full_name":"Petrov, Peter","last_name":"Petrov","first_name":"Peter"},{"full_name":"Milner, David S.","last_name":"Milner","first_name":"David S."},{"full_name":"Roy, Sumita","last_name":"Roy","first_name":"Sumita"},{"full_name":"Heesom, Kate","first_name":"Kate","last_name":"Heesom"},{"full_name":"Richards, Thomas A.","last_name":"Richards","first_name":"Thomas A."},{"full_name":"Tsaneva-Atanasova, Krasimira","first_name":"Krasimira","last_name":"Tsaneva-Atanasova"},{"full_name":"Pagliara, Stefano","last_name":"Pagliara","first_name":"Stefano"}],"publication_status":"published","publisher":"Springer Nature","department":[{"_id":"CaGu"}],"year":"2022","acknowledgement":"G.G. was supported by an EPSRC DTP PhD studentship (EP/M506527/1). M.V. and K.T.A. gratefully acknowledge financial support from the EPSRC (EP/N014391/1). U.L. was supported through a BBSRC grant (BB/V008021/1) and an MRC Proximity to Discovery EXCITEME2 grant (MCPC17189). This work was further supported by a Royal Society Research Grant (RG180007) awarded to S.P. and a QUEX Initiator grant awarded to S.P. and K.T.A.. D.S.M., T.A.R. and S.P.’s work in this area is also supported by a Marie Skłodowska-Curie project SINGEK (H2020-MSCA-ITN-2015-675752) and the Gordon and Betty Moore Foundation Marine Microbiology Initiative (GBMF5514). B.M.I. acknowledges support from a Wellcome Trust Institutional Strategic Support Award to the University of Exeter (204909/Z/16/Z). This project utilised equipment funded by the Wellcome Trust Institutional Strategic Support Fund (WT097835MF), Wellcome Trust Multi User Equipment Award (WT101650MA) and BBSRC LOLA award (BB/K003240/1).","pmid":1,"file_date_updated":"2022-05-02T06:26:26Z","article_number":"385","language":[{"iso":"eng"}],"doi":"10.1038/s42003-022-03336-6","quality_controlled":"1","isi":1,"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000784143400001"],"pmid":["35444215"]},"month":"04","publication_identifier":{"eissn":["2399-3642"]}},{"article_number":"e78995","file_date_updated":"2022-08-16T08:57:37Z","ec_funded":1,"acknowledgement":"We thank Ulrich Dobrindt for providing UPEC strains CFT073, UTI89, and 536, Frank Assen, Vlad Gavra, Maximilian Götz, Bor Kavčič, Jonna Alanko, and Eva Kiermaier for help with experiments and Robert Hauschild, Julian Stopp, and Saren Tasciyan for help with data analysis. We thank the IST Austria Scientific Service Units, especially the Bioimaging facility, the Preclinical facility and the Electron microscopy facility for technical support, Jakob Wallner and all members of the Guet and Sixt lab for fruitful discussions and Daria Siekhaus for critically reading the manuscript. This work was supported by grants from the Austrian Research Promotion Agency (FEMtech 868984) to IG, the European Research Council (CoG 724373), and the Austrian Science Fund (FWF P29911) to MS.","year":"2022","publication_status":"published","publisher":"eLife Sciences Publications","department":[{"_id":"MiSi"},{"_id":"CaGu"}],"author":[{"full_name":"Tomasek, Kathrin","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","last_name":"Tomasek","first_name":"Kathrin"},{"full_name":"Leithner, Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","first_name":"Alexander F","last_name":"Leithner"},{"id":"727b3c7d-4939-11ec-89b3-b9b0750ab74d","first_name":"Ivana","last_name":"Glatzová","full_name":"Glatzová, Ivana"},{"full_name":"Lukesch, Michael S.","last_name":"Lukesch","first_name":"Michael S."},{"orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C","full_name":"Guet, Calin C"},{"orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K","full_name":"Sixt, Michael K"}],"related_material":{"record":[{"relation":"earlier_version","status":"public","id":"10316"}]},"date_updated":"2023-08-03T12:54:21Z","date_created":"2022-08-14T22:01:46Z","volume":11,"month":"07","publication_identifier":{"eissn":["2050-084X"]},"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000838410200001"]},"quality_controlled":"1","isi":1,"project":[{"call_identifier":"H2020","name":"Cellular navigation along spatial gradients","grant_number":"724373","_id":"25FE9508-B435-11E9-9278-68D0E5697425"},{"name":"Mechanical adaptation of lamellipodial actin","call_identifier":"FWF","grant_number":"P29911","_id":"26018E70-B435-11E9-9278-68D0E5697425"}],"doi":"10.7554/eLife.78995","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"language":[{"iso":"eng"}],"type":"journal_article","abstract":[{"text":"A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on mouse dendritic cells (DCs) as a binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of the pathogenic strain CFT073 to CD14 reduced DC migration by overactivation of integrins and blunted expression of co-stimulatory molecules by overactivating the NFAT (nuclear factor of activated T-cells) pathway, both rate-limiting factors of T cell activation. This response was binary at the single-cell level, but averaged in larger populations exposed to both piliated and non-piliated pathogens, presumably via the exchange of immunomodulatory cytokines. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease.","lang":"eng"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"11843","title":"Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14","status":"public","ddc":["570"],"intvolume":" 11","file":[{"creator":"cchlebak","content_type":"application/pdf","file_size":2057577,"access_level":"open_access","file_name":"2022_eLife_Tomasek.pdf","success":1,"checksum":"002a3c7c7ea5caa9af9cfbea308f6ea4","date_updated":"2022-08-16T08:57:37Z","date_created":"2022-08-16T08:57:37Z","file_id":"11861","relation":"main_file"}],"oa_version":"Published Version","scopus_import":"1","day":"26","article_processing_charge":"Yes","has_accepted_license":"1","publication":"eLife","citation":{"apa":"Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., & Sixt, M. K. (2022). Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.78995","ieee":"K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M. K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14,” eLife, vol. 11. eLife Sciences Publications, 2022.","ista":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. 2022. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. eLife. 11, e78995.","ama":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. eLife. 2022;11. doi:10.7554/eLife.78995","chicago":"Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch, Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” ELife. eLife Sciences Publications, 2022. https://doi.org/10.7554/eLife.78995.","short":"K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt, ELife 11 (2022).","mla":"Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” ELife, vol. 11, e78995, eLife Sciences Publications, 2022, doi:10.7554/eLife.78995."},"article_type":"original","date_published":"2022-07-26T00:00:00Z"},{"type":"journal_article","abstract":[{"lang":"eng","text":"Together, copy-number and point mutations form the basis for most evolutionary novelty, through the process of gene duplication and divergence. While a plethora of genomic data reveals the long-term fate of diverging coding sequences and their cis-regulatory elements, little is known about the early dynamics around the duplication event itself. In microorganisms, selection for increased gene expression often drives the expansion of gene copy-number mutations, which serves as a crude adaptation, prior to divergence through refining point mutations. Using a simple synthetic genetic reporter system that can distinguish between copy-number and point mutations, we study their early and transient adaptive dynamics in real time in Escherichia coli. We find two qualitatively different routes of adaptation, depending on the level of functional improvement needed. In conditions of high gene expression demand, the two mutation types occur as a combination. However, under low gene expression demand, copy-number and point mutations are mutually exclusive; here, owing to their higher frequency, adaptation is dominated by copy-number mutations, in a process we term amplification hindrance. Ultimately, due to high reversal rates and pleiotropic cost, copy-number mutations may not only serve as a crude and transient adaptation, but also constrain sequence divergence over evolutionary time scales."}],"_id":"12333","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","ddc":["570"],"title":"Adaptation dynamics between copynumber and point mutations","status":"public","intvolume":" 11","file":[{"file_name":"2022_eLife_Tomanek.pdf","access_level":"open_access","creator":"dernst","content_type":"application/pdf","file_size":8835954,"file_id":"12338","relation":"main_file","date_created":"2023-01-23T08:56:21Z","date_updated":"2023-01-23T08:56:21Z","success":1,"checksum":"9321fd5f06ff59d5e2d33daee84b3da1"}],"oa_version":"Published Version","scopus_import":"1","day":"22","has_accepted_license":"1","article_processing_charge":"No","publication":"eLife","citation":{"ama":"Tomanek I, Guet CC. Adaptation dynamics between copynumber and point mutations. eLife. 2022;11. doi:10.7554/ELIFE.82240","ista":"Tomanek I, Guet CC. 2022. Adaptation dynamics between copynumber and point mutations. eLife. 11, e82240.","apa":"Tomanek, I., & Guet, C. C. (2022). Adaptation dynamics between copynumber and point mutations. ELife. eLife Sciences Publications. https://doi.org/10.7554/ELIFE.82240","ieee":"I. Tomanek and C. C. Guet, “Adaptation dynamics between copynumber and point mutations,” eLife, vol. 11. eLife Sciences Publications, 2022.","mla":"Tomanek, Isabella, and Calin C. Guet. “Adaptation Dynamics between Copynumber and Point Mutations.” ELife, vol. 11, e82240, eLife Sciences Publications, 2022, doi:10.7554/ELIFE.82240.","short":"I. Tomanek, C.C. Guet, ELife 11 (2022).","chicago":"Tomanek, Isabella, and Calin C Guet. “Adaptation Dynamics between Copynumber and Point Mutations.” ELife. eLife Sciences Publications, 2022. https://doi.org/10.7554/ELIFE.82240."},"article_type":"original","date_published":"2022-12-22T00:00:00Z","article_number":"e82240","file_date_updated":"2023-01-23T08:56:21Z","year":"2022","acknowledgement":"We are grateful to N Barton, F Kondrashov, M Lagator, M Pleska, R Roemhild, D Siekhaus, and G\r\nTkacik for input on the manuscript and to K Tomasek for help with flow cytometry.","publication_status":"published","publisher":"eLife Sciences Publications","department":[{"_id":"CaGu"}],"author":[{"full_name":"Tomanek, Isabella","id":"3981F020-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6197-363X","first_name":"Isabella","last_name":"Tomanek"},{"last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C"}],"related_material":{"link":[{"relation":"software","url":"https://doi.org/10.5281/zenodo.6974122"}],"record":[{"status":"public","relation":"research_data","id":"12339"}]},"date_created":"2023-01-22T23:00:55Z","date_updated":"2023-08-03T14:23:07Z","volume":11,"month":"12","publication_identifier":{"eissn":["2050-084X"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"external_id":{"isi":["000912674700001"]},"quality_controlled":"1","isi":1,"doi":"10.7554/ELIFE.82240","language":[{"iso":"eng"}]},{"article_processing_charge":"No","day":"23","month":"12","oa":1,"citation":{"chicago":"Tomanek, Isabella, and Calin C Guet. “Flow Cytometry YFP and CFP Data and Deep Sequencing Data of Populations Evolving in Galactose.” Dryad, 2022. https://doi.org/10.5061/dryad.rfj6q57ds.","mla":"Tomanek, Isabella, and Calin C. Guet. Flow Cytometry YFP and CFP Data and Deep Sequencing Data of Populations Evolving in Galactose. Dryad, 2022, doi:10.5061/dryad.rfj6q57ds.","short":"I. Tomanek, C.C. Guet, (2022).","ista":"Tomanek I, Guet CC. 2022. Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose, Dryad, 10.5061/dryad.rfj6q57ds.","apa":"Tomanek, I., & Guet, C. C. (2022). Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose. Dryad. https://doi.org/10.5061/dryad.rfj6q57ds","ieee":"I. Tomanek and C. C. Guet, “Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose.” Dryad, 2022.","ama":"Tomanek I, Guet CC. Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose. 2022. doi:10.5061/dryad.rfj6q57ds"},"main_file_link":[{"open_access":"1","url":"https://doi.org/10.5061/dryad.rfj6q57ds"}],"date_published":"2022-12-23T00:00:00Z","doi":"10.5061/dryad.rfj6q57ds","type":"research_data_reference","abstract":[{"text":"Copy-number and point mutations form the basis for most evolutionary novelty through the process of gene duplication and divergence. While a plethora of genomic sequence data reveals the long-term fate of diverging coding sequences and their cis-regulatory elements, little is known about the early dynamics around the duplication event itself. In microorganisms, selection for increased gene expression often drives the expansion of gene copy-number mutations, which serves as a crude adaptation, prior to divergence through refining point mutations. Using a simple synthetic genetic system that allows us to distinguish copy-number and point mutations, we study their early and transient adaptive dynamics in real-time in Escherichia coli. We find two qualitatively different routes of adaptation depending on the level of functional improvement selected for: In conditions of high gene expression demand, the two types of mutations occur as a combination. Under low gene expression demand, negative epistasis between the two types of mutations renders them mutually exclusive. Thus, owing to their higher frequency, adaptation is dominated by copy-number mutations. Ultimately, due to high rates of reversal and pleiotropic cost, copy-number mutations may not only serve as a crude and transient adaptation but also constrain sequence divergence over evolutionary time scales.","lang":"eng"}],"_id":"12339","year":"2022","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"CaGu"}],"publisher":"Dryad","title":"Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose","ddc":["570"],"status":"public","related_material":{"record":[{"relation":"used_in_publication","status":"public","id":"12333"}]},"author":[{"id":"3981F020-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6197-363X","first_name":"Isabella","last_name":"Tomanek","full_name":"Tomanek, Isabella"},{"orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C","full_name":"Guet, Calin C"}],"oa_version":"Published Version","date_updated":"2023-08-03T14:23:06Z","date_created":"2023-01-23T09:00:37Z"},{"scopus_import":"1","article_processing_charge":"No","has_accepted_license":"1","day":"14","citation":{"short":"R. Römhild, D.I. Andersson, PLoS Pathogens 17 (2021).","mla":"Römhild, Roderich, and Dan I. Andersson. “Mechanisms and Therapeutic Potential of Collateral Sensitivity to Antibiotics.” PLoS Pathogens, vol. 17, no. 1, e1009172, Public Library of Science, 2021, doi:10.1371/journal.ppat.1009172.","chicago":"Römhild, Roderich, and Dan I. Andersson. “Mechanisms and Therapeutic Potential of Collateral Sensitivity to Antibiotics.” PLoS Pathogens. Public Library of Science, 2021. https://doi.org/10.1371/journal.ppat.1009172.","ama":"Römhild R, Andersson DI. Mechanisms and therapeutic potential of collateral sensitivity to antibiotics. PLoS Pathogens. 2021;17(1). doi:10.1371/journal.ppat.1009172","apa":"Römhild, R., & Andersson, D. I. (2021). Mechanisms and therapeutic potential of collateral sensitivity to antibiotics. PLoS Pathogens. Public Library of Science. https://doi.org/10.1371/journal.ppat.1009172","ieee":"R. Römhild and D. I. Andersson, “Mechanisms and therapeutic potential of collateral sensitivity to antibiotics,” PLoS Pathogens, vol. 17, no. 1. Public Library of Science, 2021.","ista":"Römhild R, Andersson DI. 2021. Mechanisms and therapeutic potential of collateral sensitivity to antibiotics. PLoS Pathogens. 17(1), e1009172."},"publication":"PLoS Pathogens","article_type":"original","date_published":"2021-01-14T00:00:00Z","type":"journal_article","issue":"1","_id":"9046","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","intvolume":" 17","status":"public","ddc":["570"],"title":"Mechanisms and therapeutic potential of collateral sensitivity to antibiotics","oa_version":"Published Version","file":[{"access_level":"open_access","file_name":"2021_PlosPathogens_Roemhild.pdf","creator":"dernst","file_size":570066,"content_type":"application/pdf","file_id":"9070","relation":"main_file","success":1,"checksum":"d745d7f8fcbb9b95fea16a36f94dee31","date_created":"2021-02-03T12:13:03Z","date_updated":"2021-02-03T12:13:03Z"}],"publication_identifier":{"eissn":["15537374"],"issn":["15537366"]},"month":"01","external_id":{"isi":["000610190400007"],"pmid":["33444399"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"isi":1,"quality_controlled":"1","doi":"10.1371/journal.ppat.1009172","language":[{"iso":"eng"}],"article_number":"e1009172","file_date_updated":"2021-02-03T12:13:03Z","pmid":1,"acknowledgement":"Our work was supported by the Swedish Research Council (grant 2017-01527) to DIA","year":"2021","publisher":"Public Library of Science","department":[{"_id":"CaGu"}],"publication_status":"published","author":[{"full_name":"Römhild, Roderich","first_name":"Roderich","last_name":"Römhild","id":"68E56E44-62B0-11EA-B963-444F3DDC885E","orcid":"0000-0001-9480-5261"},{"full_name":"Andersson, Dan I.","first_name":"Dan I.","last_name":"Andersson"}],"volume":17,"date_updated":"2023-08-07T13:36:55Z","date_created":"2021-01-31T23:01:21Z"},{"abstract":[{"text":"Gene expression is regulated by the set of transcription factors (TFs) that bind to the promoter. The ensuing regulating function is often represented as a combinational logic circuit, where output (gene expression) is determined by current input values (promoter bound TFs) only. However, the simultaneous arrival of TFs is a strong assumption, since transcription and translation of genes introduce intrinsic time delays and there is no global synchronisation among the arrival times of different molecular species at their targets. We present an experimentally implementable genetic circuit with two inputs and one output, which in the presence of small delays in input arrival, exhibits qualitatively distinct population-level phenotypes, over timescales that are longer than typical cell doubling times. From a dynamical systems point of view, these phenotypes represent long-lived transients: although they converge to the same value eventually, they do so after a very long time span. The key feature of this toy model genetic circuit is that, despite having only two inputs and one output, it is regulated by twenty-three distinct DNA-TF configurations, two of which are more stable than others (DNA looped states), one promoting and another blocking the expression of the output gene. Small delays in input arrival time result in a majority of cells in the population quickly reaching the stable state associated with the first input, while exiting of this stable state occurs at a slow timescale. In order to mechanistically model the behaviour of this genetic circuit, we used a rule-based modelling language, and implemented a grid-search to find parameter combinations giving rise to long-lived transients. Our analysis shows that in the absence of feedback, there exist path-dependent gene regulatory mechanisms based on the long timescale of transients. The behaviour of this toy model circuit suggests that gene regulatory networks can exploit event timing to create phenotypes, and it opens the possibility that they could use event timing to memorise events, without regulatory feedback. The model reveals the importance of (i) mechanistically modelling the transitions between the different DNA-TF states, and (ii) employing transient analysis thereof.","lang":"eng"}],"type":"journal_article","oa_version":"Published Version","file":[{"relation":"main_file","file_id":"11364","checksum":"d3aef34cfb13e53bba4cf44d01680793","success":1,"date_updated":"2022-05-12T12:13:27Z","date_created":"2022-05-12T12:13:27Z","access_level":"open_access","file_name":"2021_TheoreticalComputerScience_Petrov.pdf","file_size":2566504,"content_type":"application/pdf","creator":"dernst"}],"status":"public","ddc":["004"],"title":"Long lived transients in gene regulation","intvolume":" 893","_id":"9647","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","day":"04","article_processing_charge":"No","has_accepted_license":"1","scopus_import":"1","date_published":"2021-06-04T00:00:00Z","article_type":"original","page":"1-16","publication":"Theoretical Computer Science","citation":{"apa":"Petrov, T., Igler, C., Sezgin, A., Henzinger, T. A., & Guet, C. C. (2021). Long lived transients in gene regulation. Theoretical Computer Science. Elsevier. https://doi.org/10.1016/j.tcs.2021.05.023","ieee":"T. Petrov, C. Igler, A. Sezgin, T. A. Henzinger, and C. C. Guet, “Long lived transients in gene regulation,” Theoretical Computer Science, vol. 893. Elsevier, pp. 1–16, 2021.","ista":"Petrov T, Igler C, Sezgin A, Henzinger TA, Guet CC. 2021. Long lived transients in gene regulation. Theoretical Computer Science. 893, 1–16.","ama":"Petrov T, Igler C, Sezgin A, Henzinger TA, Guet CC. Long lived transients in gene regulation. Theoretical Computer Science. 2021;893:1-16. doi:10.1016/j.tcs.2021.05.023","chicago":"Petrov, Tatjana, Claudia Igler, Ali Sezgin, Thomas A Henzinger, and Calin C Guet. “Long Lived Transients in Gene Regulation.” Theoretical Computer Science. Elsevier, 2021. https://doi.org/10.1016/j.tcs.2021.05.023.","short":"T. Petrov, C. Igler, A. Sezgin, T.A. Henzinger, C.C. Guet, Theoretical Computer Science 893 (2021) 1–16.","mla":"Petrov, Tatjana, et al. “Long Lived Transients in Gene Regulation.” Theoretical Computer Science, vol. 893, Elsevier, 2021, pp. 1–16, doi:10.1016/j.tcs.2021.05.023."},"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","file_date_updated":"2022-05-12T12:13:27Z","date_created":"2021-07-11T22:01:18Z","date_updated":"2023-08-10T14:11:19Z","volume":893,"author":[{"last_name":"Petrov","first_name":"Tatjana","full_name":"Petrov, Tatjana"},{"id":"46613666-F248-11E8-B48F-1D18A9856A87","first_name":"Claudia","last_name":"Igler","full_name":"Igler, Claudia"},{"id":"4C7638DA-F248-11E8-B48F-1D18A9856A87","last_name":"Sezgin","first_name":"Ali","full_name":"Sezgin, Ali"},{"full_name":"Henzinger, Thomas A","id":"40876CD8-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2985-7724","first_name":"Thomas A","last_name":"Henzinger"},{"first_name":"Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C"}],"publication_status":"published","department":[{"_id":"ToHe"},{"_id":"CaGu"}],"publisher":"Elsevier","year":"2021","acknowledgement":"Tatjana Petrov’s research was supported in part by SNSF Advanced Postdoctoral Mobility Fellowship grant number P300P2 161067, the Ministry of Science, Research and the Arts of the state of Baden-Wurttemberg, and the DFG Centre of Excellence 2117 ‘Centre for the Advanced Study of Collective Behaviour’ (ID: 422037984). Claudia Igler is the recipient of a DOC Fellowship of the Austrian Academy of Sciences. Thomas A. Henzinger’s research was supported in part by the Austrian Science Fund (FWF) under grant Z211-N23 (Wittgenstein Award).","month":"06","publication_identifier":{"issn":["0304-3975"]},"language":[{"iso":"eng"}],"doi":"10.1016/j.tcs.2021.05.023","quality_controlled":"1","isi":1,"project":[{"name":"The Wittgenstein Prize","call_identifier":"FWF","grant_number":"Z211","_id":"25F42A32-B435-11E9-9278-68D0E5697425"}],"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"external_id":{"isi":["000710180500002"]},"oa":1},{"file_date_updated":"2021-08-09T09:44:03Z","ec_funded":1,"publication_status":"published","publisher":"American Chemical Society","department":[{"_id":"MiSi"},{"_id":"GaTk"},{"_id":"Bio"},{"_id":"CaGu"}],"acknowledgement":"We would like to thank Charlott Leu for the production of our chromium wafers, Louise Ritter for her contribution of the IF stainings in Figure 4, Shokoufeh Teymouri for her help with the Bioinert coated slides, and finally Prof. Dr. Joachim Rädler for his valuable scientific guidance.","year":"2021","pmid":1,"date_created":"2021-08-08T22:01:28Z","date_updated":"2023-08-10T14:22:48Z","volume":13,"author":[{"full_name":"Zisis, Themistoklis","first_name":"Themistoklis","last_name":"Zisis"},{"id":"346C1EC6-F248-11E8-B48F-1D18A9856A87","first_name":"Jan","last_name":"Schwarz","full_name":"Schwarz, Jan"},{"full_name":"Balles, Miriam","first_name":"Miriam","last_name":"Balles"},{"last_name":"Kretschmer","first_name":"Maibritt","full_name":"Kretschmer, Maibritt"},{"full_name":"Nemethova, Maria","id":"34E27F1C-F248-11E8-B48F-1D18A9856A87","last_name":"Nemethova","first_name":"Maria"},{"full_name":"Chait, Remy P","first_name":"Remy P","last_name":"Chait","id":"3464AE84-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0876-3187"},{"full_name":"Hauschild, Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9843-3522","first_name":"Robert","last_name":"Hauschild"},{"full_name":"Lange, Janina","first_name":"Janina","last_name":"Lange"},{"first_name":"Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C"},{"last_name":"Sixt","first_name":"Michael K","orcid":"0000-0002-4561-241X","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K"},{"full_name":"Zahler, Stefan","last_name":"Zahler","first_name":"Stefan"}],"month":"08","publication_identifier":{"eissn":["19448252"],"issn":["19448244"]},"isi":1,"quality_controlled":"1","project":[{"name":"Cellular navigation along spatial gradients","call_identifier":"H2020","grant_number":"724373","_id":"25FE9508-B435-11E9-9278-68D0E5697425"}],"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"oa":1,"external_id":{"pmid":["34283577"],"isi":["000683741400026"]},"language":[{"iso":"eng"}],"doi":"10.1021/acsami.1c09850","type":"journal_article","abstract":[{"text":"Attachment of adhesive molecules on cell culture surfaces to restrict cell adhesion to defined areas and shapes has been vital for the progress of in vitro research. In currently existing patterning methods, a combination of pattern properties such as stability, precision, specificity, high-throughput outcome, and spatiotemporal control is highly desirable but challenging to achieve. Here, we introduce a versatile and high-throughput covalent photoimmobilization technique, comprising a light-dose-dependent patterning step and a subsequent functionalization of the pattern via click chemistry. This two-step process is feasible on arbitrary surfaces and allows for generation of sustainable patterns and gradients. The method is validated in different biological systems by patterning adhesive ligands on cell-repellent surfaces, thereby constraining the growth and migration of cells to the designated areas. We then implement a sequential photopatterning approach by adding a second switchable patterning step, allowing for spatiotemporal control over two distinct surface patterns. As a proof of concept, we reconstruct the dynamics of the tip/stalk cell switch during angiogenesis. Our results show that the spatiotemporal control provided by our “sequential photopatterning” system is essential for mimicking dynamic biological processes and that our innovative approach has great potential for further applications in cell science.","lang":"eng"}],"issue":"30","ddc":["620","570"],"title":"Sequential and switchable patterning for studying cellular processes under spatiotemporal control","status":"public","intvolume":" 13","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"9822","oa_version":"Published Version","file":[{"creator":"asandaue","content_type":"application/pdf","file_size":7123293,"file_name":"2021_ACSAppliedMaterialsAndInterfaces_Zisis.pdf","access_level":"open_access","date_created":"2021-08-09T09:44:03Z","date_updated":"2021-08-09T09:44:03Z","success":1,"checksum":"b043a91d9f9200e467b970b692687ed3","file_id":"9833","relation":"main_file"}],"scopus_import":"1","day":"04","article_processing_charge":"Yes (in subscription journal)","has_accepted_license":"1","article_type":"original","page":"35545–35560","publication":"ACS Applied Materials and Interfaces","citation":{"ista":"Zisis T, Schwarz J, Balles M, Kretschmer M, Nemethova M, Chait RP, Hauschild R, Lange J, Guet CC, Sixt MK, Zahler S. 2021. Sequential and switchable patterning for studying cellular processes under spatiotemporal control. ACS Applied Materials and Interfaces. 13(30), 35545–35560.","ieee":"T. Zisis et al., “Sequential and switchable patterning for studying cellular processes under spatiotemporal control,” ACS Applied Materials and Interfaces, vol. 13, no. 30. American Chemical Society, pp. 35545–35560, 2021.","apa":"Zisis, T., Schwarz, J., Balles, M., Kretschmer, M., Nemethova, M., Chait, R. P., … Zahler, S. (2021). Sequential and switchable patterning for studying cellular processes under spatiotemporal control. ACS Applied Materials and Interfaces. American Chemical Society. https://doi.org/10.1021/acsami.1c09850","ama":"Zisis T, Schwarz J, Balles M, et al. Sequential and switchable patterning for studying cellular processes under spatiotemporal control. ACS Applied Materials and Interfaces. 2021;13(30):35545–35560. doi:10.1021/acsami.1c09850","chicago":"Zisis, Themistoklis, Jan Schwarz, Miriam Balles, Maibritt Kretschmer, Maria Nemethova, Remy P Chait, Robert Hauschild, et al. “Sequential and Switchable Patterning for Studying Cellular Processes under Spatiotemporal Control.” ACS Applied Materials and Interfaces. American Chemical Society, 2021. https://doi.org/10.1021/acsami.1c09850.","mla":"Zisis, Themistoklis, et al. “Sequential and Switchable Patterning for Studying Cellular Processes under Spatiotemporal Control.” ACS Applied Materials and Interfaces, vol. 13, no. 30, American Chemical Society, 2021, pp. 35545–35560, doi:10.1021/acsami.1c09850.","short":"T. Zisis, J. Schwarz, M. Balles, M. Kretschmer, M. Nemethova, R.P. Chait, R. Hauschild, J. Lange, C.C. Guet, M.K. Sixt, S. Zahler, ACS Applied Materials and Interfaces 13 (2021) 35545–35560."},"date_published":"2021-08-04T00:00:00Z"},{"oa_version":"Published Version","_id":"9746","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","status":"public","title":"High potency of sequential therapy with only beta-lactam antibiotics","intvolume":" 10","abstract":[{"text":"Evolutionary adaptation is a major source of antibiotic resistance in bacterial pathogens. Evolution-informed therapy aims to constrain resistance by accounting for bacterial evolvability. Sequential treatments with antibiotics that target different bacterial processes were previously shown to limit adaptation through genetic resistance trade-offs and negative hysteresis. Treatment with homogeneous sets of antibiotics is generally viewed to be disadvantageous, as it should rapidly lead to cross-resistance. We here challenged this assumption by determining the evolutionary response of Pseudomonas aeruginosa to experimental sequential treatments involving both heterogenous and homogeneous antibiotic sets. To our surprise, we found that fast switching between only β-lactam antibiotics resulted in increased extinction of bacterial populations. We demonstrate that extinction is favored by low rates of spontaneous resistance emergence and low levels of spontaneous cross-resistance among the antibiotics in sequence. The uncovered principles may help to guide the optimized use of available antibiotics in highly potent, evolution-informed treatment designs.","lang":"eng"}],"type":"journal_article","date_published":"2021-07-28T00:00:00Z","publication":"eLife","citation":{"short":"A. Batra, R. Römhild, E. Rousseau, S. Franzenburg, S. Niemann, H. Schulenburg, ELife 10 (2021).","mla":"Batra, Aditi, et al. “High Potency of Sequential Therapy with Only Beta-Lactam Antibiotics.” ELife, vol. 10, e68876, eLife Sciences Publications, 2021, doi:10.7554/elife.68876.","chicago":"Batra, Aditi, Roderich Römhild, Emilie Rousseau, Sören Franzenburg, Stefan Niemann, and Hinrich Schulenburg. “High Potency of Sequential Therapy with Only Beta-Lactam Antibiotics.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/elife.68876.","ama":"Batra A, Römhild R, Rousseau E, Franzenburg S, Niemann S, Schulenburg H. High potency of sequential therapy with only beta-lactam antibiotics. eLife. 2021;10. doi:10.7554/elife.68876","ieee":"A. Batra, R. Römhild, E. Rousseau, S. Franzenburg, S. Niemann, and H. Schulenburg, “High potency of sequential therapy with only beta-lactam antibiotics,” eLife, vol. 10. eLife Sciences Publications, 2021.","apa":"Batra, A., Römhild, R., Rousseau, E., Franzenburg, S., Niemann, S., & Schulenburg, H. (2021). High potency of sequential therapy with only beta-lactam antibiotics. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.68876","ista":"Batra A, Römhild R, Rousseau E, Franzenburg S, Niemann S, Schulenburg H. 2021. High potency of sequential therapy with only beta-lactam antibiotics. eLife. 10, e68876."},"article_type":"original","day":"28","article_processing_charge":"No","scopus_import":"1","author":[{"full_name":"Batra, Aditi","last_name":"Batra","first_name":"Aditi"},{"full_name":"Römhild, Roderich","orcid":"0000-0001-9480-5261","id":"68E56E44-62B0-11EA-B963-444F3DDC885E","last_name":"Römhild","first_name":"Roderich"},{"full_name":"Rousseau, Emilie","first_name":"Emilie","last_name":"Rousseau"},{"full_name":"Franzenburg, Sören","last_name":"Franzenburg","first_name":"Sören"},{"first_name":"Stefan","last_name":"Niemann","full_name":"Niemann, Stefan"},{"full_name":"Schulenburg, Hinrich","last_name":"Schulenburg","first_name":"Hinrich"}],"date_created":"2021-07-28T13:36:57Z","date_updated":"2023-08-11T10:26:29Z","volume":10,"year":"2021","acknowledgement":"We would like to thank Leif Tueffers and João Botelho for discussions and suggestions as well as Kira Haas and Julia Bunk for technical support. We acknowledge financial support from the German Science Foundation (grant SCHU 1415/12-2 to HS, and funding under Germany’s Excellence Strategy EXC 2167–390884018 as well as the Research Training Group 2501 TransEvo to HS and SN), the Max Planck Society (IMPRS scholarship to AB; Max-Planck fellowship to HS), and the Leibniz Science Campus Evolutionary Medicine of the Lung (EvoLUNG, to HS and SN). This work was further supported by the German Science Foundation Research Infrastructure NGS_CC (project 407495230) as part of the Next Generation Sequencing Competence Network (project 423957469). NGS analyses were carried out at the Competence Centre for Genomic Analysis Kiel (CCGA Kiel).","pmid":1,"publication_status":"published","publisher":"eLife Sciences Publications","department":[{"_id":"CaGu"}],"article_number":"e68876","doi":"10.7554/elife.68876","language":[{"iso":"eng"}],"external_id":{"isi":["000692027800001"],"pmid":["34318749"]},"main_file_link":[{"open_access":"1","url":"https://doi.org/10.7554/eLife.68876"}],"oa":1,"quality_controlled":"1","isi":1,"month":"07","publication_identifier":{"eissn":["2050-084X"]}},{"scopus_import":"1","day":"01","article_processing_charge":"No","publication":"Protein Engineering, Design and Selection","citation":{"ama":"Lee J, Vernet A, Gruber N, et al. Rational engineering of an erythropoietin fusion protein to treat hypoxia. Protein Engineering, Design and Selection. 2021;34. doi:10.1093/protein/gzab025","apa":"Lee, J., Vernet, A., Gruber, N., Kready, K. M., Burrill, D. R., Way, J. C., & Silver, P. A. (2021). Rational engineering of an erythropoietin fusion protein to treat hypoxia. Protein Engineering, Design and Selection. Oxford University Press. https://doi.org/10.1093/protein/gzab025","ieee":"J. Lee et al., “Rational engineering of an erythropoietin fusion protein to treat hypoxia,” Protein Engineering, Design and Selection, vol. 34. Oxford University Press, 2021.","ista":"Lee J, Vernet A, Gruber N, Kready KM, Burrill DR, Way JC, Silver PA. 2021. Rational engineering of an erythropoietin fusion protein to treat hypoxia. Protein Engineering, Design and Selection. 34, gzab025.","short":"J. Lee, A. Vernet, N. Gruber, K.M. Kready, D.R. Burrill, J.C. Way, P.A. Silver, Protein Engineering, Design and Selection 34 (2021).","mla":"Lee, Jungmin, et al. “Rational Engineering of an Erythropoietin Fusion Protein to Treat Hypoxia.” Protein Engineering, Design and Selection, vol. 34, gzab025, Oxford University Press, 2021, doi:10.1093/protein/gzab025.","chicago":"Lee, Jungmin, Andyna Vernet, Nathalie Gruber, Kasia M. Kready, Devin R. Burrill, Jeffrey C. Way, and Pamela A. Silver. “Rational Engineering of an Erythropoietin Fusion Protein to Treat Hypoxia.” Protein Engineering, Design and Selection. Oxford University Press, 2021. https://doi.org/10.1093/protein/gzab025."},"article_type":"original","date_published":"2021-11-01T00:00:00Z","type":"journal_article","abstract":[{"lang":"eng","text":"Erythropoietin enhances oxygen delivery and reduces hypoxia-induced cell death, but its pro-thrombotic activity is problematic for use of erythropoietin in treating hypoxia. We constructed a fusion protein that stimulates red blood cell production and neuroprotection without triggering platelet production, a marker for thrombosis. The protein consists of an anti-glycophorin A nanobody and an erythropoietin mutant (L108A). The mutation reduces activation of erythropoietin receptor homodimers that induce erythropoiesis and thrombosis, but maintains the tissue-protective signaling. The binding of the nanobody element to glycophorin A rescues homodimeric erythropoietin receptor activation on red blood cell precursors. In a cell proliferation assay, the fusion protein is active at 10−14 M, allowing an estimate of the number of receptor–ligand complexes needed for signaling. This fusion protein stimulates erythroid cell proliferation in vitro and in mice, and shows neuroprotective activity in vitro. Our erythropoietin fusion protein presents a novel molecule for treating hypoxia."}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"10363","status":"public","title":"Rational engineering of an erythropoietin fusion protein to treat hypoxia","intvolume":" 34","oa_version":"Published Version","month":"11","publication_identifier":{"issn":["1741-0126"],"eissn":["1741-0134"]},"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1093/protein/gzab025"}],"oa":1,"external_id":{"isi":["000746596900001"],"pmid":["34725710"]},"quality_controlled":"1","isi":1,"doi":"10.1093/protein/gzab025","language":[{"iso":"eng"}],"article_number":"gzab025","year":"2021","acknowledgement":"This work was supported by funds from the Wyss Institute for Biologically Inspired Engineering and the Boston Biomedical Innovation Center (Pilot Award 112475; Drive Award U54HL119145). J.L., K.M.K., D.R.B., J.C.W. and P.A.S. were supported by the Harvard Medical School Department of Systems Biology. J.C.W. was further supported by the Harvard Medical School Laboratory of Systems Pharmacology. A.V., D.R.B. and P.A.S. were further supported by the Wyss Institute for Biologically Inspired Engineering. N.G.G. was sponsored by the Army Research Office under Grant Number W911NF-17-2-0092. The views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the Army Research Office or the U.S. Government. The U.S. Government is authorized to reproduce and distribute reprints for Government purposes notwithstanding any copyright notation herein. We sincerely thank Amanda Graveline and the Wyss Institute at Harvard for their scientific support.","pmid":1,"publication_status":"published","publisher":"Oxford University Press","department":[{"_id":"CaGu"}],"author":[{"full_name":"Lee, Jungmin","first_name":"Jungmin","last_name":"Lee"},{"full_name":"Vernet, Andyna","last_name":"Vernet","first_name":"Andyna"},{"full_name":"Gruber, Nathalie","id":"2C9C8316-AA17-11E9-B5C2-8BC2E5697425","last_name":"Gruber","first_name":"Nathalie"},{"last_name":"Kready","first_name":"Kasia M.","full_name":"Kready, Kasia M."},{"last_name":"Burrill","first_name":"Devin R.","full_name":"Burrill, Devin R."},{"last_name":"Way","first_name":"Jeffrey C.","full_name":"Way, Jeffrey C."},{"full_name":"Silver, Pamela A.","first_name":"Pamela A.","last_name":"Silver"}],"date_updated":"2023-08-14T13:01:38Z","date_created":"2021-11-28T23:01:28Z","volume":34},{"language":[{"iso":"eng"}],"doi":"10.7554/elife.65993","quality_controlled":"1","isi":1,"project":[{"name":"The Systems Biology of Transcriptional Read-Through in Bacteria: from Synthetic Networks to Genomic Studies","call_identifier":"FP7","_id":"2517526A-B435-11E9-9278-68D0E5697425","grant_number":"628377"},{"_id":"268BFA92-B435-11E9-9278-68D0E5697425","grant_number":"I03901","call_identifier":"FWF","name":"CyberCircuits: Cybergenetic circuits to test composability of gene networks"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"external_id":{"isi":["000631050900001"]},"month":"03","publication_identifier":{"issn":["2050-084X"]},"date_created":"2021-03-23T10:11:46Z","date_updated":"2024-02-21T12:41:57Z","volume":10,"author":[{"id":"3ABC5BA6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1391-8377","first_name":"Anna A","last_name":"Nagy-Staron","full_name":"Nagy-Staron, Anna A"},{"full_name":"Tomasek, Kathrin","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3768-877X","first_name":"Kathrin","last_name":"Tomasek"},{"full_name":"Caruso Carter, Caroline","last_name":"Caruso Carter","first_name":"Caroline"},{"first_name":"Elisabeth","last_name":"Sonnleitner","full_name":"Sonnleitner, Elisabeth"},{"last_name":"Kavcic","first_name":"Bor","orcid":"0000-0001-6041-254X","id":"350F91D2-F248-11E8-B48F-1D18A9856A87","full_name":"Kavcic, Bor"},{"full_name":"Paixão, Tiago","first_name":"Tiago","last_name":"Paixão"},{"last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C"}],"related_material":{"record":[{"relation":"research_data","status":"public","id":"8951"}]},"publication_status":"published","publisher":"eLife Sciences Publications","department":[{"_id":"GaTk"},{"_id":"CaGu"}],"acknowledgement":"We thank J Bollback, L Hurst, M Lagator, C Nizak, O Rivoire, M Savageau, G Tkacik, and B Vicozo\r\nfor helpful discussions; A Dolinar and A Greshnova for technical assistance; T Bollenbach for supplying the strain JW0336; C Rusnac, and members of the Guet lab for comments. The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement n˚\r\n628377 (ANS) and an Austrian Science Fund (FWF) grant n˚ I 3901-B32 (CCG).","year":"2021","file_date_updated":"2021-03-23T10:12:58Z","ec_funded":1,"article_number":"e65993","date_published":"2021-03-08T00:00:00Z","article_type":"original","publication":"eLife","citation":{"ama":"Nagy-Staron AA, Tomasek K, Caruso Carter C, et al. Local genetic context shapes the function of a gene regulatory network. eLife. 2021;10. doi:10.7554/elife.65993","ista":"Nagy-Staron AA, Tomasek K, Caruso Carter C, Sonnleitner E, Kavcic B, Paixão T, Guet CC. 2021. Local genetic context shapes the function of a gene regulatory network. eLife. 10, e65993.","apa":"Nagy-Staron, A. A., Tomasek, K., Caruso Carter, C., Sonnleitner, E., Kavcic, B., Paixão, T., & Guet, C. C. (2021). Local genetic context shapes the function of a gene regulatory network. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.65993","ieee":"A. A. Nagy-Staron et al., “Local genetic context shapes the function of a gene regulatory network,” eLife, vol. 10. eLife Sciences Publications, 2021.","mla":"Nagy-Staron, Anna A., et al. “Local Genetic Context Shapes the Function of a Gene Regulatory Network.” ELife, vol. 10, e65993, eLife Sciences Publications, 2021, doi:10.7554/elife.65993.","short":"A.A. Nagy-Staron, K. Tomasek, C. Caruso Carter, E. Sonnleitner, B. Kavcic, T. Paixão, C.C. Guet, ELife 10 (2021).","chicago":"Nagy-Staron, Anna A, Kathrin Tomasek, Caroline Caruso Carter, Elisabeth Sonnleitner, Bor Kavcic, Tiago Paixão, and Calin C Guet. “Local Genetic Context Shapes the Function of a Gene Regulatory Network.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/elife.65993."},"day":"08","article_processing_charge":"Yes","has_accepted_license":"1","keyword":["Genetics and Molecular Biology"],"oa_version":"Published Version","file":[{"creator":"bkavcic","file_size":1390469,"content_type":"application/pdf","access_level":"open_access","file_name":"elife-65993-v2.pdf","success":1,"checksum":"3c2f44058c2dd45a5a1027f09d263f8e","date_created":"2021-03-23T10:12:58Z","date_updated":"2021-03-23T10:12:58Z","file_id":"9284","relation":"main_file"}],"status":"public","title":"Local genetic context shapes the function of a gene regulatory network","ddc":["570"],"intvolume":" 10","_id":"9283","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","abstract":[{"text":"Gene expression levels are influenced by multiple coexisting molecular mechanisms. Some of these interactions such as those of transcription factors and promoters have been studied extensively. However, predicting phenotypes of gene regulatory networks (GRNs) remains a major challenge. Here, we use a well-defined synthetic GRN to study in Escherichia coli how network phenotypes depend on local genetic context, i.e. the genetic neighborhood of a transcription factor and its relative position. We show that one GRN with fixed topology can display not only quantitatively but also qualitatively different phenotypes, depending solely on the local genetic context of its components. Transcriptional read-through is the main molecular mechanism that places one transcriptional unit (TU) within two separate regulons without the need for complex regulatory sequences. We propose that relative order of individual TUs, with its potential for combinatorial complexity, plays an important role in shaping phenotypes of GRNs.","lang":"eng"}],"type":"journal_article"},{"has_accepted_license":"1","article_processing_charge":"No","day":"18","date_published":"2021-11-18T00:00:00Z","page":"73","citation":{"ama":"Tomasek K. Pathogenic Escherichia coli hijack the host immune response. 2021. doi:10.15479/at:ista:10307","apa":"Tomasek, K. (2021). Pathogenic Escherichia coli hijack the host immune response. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:10307","ieee":"K. Tomasek, “Pathogenic Escherichia coli hijack the host immune response,” Institute of Science and Technology Austria, 2021.","ista":"Tomasek K. 2021. Pathogenic Escherichia coli hijack the host immune response. Institute of Science and Technology Austria.","short":"K. Tomasek, Pathogenic Escherichia Coli Hijack the Host Immune Response, Institute of Science and Technology Austria, 2021.","mla":"Tomasek, Kathrin. Pathogenic Escherichia Coli Hijack the Host Immune Response. Institute of Science and Technology Austria, 2021, doi:10.15479/at:ista:10307.","chicago":"Tomasek, Kathrin. “Pathogenic Escherichia Coli Hijack the Host Immune Response.” Institute of Science and Technology Austria, 2021. https://doi.org/10.15479/at:ista:10307."},"abstract":[{"text":"Bacteria-host interactions represent a continuous trade-off between benefit and risk. Thus, the host immune response is faced with a non-trivial problem – accommodate beneficial commensals and remove harmful pathogens. This is especially difficult as molecular patterns, such as lipopolysaccharide or specific surface organelles such as pili, are conserved in both, commensal and pathogenic bacteria. Type 1 pili, tightly regulated by phase variation, are considered an important virulence factor of pathogenic bacteria as they facilitate invasion into host cells. While invasion represents a de facto passive mechanism for pathogens to escape the host immune response, we demonstrate a fundamental role of type 1 pili as active modulators of the innate and adaptive immune response.","lang":"eng"}],"alternative_title":["ISTA Thesis"],"type":"dissertation","oa_version":"Published Version","file":[{"file_name":"ThesisTomasekKathrin.pdf","access_level":"open_access","creator":"ktomasek","content_type":"application/pdf","file_size":13266088,"embargo":"2022-11-18","file_id":"10308","relation":"main_file","date_updated":"2022-12-20T23:30:05Z","date_created":"2021-11-18T15:07:31Z","checksum":"b39c9e0ef18d0484d537a67551effd02"},{"file_id":"10309","relation":"source_file","date_created":"2021-11-18T15:07:46Z","date_updated":"2022-12-20T23:30:05Z","checksum":"c0c440ee9e5ef1102a518a4f9f023e7c","file_name":"ThesisTomasekKathrin.docx","embargo_to":"open_access","access_level":"closed","creator":"ktomasek","file_size":7539509,"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document"}],"title":"Pathogenic Escherichia coli hijack the host immune response","status":"public","ddc":["570"],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"10307","publication_identifier":{"issn":["2663-337X"]},"month":"11","language":[{"iso":"eng"}],"supervisor":[{"full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4561-241X","first_name":"Michael K","last_name":"Sixt"},{"full_name":"Guet, Calin C","first_name":"Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052"}],"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"degree_awarded":"PhD","doi":"10.15479/at:ista:10307","oa":1,"file_date_updated":"2022-12-20T23:30:05Z","date_created":"2021-11-18T15:05:06Z","date_updated":"2023-09-07T13:34:38Z","related_material":{"record":[{"id":"10316","status":"public","relation":"part_of_dissertation"}]},"author":[{"full_name":"Tomasek, Kathrin","last_name":"Tomasek","first_name":"Kathrin","orcid":"0000-0003-3768-877X","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87"}],"publisher":"Institute of Science and Technology Austria","department":[{"_id":"MiSi"},{"_id":"CaGu"},{"_id":"GradSch"}],"publication_status":"published","year":"2021"},{"ec_funded":1,"abstract":[{"text":"A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on dendritic cells as a previously undescribed binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of pathogenic bacteria to CD14 lead to reduced dendritic cell migration and blunted expression of co-stimulatory molecules, both rate-limiting factors of T cell activation. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease.","lang":"eng"}],"type":"preprint","related_material":{"record":[{"id":"11843","relation":"later_version","status":"public"},{"status":"public","relation":"dissertation_contains","id":"10307"}]},"author":[{"full_name":"Tomasek, Kathrin","first_name":"Kathrin","last_name":"Tomasek","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3768-877X"},{"full_name":"Leithner, Alexander F","last_name":"Leithner","first_name":"Alexander F","orcid":"0000-0002-1073-744X","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87"},{"id":"727b3c7d-4939-11ec-89b3-b9b0750ab74d","last_name":"Glatzová","first_name":"Ivana","full_name":"Glatzová, Ivana"},{"last_name":"Lukesch","first_name":"Michael S.","full_name":"Lukesch, Michael S."},{"last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C"},{"orcid":"0000-0002-4561-241X","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K","full_name":"Sixt, Michael K"}],"oa_version":"Preprint","date_updated":"2024-03-28T23:30:35Z","date_created":"2021-11-19T12:24:16Z","_id":"10316","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","year":"2021","acknowledgement":"We thank Ulrich Dobrindt for providing UPEC strain CFT073, Vlad Gavra and Maximilian Götz, Bor Kavčič, Jonna Alanko and Eva Kiermaier for help with experiments and Robert Hauschild, Julian Stopp and Saren Tasciyan for help with data analysis. We thank the IST Austria Scientific Service Units, especially the Bioimaging facility, the Preclinical facility and the Electron microscopy facility for technical support, Jakob Wallner and all members of the Guet and Sixt lab for fruitful discussions and Daria Siekhaus for critically reading the manuscript. This work was supported by grants from the Austrian Research Promotion Agency (FEMtech 868984) to I.G., the European Research Council (CoG 724373) and the Austrian Science Fund (FWF P29911) to M.S.","department":[{"_id":"CaGu"},{"_id":"MiSi"}],"publisher":"Cold Spring Harbor Laboratory","status":"public","publication_status":"submitted","title":"Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14","article_processing_charge":"No","day":"18","month":"10","date_published":"2021-10-18T00:00:00Z","doi":"10.1101/2021.10.18.464770","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"citation":{"chicago":"Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch, Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2021.10.18.464770.","short":"K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt, BioRxiv (n.d.).","mla":"Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2021.10.18.464770.","ieee":"K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M. K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14,” bioRxiv. Cold Spring Harbor Laboratory.","apa":"Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., & Sixt, M. K. (n.d.). Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2021.10.18.464770","ista":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. bioRxiv, 10.1101/2021.10.18.464770.","ama":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. bioRxiv. doi:10.1101/2021.10.18.464770"},"oa":1,"main_file_link":[{"open_access":"1","url":"https://www.biorxiv.org/content/10.1101/2021.10.18.464770v1"}],"publication":"bioRxiv","project":[{"_id":"25FE9508-B435-11E9-9278-68D0E5697425","grant_number":"724373","name":"Cellular navigation along spatial gradients","call_identifier":"H2020"},{"_id":"26018E70-B435-11E9-9278-68D0E5697425","grant_number":"P29911","call_identifier":"FWF","name":"Mechanical adaptation of lamellipodial actin"}]},{"month":"07","day":"11","article_processing_charge":"No","publication_identifier":{"eisbn":["9781071607558"],"eissn":["19406029"]},"scopus_import":"1","series_title":"MIMB","doi":"10.1007/978-1-0716-0755-8_16","date_published":"2020-07-11T00:00:00Z","language":[{"iso":"eng"}],"publication":"Photoswitching Proteins","citation":{"ama":"Kainrath S, Janovjak HL. Design and application of light-regulated receptor tyrosine kinases. In: Niopek D, ed. Photoswitching Proteins. Vol 2173. MIMB. Springer Nature; 2020:233-246. doi:10.1007/978-1-0716-0755-8_16","ieee":"S. Kainrath and H. L. Janovjak, “Design and application of light-regulated receptor tyrosine kinases,” in Photoswitching Proteins, vol. 2173, D. Niopek, Ed. Springer Nature, 2020, pp. 233–246.","apa":"Kainrath, S., & Janovjak, H. L. (2020). Design and application of light-regulated receptor tyrosine kinases. In D. Niopek (Ed.), Photoswitching Proteins (Vol. 2173, pp. 233–246). Springer Nature. https://doi.org/10.1007/978-1-0716-0755-8_16","ista":"Kainrath S, Janovjak HL. 2020.Design and application of light-regulated receptor tyrosine kinases. In: Photoswitching Proteins. Methods in Molecular Biology, vol. 2173, 233–246.","short":"S. Kainrath, H.L. Janovjak, in:, D. Niopek (Ed.), Photoswitching Proteins, Springer Nature, 2020, pp. 233–246.","mla":"Kainrath, Stephanie, and Harald L. Janovjak. “Design and Application of Light-Regulated Receptor Tyrosine Kinases.” Photoswitching Proteins, edited by Dominik Niopek, vol. 2173, Springer Nature, 2020, pp. 233–46, doi:10.1007/978-1-0716-0755-8_16.","chicago":"Kainrath, Stephanie, and Harald L Janovjak. “Design and Application of Light-Regulated Receptor Tyrosine Kinases.” In Photoswitching Proteins, edited by Dominik Niopek, 2173:233–46. MIMB. Springer Nature, 2020. https://doi.org/10.1007/978-1-0716-0755-8_16."},"page":"233-246","abstract":[{"lang":"eng","text":"Understanding how the activity of membrane receptors and cellular signaling pathways shapes cell behavior is of fundamental interest in basic and applied research. Reengineering receptors to react to light instead of their cognate ligands allows for generating defined signaling inputs with high spatial and temporal precision and facilitates the dissection of complex signaling networks. Here, we describe fundamental considerations in the design of light-regulated receptor tyrosine kinases (Opto-RTKs) and appropriate control experiments. We also introduce methods for transient receptor expression in HEK293 cells, quantitative assessment of signaling activity in reporter gene assays, semiquantitative assessment of (in)activation time courses through Western blot (WB) analysis, and easy to implement light stimulation hardware."}],"type":"book_chapter","alternative_title":["Methods in Molecular Biology"],"author":[{"full_name":"Kainrath, Stephanie","id":"32CFBA64-F248-11E8-B48F-1D18A9856A87","first_name":"Stephanie","last_name":"Kainrath"},{"full_name":"Janovjak, Harald L","orcid":"0000-0002-8023-9315","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","last_name":"Janovjak","first_name":"Harald L"}],"date_updated":"2021-01-12T08:17:17Z","date_created":"2020-07-26T22:01:03Z","volume":2173,"oa_version":"None","_id":"8173","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","year":"2020","publication_status":"published","title":"Design and application of light-regulated receptor tyrosine kinases","status":"public","intvolume":" 2173","publisher":"Springer Nature","department":[{"_id":"CaGu"}],"editor":[{"full_name":"Niopek, Dominik","last_name":"Niopek","first_name":"Dominik"}]},{"citation":{"short":"R. Grah, Gene Regulation across Scales – How Biophysical Constraints Shape Evolution, Institute of Science and Technology Austria, 2020.","mla":"Grah, Rok. Gene Regulation across Scales – How Biophysical Constraints Shape Evolution. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8155.","chicago":"Grah, Rok. “Gene Regulation across Scales – How Biophysical Constraints Shape Evolution.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8155.","ama":"Grah R. Gene regulation across scales – how biophysical constraints shape evolution. 2020. doi:10.15479/AT:ISTA:8155","apa":"Grah, R. (2020). Gene regulation across scales – how biophysical constraints shape evolution. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8155","ieee":"R. Grah, “Gene regulation across scales – how biophysical constraints shape evolution,” Institute of Science and Technology Austria, 2020.","ista":"Grah R. 2020. Gene regulation across scales – how biophysical constraints shape evolution. Institute of Science and Technology Austria."},"page":"310","date_published":"2020-07-24T00:00:00Z","day":"24","has_accepted_license":"1","article_processing_charge":"No","_id":"8155","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","ddc":["530","570"],"status":"public","title":"Gene regulation across scales – how biophysical constraints shape evolution","file":[{"date_updated":"2020-07-27T12:00:07Z","date_created":"2020-07-27T12:00:07Z","success":1,"relation":"main_file","file_id":"8176","content_type":"application/pdf","file_size":16638998,"creator":"rgrah","file_name":"Thesis_RokGrah_200727_convertedNew.pdf","access_level":"open_access"},{"content_type":"application/zip","file_size":347459978,"creator":"rgrah","access_level":"closed","file_name":"Thesis_new.zip","date_created":"2020-07-27T12:02:23Z","date_updated":"2020-07-30T13:04:55Z","relation":"main_file","file_id":"8177"}],"oa_version":"Published Version","type":"dissertation","alternative_title":["ISTA Thesis"],"abstract":[{"lang":"eng","text":"In the thesis we focus on the interplay of the biophysics and evolution of gene regulation. We start by addressing how the type of prokaryotic gene regulation – activation and repression – affects spurious binding to DNA, also known as\r\ntranscriptional crosstalk. We propose that regulatory interference caused by excess regulatory proteins in the dense cellular medium – global crosstalk – could be a factor in determining which type of gene regulatory network is evolutionarily preferred. Next,we use a normative approach in eukaryotic gene regulation to describe minimal\r\nnon-equilibrium enhancer models that optimize so-called regulatory phenotypes. We find a class of models that differ from standard thermodynamic equilibrium models by a single parameter that notably increases the regulatory performance. Next chapter addresses the question of genotype-phenotype-fitness maps of higher dimensional phenotypes. We show that our biophysically realistic approach allows us to understand how the mechanisms of promoter function constrain genotypephenotype maps, and how they affect the evolutionary trajectories of promoters.\r\nIn the last chapter we ask whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. Using mathematical modeling, we show that amplifications can tune gene expression in many environments, including those where transcription factor-based schemes are\r\nhard to evolve or maintain. "}],"oa":1,"project":[{"name":"Biophysically realistic genotype-phenotype maps for regulatory networks","_id":"267C84F4-B435-11E9-9278-68D0E5697425"}],"doi":"10.15479/AT:ISTA:8155","degree_awarded":"PhD","supervisor":[{"full_name":"Guet, Calin C","last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Tkačik, Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","first_name":"Gašper","last_name":"Tkačik"}],"language":[{"iso":"eng"}],"month":"07","publication_identifier":{"issn":["2663-337X"]},"acknowledgement":"For the duration of his PhD, Rok was a recipient of a DOC fellowship of the Austrian Academy of Sciences.","year":"2020","publication_status":"published","publisher":"Institute of Science and Technology Austria","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"author":[{"last_name":"Grah","first_name":"Rok","orcid":"0000-0003-2539-3560","id":"483E70DE-F248-11E8-B48F-1D18A9856A87","full_name":"Grah, Rok"}],"related_material":{"record":[{"id":"7675","status":"public","relation":"part_of_dissertation"},{"id":"7569","relation":"part_of_dissertation","status":"public"},{"relation":"part_of_dissertation","status":"public","id":"7652"}]},"date_created":"2020-07-23T09:51:28Z","date_updated":"2023-09-07T13:13:27Z","file_date_updated":"2020-07-30T13:04:55Z"},{"abstract":[{"lang":"eng","text":"In prokaryotes, thermodynamic models of gene regulation provide a highly quantitative mapping from promoter sequences to gene expression levels that is compatible with in vivo and in vitro bio-physical measurements. Such concordance has not been achieved for models of enhancer function in eukaryotes. In equilibrium models, it is difficult to reconcile the reported short transcription factor (TF) residence times on the DNA with the high specificity of regulation. In non-equilibrium models, progress is difficult due to an explosion in the number of parameters. Here, we navigate this complexity by looking for minimal non-equilibrium enhancer models that yield desired regulatory phenotypes: low TF residence time, high specificity and tunable cooperativity. We find that a single extra parameter, interpretable as the “linking rate” by which bound TFs interact with Mediator components, enables our models to escape equilibrium bounds and access optimal regulatory phenotypes, while remaining consistent with the reported phenomenology and simple enough to be inferred from upcoming experiments. We further find that high specificity in non-equilibrium models is in a tradeoff with gene expression noise, predicting bursty dynamics — an experimentally-observed hallmark of eukaryotic transcription. By drastically reducing the vast parameter space to a much smaller subspace that optimally realizes biological function prior to inference from data, our normative approach holds promise for mathematical models in systems biology."}],"type":"preprint","date_created":"2020-04-23T10:12:51Z","date_updated":"2023-09-07T13:13:26Z","oa_version":"Preprint","author":[{"first_name":"Rok","last_name":"Grah","id":"483E70DE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2539-3560","full_name":"Grah, Rok"},{"first_name":"Benjamin","last_name":"Zoller","full_name":"Zoller, Benjamin"},{"full_name":"Tkačik, Gašper","first_name":"Gašper","last_name":"Tkačik","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455"}],"related_material":{"record":[{"id":"8155","relation":"dissertation_contains","status":"public"}]},"status":"public","title":"Normative models of enhancer function","publication_status":"published","publisher":"Cold Spring Harbor Laboratory","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"year":"2020","_id":"7675","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","day":"09","month":"04","article_processing_charge":"No","language":[{"iso":"eng"}],"date_published":"2020-04-09T00:00:00Z","doi":"10.1101/2020.04.08.029405","project":[{"name":"Can evolution minimize spurious signaling crosstalk to reach optimal performance?","_id":"2665AAFE-B435-11E9-9278-68D0E5697425","grant_number":"RGP0034/2018"},{"name":"Biophysically realistic genotype-phenotype maps for regulatory networks","_id":"267C84F4-B435-11E9-9278-68D0E5697425"}],"publication":"bioRxiv","oa":1,"main_file_link":[{"url":"https://doi.org/10.1101/2020.04.08.029405 ","open_access":"1"}],"citation":{"ista":"Grah R, Zoller B, Tkačik G. 2020. Normative models of enhancer function. bioRxiv, 10.1101/2020.04.08.029405.","ieee":"R. Grah, B. Zoller, and G. Tkačik, “Normative models of enhancer function,” bioRxiv. Cold Spring Harbor Laboratory, 2020.","apa":"Grah, R., Zoller, B., & Tkačik, G. (2020). Normative models of enhancer function. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.04.08.029405","ama":"Grah R, Zoller B, Tkačik G. Normative models of enhancer function. bioRxiv. 2020. doi:10.1101/2020.04.08.029405","chicago":"Grah, Rok, Benjamin Zoller, and Gašper Tkačik. “Normative Models of Enhancer Function.” BioRxiv. Cold Spring Harbor Laboratory, 2020. https://doi.org/10.1101/2020.04.08.029405.","mla":"Grah, Rok, et al. “Normative Models of Enhancer Function.” BioRxiv, Cold Spring Harbor Laboratory, 2020, doi:10.1101/2020.04.08.029405.","short":"R. Grah, B. Zoller, G. Tkačik, BioRxiv (2020)."}},{"oa_version":"Published Version","file":[{"access_level":"open_access","file_name":"2020_PlosCompBio_Grah.pdf","file_size":2209325,"content_type":"application/pdf","creator":"dernst","relation":"main_file","file_id":"7579","checksum":"5239dd134dc6e1c71fe7b3ce2953da37","date_updated":"2020-07-14T12:48:00Z","date_created":"2020-03-09T15:12:21Z"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"7569","ddc":["000","570"],"title":"The relation between crosstalk and gene regulation form revisited","status":"public","intvolume":" 16","abstract":[{"lang":"eng","text":"Genes differ in the frequency at which they are expressed and in the form of regulation used to control their activity. In particular, positive or negative regulation can lead to activation of a gene in response to an external signal. Previous works proposed that the form of regulation of a gene correlates with its frequency of usage: positive regulation when the gene is frequently expressed and negative regulation when infrequently expressed. Such network design means that, in the absence of their regulators, the genes are found in their least required activity state, hence regulatory intervention is often necessary. Due to the multitude of genes and regulators, spurious binding and unbinding events, called “crosstalk”, could occur. To determine how the form of regulation affects the global crosstalk in the network, we used a mathematical model that includes multiple regulators and multiple target genes. We found that crosstalk depends non-monotonically on the availability of regulators. Our analysis showed that excess use of regulation entailed by the formerly suggested network design caused high crosstalk levels in a large part of the parameter space. We therefore considered the opposite ‘idle’ design, where the default unregulated state of genes is their frequently required activity state. We found, that ‘idle’ design minimized the use of regulation and thus minimized crosstalk. In addition, we estimated global crosstalk of S. cerevisiae using transcription factors binding data. We demonstrated that even partial network data could suffice to estimate its global crosstalk, suggesting its applicability to additional organisms. We found that S. cerevisiae estimated crosstalk is lower than that of a random network, suggesting that natural selection reduces crosstalk. In summary, our study highlights a new type of protein production cost which is typically overlooked: that of regulatory interference caused by the presence of excess regulators in the cell. It demonstrates the importance of whole-network descriptions, which could show effects missed by single-gene models."}],"issue":"2","type":"journal_article","date_published":"2020-02-25T00:00:00Z","publication":"PLOS Computational Biology","citation":{"ieee":"R. Grah and T. Friedlander, “The relation between crosstalk and gene regulation form revisited,” PLOS Computational Biology, vol. 16, no. 2. Public Library of Science, 2020.","apa":"Grah, R., & Friedlander, T. (2020). The relation between crosstalk and gene regulation form revisited. PLOS Computational Biology. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1007642","ista":"Grah R, Friedlander T. 2020. The relation between crosstalk and gene regulation form revisited. PLOS Computational Biology. 16(2), e1007642.","ama":"Grah R, Friedlander T. The relation between crosstalk and gene regulation form revisited. PLOS Computational Biology. 2020;16(2). doi:10.1371/journal.pcbi.1007642","chicago":"Grah, Rok, and Tamar Friedlander. “The Relation between Crosstalk and Gene Regulation Form Revisited.” PLOS Computational Biology. Public Library of Science, 2020. https://doi.org/10.1371/journal.pcbi.1007642.","short":"R. Grah, T. Friedlander, PLOS Computational Biology 16 (2020).","mla":"Grah, Rok, and Tamar Friedlander. “The Relation between Crosstalk and Gene Regulation Form Revisited.” PLOS Computational Biology, vol. 16, no. 2, e1007642, Public Library of Science, 2020, doi:10.1371/journal.pcbi.1007642."},"article_type":"original","day":"25","article_processing_charge":"No","has_accepted_license":"1","scopus_import":"1","author":[{"id":"483E70DE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2539-3560","first_name":"Rok","last_name":"Grah","full_name":"Grah, Rok"},{"full_name":"Friedlander, Tamar","first_name":"Tamar","last_name":"Friedlander"}],"related_material":{"record":[{"relation":"research_data","status":"deleted","id":"9716"},{"id":"9776","status":"public","relation":"research_data"},{"status":"public","relation":"used_in_publication","id":"9779"},{"id":"8155","status":"public","relation":"dissertation_contains"},{"status":"public","relation":"research_data","id":"9777"}]},"date_updated":"2023-09-12T11:02:24Z","date_created":"2020-03-06T07:39:38Z","volume":16,"year":"2020","publication_status":"published","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publisher":"Public Library of Science","file_date_updated":"2020-07-14T12:48:00Z","article_number":"e1007642","doi":"10.1371/journal.pcbi.1007642","language":[{"iso":"eng"}],"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000526725200019"]},"isi":1,"quality_controlled":"1","month":"02","publication_identifier":{"issn":["1553-7358"]}},{"related_material":{"record":[{"status":"public","relation":"used_in_publication","id":"9283"}]},"contributor":[{"first_name":"Anna A","last_name":"Nagy-Staron","contributor_type":"project_member","id":"3ABC5BA6-F248-11E8-B48F-1D18A9856A87"},{"contributor_type":"project_member","last_name":"Tomasek","first_name":"Kathrin","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Caroline","contributor_type":"project_member","last_name":"Caruso Carter"},{"last_name":"Sonnleitner","contributor_type":"project_member","first_name":"Elisabeth"},{"contributor_type":"project_member","last_name":"Kavcic","first_name":"Bor","orcid":"0000-0001-6041-254X","id":"350F91D2-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Paixão","contributor_type":"project_member","first_name":"Tiago"},{"first_name":"Calin C","contributor_type":"project_manager","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052"}],"author":[{"last_name":"Nagy-Staron","first_name":"Anna A","orcid":"0000-0002-1391-8377","id":"3ABC5BA6-F248-11E8-B48F-1D18A9856A87","full_name":"Nagy-Staron, Anna A"}],"file":[{"checksum":"f57862aeee1690c7effd2b1117d40ed1","success":1,"date_updated":"2020-12-20T09:52:52Z","date_created":"2020-12-20T09:52:52Z","relation":"main_file","file_id":"8952","file_size":523,"content_type":"text/plain","creator":"bkavcic","access_level":"open_access","file_name":"readme.txt"},{"file_name":"GRNs Research depository.gb","access_level":"open_access","content_type":"application/octet-stream","file_size":379228,"creator":"bkavcic","relation":"main_file","file_id":"8954","date_updated":"2020-12-20T22:01:44Z","date_created":"2020-12-20T22:01:44Z","checksum":"f2c6d5232ec6d551b6993991e8689e9f","success":1}],"oa_version":"Published Version","date_updated":"2024-02-21T12:41:57Z","date_created":"2020-12-20T10:00:26Z","year":"2020","_id":"8951","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Institute of Science and Technology Austria","department":[{"_id":"CaGu"}],"status":"public","ddc":["570"],"title":"Sequences of gene regulatory network permutations for the article \"Local genetic context shapes the function of a gene regulatory network\"","file_date_updated":"2020-12-20T22:01:44Z","abstract":[{"text":"Gene expression levels are influenced by multiple coexisting molecular mechanisms. Some of these interactions, such as those of transcription factors and promoters have been studied extensively. However, predicting phenotypes of gene regulatory networks remains a major challenge. Here, we use a well-defined synthetic gene regulatory network to study how network phenotypes depend on local genetic context, i.e. the genetic neighborhood of a transcription factor and its relative position. We show that one gene regulatory network with fixed topology can display not only quantitatively but also qualitatively different phenotypes, depending solely on the local genetic context of its components. Our results demonstrate that changes in local genetic context can place a single transcriptional unit within two separate regulons without the need for complex regulatory sequences. We propose that relative order of individual transcriptional units, with its potential for combinatorial complexity, plays an important role in shaping phenotypes of gene regulatory networks.","lang":"eng"}],"type":"research_data","doi":"10.15479/AT:ISTA:8951","date_published":"2020-12-21T00:00:00Z","oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"citation":{"ista":"Nagy-Staron AA. 2020. Sequences of gene regulatory network permutations for the article ‘Local genetic context shapes the function of a gene regulatory network’, Institute of Science and Technology Austria, 10.15479/AT:ISTA:8951.","ieee":"A. A. Nagy-Staron, “Sequences of gene regulatory network permutations for the article ‘Local genetic context shapes the function of a gene regulatory network.’” Institute of Science and Technology Austria, 2020.","apa":"Nagy-Staron, A. A. (2020). Sequences of gene regulatory network permutations for the article “Local genetic context shapes the function of a gene regulatory network.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8951","ama":"Nagy-Staron AA. Sequences of gene regulatory network permutations for the article “Local genetic context shapes the function of a gene regulatory network.” 2020. doi:10.15479/AT:ISTA:8951","chicago":"Nagy-Staron, Anna A. “Sequences of Gene Regulatory Network Permutations for the Article ‘Local Genetic Context Shapes the Function of a Gene Regulatory Network.’” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8951.","mla":"Nagy-Staron, Anna A. Sequences of Gene Regulatory Network Permutations for the Article “Local Genetic Context Shapes the Function of a Gene Regulatory Network.” Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8951.","short":"A.A. Nagy-Staron, (2020)."},"article_processing_charge":"No","has_accepted_license":"1","month":"12","day":"21","keyword":["Gene regulatory networks","Gene expression","Escherichia coli","Synthetic Biology"]},{"abstract":[{"text":"Organisms cope with change by employing transcriptional regulators. However, when faced with rare environments, the evolution of transcriptional regulators and their promoters may be too slow. We ask whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. By real-time monitoring of gene copy number mutations in E. coli, we show that gene duplications and amplifications enable adaptation to fluctuating environments by rapidly generating copy number, and hence expression level, polymorphism. This ‘amplification-mediated gene expression tuning’ occurs on timescales similar to canonical gene regulation and can deal with rapid environmental changes. Mathematical modeling shows that amplifications also tune gene expression in stochastic environments where transcription factor-based schemes are hard to evolve or maintain. The fleeting nature of gene amplifications gives rise to a generic population-level mechanism that relies on genetic heterogeneity to rapidly tune expression of any gene, without leaving any genomic signature.","lang":"eng"}],"file_date_updated":"2020-07-14T12:47:57Z","type":"research_data","contributor":[{"last_name":"Guet","contributor_type":"project_leader","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"}],"related_material":{"record":[{"id":"7652","relation":"used_in_publication","status":"public"}]},"author":[{"orcid":"0000-0003-2539-3560","id":"483E70DE-F248-11E8-B48F-1D18A9856A87","last_name":"Grah","first_name":"Rok","full_name":"Grah, Rok"}],"oa_version":"Published Version","file":[{"date_updated":"2020-07-14T12:47:57Z","date_created":"2020-01-28T10:39:40Z","checksum":"9d292cf5207b3829225f44c044cdb3fd","file_id":"7384","relation":"main_file","creator":"rgrah","file_size":73363365,"content_type":"application/zip","file_name":"Scripts.zip","access_level":"open_access"},{"date_updated":"2020-07-14T12:47:57Z","date_created":"2020-01-28T10:39:30Z","checksum":"4076ceab32ef588cc233802bab24c1ab","file_id":"7385","relation":"main_file","creator":"rgrah","file_size":962,"content_type":"text/plain","file_name":"READ_ME_MAIN.txt","access_level":"open_access"}],"date_created":"2020-01-28T10:41:49Z","date_updated":"2024-02-21T12:42:31Z","_id":"7383","year":"2020","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publisher":"Institute of Science and Technology Austria","status":"public","title":"Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation","has_accepted_license":"1","article_processing_charge":"No","day":"28","month":"01","keyword":["Matlab scripts","analysis of microfluidics","mathematical model"],"date_published":"2020-01-28T00:00:00Z","doi":"10.15479/AT:ISTA:7383","citation":{"chicago":"Grah, Rok. “Matlab Scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression Regulation.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:7383.","short":"R. Grah, (2020).","mla":"Grah, Rok. Matlab Scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression Regulation. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:7383.","ieee":"R. Grah, “Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation.” Institute of Science and Technology Austria, 2020.","apa":"Grah, R. (2020). Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7383","ista":"Grah R. 2020. Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation, Institute of Science and Technology Austria, 10.15479/AT:ISTA:7383.","ama":"Grah R. Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation. 2020. doi:10.15479/AT:ISTA:7383"},"oa":1},{"file_date_updated":"2021-10-31T23:30:05Z","publication_status":"published","publisher":"Institute of Science and Technology Austria","department":[{"_id":"CaGu"}],"year":"2020","date_created":"2020-04-24T16:00:51Z","date_updated":"2023-09-22T09:20:10Z","author":[{"full_name":"Kainrath, Stephanie","id":"32CFBA64-F248-11E8-B48F-1D18A9856A87","first_name":"Stephanie","last_name":"Kainrath"}],"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"1028"}]},"month":"04","publication_identifier":{"eissn":["2663-337X"]},"oa":1,"supervisor":[{"first_name":"Harald L","last_name":"Janovjak","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8023-9315","full_name":"Janovjak, Harald L"}],"degree_awarded":"PhD","language":[{"iso":"eng"}],"doi":"10.15479/AT:ISTA:7680","alternative_title":["ISTA Thesis"],"type":"dissertation","abstract":[{"lang":"eng","text":"Proteins and their complex dynamic interactions regulate cellular mechanisms from sensing and transducing extracellular signals, to mediating genetic responses, and sustaining or changing cell morphology. To manipulate these protein-protein interactions (PPIs) that govern the behavior and fate of cells, synthetically constructed, genetically encoded tools provide the means to precisely target proteins of interest (POIs), and control their subcellular localization and activity in vitro and in vivo. Ideal synthetic tools react to an orthogonal cue, i.e. a trigger that does not activate any other endogenous process, thereby allowing manipulation of the POI alone.\r\nIn optogenetics, naturally occurring photosensory domain from plants, algae and bacteria are re-purposed and genetically fused to POIs. Illumination with light of a specific wavelength triggers a conformational change that can mediate PPIs, such as dimerization or oligomerization. By using light as a trigger, these tools can be activated with high spatial and temporal precision, on subcellular and millisecond scales. Chemogenetic tools consist of protein domains that recognize and bind small molecules. By genetic fusion to POIs, these domains can mediate PPIs upon addition of their specific ligands, which are often synthetically designed to provide highly specific interactions and exhibit good bioavailability.\r\nMost optogenetic tools to mediate PPIs are based on well-studied photoreceptors responding to red, blue or near-UV light, leaving a striking gap in the green band of the visible light spectrum. Among both optogenetic and chemogenetic tools, there is an abundance of methods to induce PPIs, but tools to disrupt them require UV illumination, rely on covalent linkage and subsequent enzymatic cleavage or initially result in protein clustering of unknown stoichiometry.\r\nThis work describes how the recently structurally and photochemically characterized green-light responsive cobalamin-binding domains (CBDs) from bacterial transcription factors were re-purposed to function as a green-light responsive optogenetic tool. In contrast to previously engineered optogenetic tools, CBDs do not induce PPI, but rather confer a PPI already upon expression, which can be rapidly disrupted by illumination. This was employed to mimic inhibition of constitutive activity of a growth factor receptor, and successfully implement for cell signalling in mammalian cells and in vivo to rescue development in zebrafish. This work further describes the development and application of a chemically induced de-dimerizer (CDD) based on a recently identified and structurally described bacterial oxyreductase. CDD forms a dimer upon expression in absence of its cofactor, the flavin derivative F420. Safety and of domain expression and ligand exposure are demonstrated in vitro and in vivo in zebrafish. The system is further applied to inhibit cell signalling output from a chimeric receptor upon F420 treatment.\r\nCBDs and CDD expand the repertoire of synthetic tools by providing novel mechanisms of mediating PPIs, and by recognizing previously not utilized cues. In the future, they can readily be combined with existing synthetic tools to functionally manipulate PPIs in vitro and in vivo."}],"status":"public","title":"Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals","ddc":["570"],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"7680","oa_version":"None","file":[{"file_name":"Thesis_without-signatures_PDFA.pdf","access_level":"open_access","content_type":"application/pdf","file_size":3268017,"creator":"stgingl","relation":"main_file","embargo":"2021-10-30","file_id":"7692","date_updated":"2021-10-31T23:30:05Z","date_created":"2020-04-28T11:19:21Z","checksum":"fb9a4468eb27be92690728e35c823796"},{"file_name":"Thesis_without signatures.docx","embargo_to":"open_access","access_level":"closed","creator":"stgingl","file_size":5167703,"content_type":"application/octet-stream","file_id":"7693","relation":"source_file","date_updated":"2021-10-31T23:30:05Z","date_created":"2020-04-28T11:19:24Z","checksum":"f6c80ca97104a631a328cb79a2c53493"}],"day":"24","article_processing_charge":"No","has_accepted_license":"1","page":"98","citation":{"short":"S. Kainrath, Synthetic Tools for Optogenetic and Chemogenetic Inhibition of Cellular Signals, Institute of Science and Technology Austria, 2020.","mla":"Kainrath, Stephanie. Synthetic Tools for Optogenetic and Chemogenetic Inhibition of Cellular Signals. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:7680.","chicago":"Kainrath, Stephanie. “Synthetic Tools for Optogenetic and Chemogenetic Inhibition of Cellular Signals.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:7680.","ama":"Kainrath S. Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals. 2020. doi:10.15479/AT:ISTA:7680","ieee":"S. Kainrath, “Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals,” Institute of Science and Technology Austria, 2020.","apa":"Kainrath, S. (2020). Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7680","ista":"Kainrath S. 2020. Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals. Institute of Science and Technology Austria."},"date_published":"2020-04-24T00:00:00Z"},{"scopus_import":"1","day":"01","has_accepted_license":"1","article_processing_charge":"No","publication":"Nature Ecology & Evolution","citation":{"short":"I. Tomanek, R. Grah, M. Lagator, A.M.C. Andersson, J.P. Bollback, G. Tkačik, C.C. Guet, Nature Ecology & Evolution 4 (2020) 612–625.","mla":"Tomanek, Isabella, et al. “Gene Amplification as a Form of Population-Level Gene Expression Regulation.” Nature Ecology & Evolution, vol. 4, no. 4, Springer Nature, 2020, pp. 612–25, doi:10.1038/s41559-020-1132-7.","chicago":"Tomanek, Isabella, Rok Grah, M. Lagator, A. M. C. Andersson, Jonathan P Bollback, Gašper Tkačik, and Calin C Guet. “Gene Amplification as a Form of Population-Level Gene Expression Regulation.” Nature Ecology & Evolution. Springer Nature, 2020. https://doi.org/10.1038/s41559-020-1132-7.","ama":"Tomanek I, Grah R, Lagator M, et al. Gene amplification as a form of population-level gene expression regulation. Nature Ecology & Evolution. 2020;4(4):612-625. doi:10.1038/s41559-020-1132-7","apa":"Tomanek, I., Grah, R., Lagator, M., Andersson, A. M. C., Bollback, J. P., Tkačik, G., & Guet, C. C. (2020). Gene amplification as a form of population-level gene expression regulation. Nature Ecology & Evolution. Springer Nature. https://doi.org/10.1038/s41559-020-1132-7","ieee":"I. Tomanek et al., “Gene amplification as a form of population-level gene expression regulation,” Nature Ecology & Evolution, vol. 4, no. 4. Springer Nature, pp. 612–625, 2020.","ista":"Tomanek I, Grah R, Lagator M, Andersson AMC, Bollback JP, Tkačik G, Guet CC. 2020. Gene amplification as a form of population-level gene expression regulation. Nature Ecology & Evolution. 4(4), 612–625."},"article_type":"original","page":"612-625","date_published":"2020-04-01T00:00:00Z","type":"journal_article","abstract":[{"text":"Organisms cope with change by taking advantage of transcriptional regulators. However, when faced with rare environments, the evolution of transcriptional regulators and their promoters may be too slow. Here, we investigate whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. Using real-time monitoring of gene-copy-number mutations in Escherichia coli, we show that gene duplications and amplifications enable adaptation to fluctuating environments by rapidly generating copy-number and, therefore, expression-level polymorphisms. This amplification-mediated gene expression tuning (AMGET) occurs on timescales that are similar to canonical gene regulation and can respond to rapid environmental changes. Mathematical modelling shows that amplifications also tune gene expression in stochastic environments in which transcription-factor-based schemes are hard to evolve or maintain. The fleeting nature of gene amplifications gives rise to a generic population-level mechanism that relies on genetic heterogeneity to rapidly tune the expression of any gene, without leaving any genomic signature.","lang":"eng"}],"issue":"4","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"7652","ddc":["570"],"title":"Gene amplification as a form of population-level gene expression regulation","status":"public","intvolume":" 4","file":[{"date_updated":"2020-10-09T09:56:01Z","date_created":"2020-10-09T09:56:01Z","checksum":"ef3bbf42023e30b2c24a6278025d2040","success":1,"relation":"main_file","file_id":"8640","file_size":745242,"content_type":"application/pdf","creator":"dernst","file_name":"2020_NatureEcolEvo_Tomanek.pdf","access_level":"open_access"}],"oa_version":"Submitted Version","month":"04","publication_identifier":{"issn":["2397-334X"]},"oa":1,"external_id":{"isi":["000519008300005"]},"isi":1,"quality_controlled":"1","project":[{"_id":"267C84F4-B435-11E9-9278-68D0E5697425","name":"Biophysically realistic genotype-phenotype maps for regulatory networks"}],"doi":"10.1038/s41559-020-1132-7","language":[{"iso":"eng"}],"file_date_updated":"2020-10-09T09:56:01Z","acknowledgement":"We thank L. Hurst, N. Barton, M. Pleska, M. Steinrück, B. Kavcic and A. Staron for input on the manuscript, and To. Bergmiller and R. Chait for help with microfluidics experiments. I.T. is a recipient the OMV fellowship. R.G. is a recipient of a DOC (Doctoral Fellowship Programme of the Austrian Academy of Sciences) Fellowship of the Austrian Academy of Sciences.","year":"2020","publication_status":"published","publisher":"Springer Nature","department":[{"_id":"GaTk"},{"_id":"CaGu"}],"author":[{"first_name":"Isabella","last_name":"Tomanek","id":"3981F020-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6197-363X","full_name":"Tomanek, Isabella"},{"id":"483E70DE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2539-3560","first_name":"Rok","last_name":"Grah","full_name":"Grah, Rok"},{"full_name":"Lagator, M.","last_name":"Lagator","first_name":"M."},{"first_name":"A. M. C.","last_name":"Andersson","full_name":"Andersson, A. M. C."},{"last_name":"Bollback","first_name":"Jonathan P","orcid":"0000-0002-4624-4612","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","full_name":"Bollback, Jonathan P"},{"full_name":"Tkačik, Gašper","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","last_name":"Tkačik","first_name":"Gašper"},{"first_name":"Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C"}],"related_material":{"record":[{"id":"8155","status":"public","relation":"dissertation_contains"},{"id":"7383","status":"public","relation":"research_data"},{"status":"public","relation":"research_data","id":"7016"},{"relation":"used_in_publication","status":"public","id":"8653"}],"link":[{"description":"News on IST Homepage","relation":"press_release","url":"https://ist.ac.at/en/news/how-to-thrive-without-gene-regulation/"}]},"date_created":"2020-04-08T15:20:53Z","date_updated":"2024-03-28T23:30:37Z","volume":4},{"file_date_updated":"2021-10-20T22:30:03Z","date_created":"2020-10-13T13:02:33Z","date_updated":"2023-09-07T13:22:42Z","author":[{"full_name":"Tomanek, Isabella","id":"3981F020-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6197-363X","first_name":"Isabella","last_name":"Tomanek"}],"related_material":{"record":[{"relation":"research_data","status":"public","id":"7652"}]},"publication_status":"published","department":[{"_id":"CaGu"}],"publisher":"Institute of Science and Technology Austria","year":"2020","month":"10","publication_identifier":{"issn":["2663-337X"]},"degree_awarded":"PhD","supervisor":[{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet","full_name":"Guet, Calin C"}],"language":[{"iso":"eng"}],"doi":"10.15479/AT:ISTA:8653","oa":1,"abstract":[{"lang":"eng","text":"Mutations are the raw material of evolution and come in many different flavors. Point mutations change a single letter in the DNA sequence, while copy number mutations like duplications or deletions add or remove many letters of the DNA sequence simultaneously. Each type of mutation exhibits specific properties like its rate of formation and reversal. \r\nGene expression is a fundamental phenotype that can be altered by both, point and copy number mutations. The following thesis is concerned with the dynamics of gene expression evolution and how it is affected by the properties exhibited by point and copy number mutations. Specifically, we are considering i) copy number mutations during adaptation to fluctuating environments and ii) the interaction of copy number and point mutations during adaptation to constant environments. "}],"alternative_title":["ISTA Thesis"],"type":"dissertation","file":[{"creator":"itomanek","file_size":25131884,"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","access_level":"closed","file_name":"Thesis_ITomanek_final_201016.docx","embargo_to":"open_access","checksum":"c01d9f59794b4b70528f37637c17ad02","date_created":"2020-10-16T12:14:21Z","date_updated":"2021-10-20T22:30:03Z","file_id":"8666","relation":"source_file"},{"relation":"main_file","embargo":"2021-10-19","file_id":"8667","date_updated":"2021-10-20T22:30:03Z","date_created":"2020-10-16T12:14:21Z","checksum":"f8edbc3b0f81a780e13ca1e561d42d8b","file_name":"Thesis_ITomanek_final_201016.pdf","access_level":"open_access","file_size":15405675,"content_type":"application/pdf","creator":"itomanek"}],"oa_version":"Published Version","status":"public","ddc":["576"],"title":"The evolution of gene expression by copy number and point mutations","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"8653","day":"13","article_processing_charge":"No","has_accepted_license":"1","keyword":["duplication","amplification","promoter","CNV","AMGET","experimental evolution","Escherichia coli"],"date_published":"2020-10-13T00:00:00Z","page":"117","citation":{"ama":"Tomanek I. The evolution of gene expression by copy number and point mutations. 2020. doi:10.15479/AT:ISTA:8653","ieee":"I. Tomanek, “The evolution of gene expression by copy number and point mutations,” Institute of Science and Technology Austria, 2020.","apa":"Tomanek, I. (2020). The evolution of gene expression by copy number and point mutations. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8653","ista":"Tomanek I. 2020. The evolution of gene expression by copy number and point mutations. Institute of Science and Technology Austria.","short":"I. Tomanek, The Evolution of Gene Expression by Copy Number and Point Mutations, Institute of Science and Technology Austria, 2020.","mla":"Tomanek, Isabella. The Evolution of Gene Expression by Copy Number and Point Mutations. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8653.","chicago":"Tomanek, Isabella. “The Evolution of Gene Expression by Copy Number and Point Mutations.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8653."}},{"date_published":"2019-05-01T00:00:00Z","publication":"Nature Communications","citation":{"chicago":"Chassin, Hélène, Marius Müller, Marcel Tigges, Leo Scheller, Moritz Lang, and Martin Fussenegger. “A Modular Degron Library for Synthetic Circuits in Mammalian Cells.” Nature Communications. Springer Nature, 2019. https://doi.org/10.1038/s41467-019-09974-5.","mla":"Chassin, Hélène, et al. “A Modular Degron Library for Synthetic Circuits in Mammalian Cells.” Nature Communications, vol. 10, no. 1, 2013, Springer Nature, 2019, doi:10.1038/s41467-019-09974-5.","short":"H. Chassin, M. Müller, M. Tigges, L. Scheller, M. Lang, M. Fussenegger, Nature Communications 10 (2019).","ista":"Chassin H, Müller M, Tigges M, Scheller L, Lang M, Fussenegger M. 2019. A modular degron library for synthetic circuits in mammalian cells. Nature Communications. 10(1), 2013.","ieee":"H. Chassin, M. Müller, M. Tigges, L. Scheller, M. Lang, and M. Fussenegger, “A modular degron library for synthetic circuits in mammalian cells,” Nature Communications, vol. 10, no. 1. Springer Nature, 2019.","apa":"Chassin, H., Müller, M., Tigges, M., Scheller, L., Lang, M., & Fussenegger, M. (2019). A modular degron library for synthetic circuits in mammalian cells. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-019-09974-5","ama":"Chassin H, Müller M, Tigges M, Scheller L, Lang M, Fussenegger M. A modular degron library for synthetic circuits in mammalian cells. Nature Communications. 2019;10(1). doi:10.1038/s41467-019-09974-5"},"day":"01","article_processing_charge":"No","has_accepted_license":"1","scopus_import":"1","oa_version":"Published Version","file":[{"access_level":"open_access","file_name":"2019_NatureComm_Chassin.pdf","creator":"dernst","file_size":1191827,"content_type":"application/pdf","file_id":"6471","relation":"main_file","checksum":"e214d3e4f8c81e35981583c4569b51b8","date_updated":"2020-07-14T12:47:31Z","date_created":"2019-05-20T07:33:54Z"}],"_id":"6465","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","ddc":["570"],"title":"A modular degron library for synthetic circuits in mammalian cells","status":"public","intvolume":" 10","abstract":[{"lang":"eng","text":"Tight control over protein degradation is a fundamental requirement for cells to respond rapidly to various stimuli and adapt to a fluctuating environment. Here we develop a versatile, easy-to-handle library of destabilizing tags (degrons) for the precise regulation of protein expression profiles in mammalian cells by modulating target protein half-lives in a predictable manner. Using the well-established tetracycline gene-regulation system as a model, we show that the dynamics of protein expression can be tuned by fusing appropriate degron tags to gene regulators. Next, we apply this degron library to tune a synthetic pulse-generating circuit in mammalian cells. With this toolbox we establish a set of pulse generators with tailored pulse lengths and magnitudes of protein expression. This methodology will prove useful in the functional roles of essential proteins, fine-tuning of gene-expression systems, and enabling a higher complexity in the design of synthetic biological systems in mammalian cells."}],"issue":"1","type":"journal_article","doi":"10.1038/s41467-019-09974-5","language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000466338600006"]},"oa":1,"isi":1,"quality_controlled":"1","month":"05","publication_identifier":{"eissn":["20411723"]},"author":[{"full_name":"Chassin, Hélène","first_name":"Hélène","last_name":"Chassin"},{"full_name":"Müller, Marius","first_name":"Marius","last_name":"Müller"},{"full_name":"Tigges, Marcel","first_name":"Marcel","last_name":"Tigges"},{"full_name":"Scheller, Leo","last_name":"Scheller","first_name":"Leo"},{"full_name":"Lang, Moritz","first_name":"Moritz","last_name":"Lang","id":"29E0800A-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Fussenegger, Martin","first_name":"Martin","last_name":"Fussenegger"}],"related_material":{"link":[{"url":"https://doi.org/10.1038/s41467-023-36111-0","relation":"erratum"}]},"date_updated":"2023-08-25T10:33:51Z","date_created":"2019-05-19T21:59:14Z","volume":10,"year":"2019","publication_status":"published","publisher":"Springer Nature","department":[{"_id":"CaGu"}],"file_date_updated":"2020-07-14T12:47:31Z","article_number":"2013"},{"citation":{"short":"C. Igler, S.T. Abedon, Frontiers in Microbiology 10 (2019).","mla":"Igler, Claudia, and Stephen T. Abedon. “Commentary: A Host-Produced Quorum-Sensing Autoinducer Controls a Phage Lysis-Lysogeny Decision.” Frontiers in Microbiology, vol. 10, 1171, Frontiers, 2019, doi:10.3389/fmicb.2019.01171.","chicago":"Igler, Claudia, and Stephen T. Abedon. “Commentary: A Host-Produced Quorum-Sensing Autoinducer Controls a Phage Lysis-Lysogeny Decision.” Frontiers in Microbiology. Frontiers, 2019. https://doi.org/10.3389/fmicb.2019.01171.","ama":"Igler C, Abedon ST. Commentary: A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision. Frontiers in Microbiology. 2019;10. doi:10.3389/fmicb.2019.01171","apa":"Igler, C., & Abedon, S. T. (2019). Commentary: A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision. Frontiers in Microbiology. Frontiers. https://doi.org/10.3389/fmicb.2019.01171","ieee":"C. Igler and S. T. Abedon, “Commentary: A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision,” Frontiers in Microbiology, vol. 10. Frontiers, 2019.","ista":"Igler C, Abedon ST. 2019. Commentary: A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision. Frontiers in Microbiology. 10, 1171."},"publication":"Frontiers in Microbiology","date_published":"2019-06-03T00:00:00Z","scopus_import":"1","article_processing_charge":"Yes (via OA deal)","has_accepted_license":"1","day":"03","intvolume":" 10","title":"Commentary: A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision","ddc":["570"],"status":"public","_id":"6717","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file":[{"date_updated":"2020-07-14T12:47:38Z","date_created":"2019-07-29T07:51:54Z","checksum":"317a06067e9a8e717bb55f23e0d77ba7","relation":"main_file","file_id":"6722","content_type":"application/pdf","file_size":246151,"creator":"apreinsp","file_name":"2019_Frontiers_Igler.pdf","access_level":"open_access"}],"oa_version":"Published Version","type":"journal_article","abstract":[{"text":"With the recent publication by Silpe and Bassler (2019), considering phage detection of a bacterial quorum-sensing (QS) autoinducer, we now have as many as five examples of phage-associated intercellular communication (Table 1). Each potentially involves ecological inferences by phages as to concentrations of surrounding phage-infected or uninfected bacteria. While the utility of phage detection of bacterial QS molecules may at first glance appear to be straightforward, we suggest in this commentary that the underlying ecological explanation is unlikely to be simple.","lang":"eng"}],"project":[{"grant_number":"24573","_id":"251EE76E-B435-11E9-9278-68D0E5697425","name":"Design principles underlying genetic switch architecture (DOC Fellowship)"}],"quality_controlled":"1","isi":1,"external_id":{"isi":["000470131200001"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"language":[{"iso":"eng"}],"doi":"10.3389/fmicb.2019.01171","month":"06","publisher":"Frontiers","department":[{"_id":"CaGu"}],"publication_status":"published","year":"2019","volume":10,"date_created":"2019-07-28T21:59:18Z","date_updated":"2023-08-29T06:41:20Z","author":[{"full_name":"Igler, Claudia","id":"46613666-F248-11E8-B48F-1D18A9856A87","last_name":"Igler","first_name":"Claudia"},{"last_name":"Abedon","first_name":"Stephen T.","full_name":"Abedon, Stephen T."}],"article_number":"1171","file_date_updated":"2020-07-14T12:47:38Z"},{"year":"2019","publisher":"Public Library of Science","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publication_status":"published","related_material":{"record":[{"status":"public","relation":"research_data","id":"9786"}]},"author":[{"last_name":"Ruess","first_name":"Jakob","orcid":"0000-0003-1615-3282","id":"4A245D00-F248-11E8-B48F-1D18A9856A87","full_name":"Ruess, Jakob"},{"orcid":"0000-0001-7460-7479","id":"4569785E-F248-11E8-B48F-1D18A9856A87","last_name":"Pleska","first_name":"Maros","full_name":"Pleska, Maros"},{"full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C"},{"full_name":"Tkačik, Gašper","first_name":"Gašper","last_name":"Tkačik","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455"}],"volume":15,"date_created":"2019-08-11T21:59:19Z","date_updated":"2023-08-29T07:10:06Z","article_number":"e1007168","file_date_updated":"2020-07-14T12:47:40Z","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000481577700032"]},"oa":1,"project":[{"_id":"251D65D8-B435-11E9-9278-68D0E5697425","grant_number":"24210","name":"Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level"},{"grant_number":"RGY0079/2011","_id":"251BCBEC-B435-11E9-9278-68D0E5697425","name":"Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification Systems"}],"isi":1,"quality_controlled":"1","doi":"10.1371/journal.pcbi.1007168","language":[{"iso":"eng"}],"publication_identifier":{"eissn":["1553-7358"]},"month":"07","_id":"6784","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","intvolume":" 15","status":"public","ddc":["570"],"title":"Molecular noise of innate immunity shapes bacteria-phage ecologies","file":[{"relation":"main_file","file_id":"6803","date_created":"2019-08-12T12:27:26Z","date_updated":"2020-07-14T12:47:40Z","checksum":"7ded4721b41c2a0fc66a1c634540416a","file_name":"2019_PlosComputBiology_Ruess.pdf","access_level":"open_access","file_size":2200003,"content_type":"application/pdf","creator":"dernst"}],"oa_version":"Published Version","type":"journal_article","issue":"7","abstract":[{"text":"Mathematical models have been used successfully at diverse scales of biological organization, ranging from ecology and population dynamics to stochastic reaction events occurring between individual molecules in single cells. Generally, many biological processes unfold across multiple scales, with mutations being the best studied example of how stochasticity at the molecular scale can influence outcomes at the population scale. In many other contexts, however, an analogous link between micro- and macro-scale remains elusive, primarily due to the challenges involved in setting up and analyzing multi-scale models. Here, we employ such a model to investigate how stochasticity propagates from individual biochemical reaction events in the bacterial innate immune system to the ecology of bacteria and bacterial viruses. We show analytically how the dynamics of bacterial populations are shaped by the activities of immunity-conferring enzymes in single cells and how the ecological consequences imply optimal bacterial defense strategies against viruses. Our results suggest that bacterial populations in the presence of viruses can either optimize their initial growth rate or their population size, with the first strategy favoring simple immunity featuring a single restriction modification system and the second strategy favoring complex bacterial innate immunity featuring several simultaneously active restriction modification systems.","lang":"eng"}],"citation":{"short":"J. Ruess, M. Pleska, C.C. Guet, G. Tkačik, PLoS Computational Biology 15 (2019).","mla":"Ruess, Jakob, et al. “Molecular Noise of Innate Immunity Shapes Bacteria-Phage Ecologies.” PLoS Computational Biology, vol. 15, no. 7, e1007168, Public Library of Science, 2019, doi:10.1371/journal.pcbi.1007168.","chicago":"Ruess, Jakob, Maros Pleska, Calin C Guet, and Gašper Tkačik. “Molecular Noise of Innate Immunity Shapes Bacteria-Phage Ecologies.” PLoS Computational Biology. Public Library of Science, 2019. https://doi.org/10.1371/journal.pcbi.1007168.","ama":"Ruess J, Pleska M, Guet CC, Tkačik G. Molecular noise of innate immunity shapes bacteria-phage ecologies. PLoS Computational Biology. 2019;15(7). doi:10.1371/journal.pcbi.1007168","apa":"Ruess, J., Pleska, M., Guet, C. C., & Tkačik, G. (2019). Molecular noise of innate immunity shapes bacteria-phage ecologies. PLoS Computational Biology. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1007168","ieee":"J. Ruess, M. Pleska, C. C. Guet, and G. Tkačik, “Molecular noise of innate immunity shapes bacteria-phage ecologies,” PLoS Computational Biology, vol. 15, no. 7. Public Library of Science, 2019.","ista":"Ruess J, Pleska M, Guet CC, Tkačik G. 2019. Molecular noise of innate immunity shapes bacteria-phage ecologies. PLoS Computational Biology. 15(7), e1007168."},"publication":"PLoS Computational Biology","article_type":"original","date_published":"2019-07-02T00:00:00Z","scopus_import":"1","has_accepted_license":"1","article_processing_charge":"No","day":"02"},{"citation":{"ama":"Ruess J, Pleska M, Guet CC, Tkačik G. Supporting text and results. 2019. doi:10.1371/journal.pcbi.1007168.s001","ista":"Ruess J, Pleska M, Guet CC, Tkačik G. 2019. Supporting text and results, Public Library of Science, 10.1371/journal.pcbi.1007168.s001.","apa":"Ruess, J., Pleska, M., Guet, C. C., & Tkačik, G. (2019). Supporting text and results. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1007168.s001","ieee":"J. Ruess, M. Pleska, C. C. Guet, and G. Tkačik, “Supporting text and results.” Public Library of Science, 2019.","mla":"Ruess, Jakob, et al. Supporting Text and Results. Public Library of Science, 2019, doi:10.1371/journal.pcbi.1007168.s001.","short":"J. Ruess, M. Pleska, C.C. Guet, G. Tkačik, (2019).","chicago":"Ruess, Jakob, Maros Pleska, Calin C Guet, and Gašper Tkačik. “Supporting Text and Results.” Public Library of Science, 2019. https://doi.org/10.1371/journal.pcbi.1007168.s001."},"doi":"10.1371/journal.pcbi.1007168.s001","date_published":"2019-07-02T00:00:00Z","month":"07","day":"02","article_processing_charge":"No","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","_id":"9786","year":"2019","status":"public","title":"Supporting text and results","publisher":"Public Library of Science","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"author":[{"full_name":"Ruess, Jakob","first_name":"Jakob","last_name":"Ruess","id":"4A245D00-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1615-3282"},{"first_name":"Maros","last_name":"Pleska","id":"4569785E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7460-7479","full_name":"Pleska, Maros"},{"full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet"},{"full_name":"Tkačik, Gašper","first_name":"Gašper","last_name":"Tkačik","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455"}],"related_material":{"record":[{"id":"6784","relation":"used_in_publication","status":"public"}]},"date_updated":"2023-08-29T07:10:05Z","date_created":"2021-08-06T08:23:43Z","oa_version":"Published Version","type":"research_data_reference"},{"publication_identifier":{"issn":["0302-9743"],"isbn":["9783030313036","9783030313043"],"eissn":["1611-3349"]},"month":"09","language":[{"iso":"eng"}],"doi":"10.1007/978-3-030-31304-3_9","conference":{"start_date":"2019-09-18","location":"Trieste, Italy","end_date":"2019-09-20","name":"CMSB: Computational Methods in Systems Biology"},"project":[{"call_identifier":"FWF","name":"The Wittgenstein Prize","_id":"25F42A32-B435-11E9-9278-68D0E5697425","grant_number":"Z211"},{"name":"Design principles underlying genetic switch architecture","grant_number":"24573","_id":"251EE76E-B435-11E9-9278-68D0E5697425"}],"isi":1,"quality_controlled":"1","external_id":{"isi":["000557875100009"]},"volume":11773,"date_created":"2019-12-04T16:07:50Z","date_updated":"2023-09-06T11:18:08Z","author":[{"full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet"},{"orcid":"0000−0002−2985−7724","id":"40876CD8-F248-11E8-B48F-1D18A9856A87","last_name":"Henzinger","first_name":"Thomas A","full_name":"Henzinger, Thomas A"},{"full_name":"Igler, Claudia","first_name":"Claudia","last_name":"Igler","id":"46613666-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Petrov, Tatjana","first_name":"Tatjana","last_name":"Petrov","id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9041-0905"},{"first_name":"Ali","last_name":"Sezgin","id":"4C7638DA-F248-11E8-B48F-1D18A9856A87","full_name":"Sezgin, Ali"}],"publisher":"Springer Nature","department":[{"_id":"CaGu"},{"_id":"ToHe"}],"publication_status":"published","year":"2019","article_processing_charge":"No","day":"17","scopus_import":"1","date_published":"2019-09-17T00:00:00Z","page":"155-187","citation":{"ista":"Guet CC, Henzinger TA, Igler C, Petrov T, Sezgin A. 2019. Transient memory in gene regulation. 17th International Conference on Computational Methods in Systems Biology. CMSB: Computational Methods in Systems Biology, LNCS, vol. 11773, 155–187.","ieee":"C. C. Guet, T. A. Henzinger, C. Igler, T. Petrov, and A. Sezgin, “Transient memory in gene regulation,” in 17th International Conference on Computational Methods in Systems Biology, Trieste, Italy, 2019, vol. 11773, pp. 155–187.","apa":"Guet, C. C., Henzinger, T. A., Igler, C., Petrov, T., & Sezgin, A. (2019). Transient memory in gene regulation. In 17th International Conference on Computational Methods in Systems Biology (Vol. 11773, pp. 155–187). Trieste, Italy: Springer Nature. https://doi.org/10.1007/978-3-030-31304-3_9","ama":"Guet CC, Henzinger TA, Igler C, Petrov T, Sezgin A. Transient memory in gene regulation. In: 17th International Conference on Computational Methods in Systems Biology. Vol 11773. Springer Nature; 2019:155-187. doi:10.1007/978-3-030-31304-3_9","chicago":"Guet, Calin C, Thomas A Henzinger, Claudia Igler, Tatjana Petrov, and Ali Sezgin. “Transient Memory in Gene Regulation.” In 17th International Conference on Computational Methods in Systems Biology, 11773:155–87. Springer Nature, 2019. https://doi.org/10.1007/978-3-030-31304-3_9.","mla":"Guet, Calin C., et al. “Transient Memory in Gene Regulation.” 17th International Conference on Computational Methods in Systems Biology, vol. 11773, Springer Nature, 2019, pp. 155–87, doi:10.1007/978-3-030-31304-3_9.","short":"C.C. Guet, T.A. Henzinger, C. Igler, T. Petrov, A. Sezgin, in:, 17th International Conference on Computational Methods in Systems Biology, Springer Nature, 2019, pp. 155–187."},"publication":"17th International Conference on Computational Methods in Systems Biology","abstract":[{"lang":"eng","text":"The expression of a gene is characterised by its transcription factors and the function processing them. If the transcription factors are not affected by gene products, the regulating function is often represented as a combinational logic circuit, where the outputs (product) are determined by current input values (transcription factors) only, and are hence independent on their relative arrival times. However, the simultaneous arrival of transcription factors (TFs) in genetic circuits is a strong assumption, given that the processes of transcription and translation of a gene into a protein introduce intrinsic time delays and that there is no global synchronisation among the arrival times of different molecular species at molecular targets.\r\n\r\nIn this paper, we construct an experimentally implementable genetic circuit with two inputs and a single output, such that, in presence of small delays in input arrival, the circuit exhibits qualitatively distinct observable phenotypes. In particular, these phenotypes are long lived transients: they all converge to a single value, but so slowly, that they seem stable for an extended time period, longer than typical experiment duration. We used rule-based language to prototype our circuit, and we implemented a search for finding the parameter combinations raising the phenotypes of interest.\r\n\r\nThe behaviour of our prototype circuit has wide implications. First, it suggests that GRNs can exploit event timing to create phenotypes. Second, it opens the possibility that GRNs are using event timing to react to stimuli and memorise events, without explicit feedback in regulation. From the modelling perspective, our prototype circuit demonstrates the critical importance of analysing the transient dynamics at the promoter binding sites of the DNA, before applying rapid equilibrium assumptions."}],"alternative_title":["LNCS"],"type":"conference","oa_version":"None","intvolume":" 11773","title":"Transient memory in gene regulation","status":"public","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"7147"},{"month":"02","doi":"10.1007/s00294-018-0879-8","language":[{"iso":"eng"}],"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000456958800017"]},"quality_controlled":"1","isi":1,"project":[{"call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme","grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425"}],"file_date_updated":"2020-07-14T12:44:47Z","publist_id":"7785","ec_funded":1,"author":[{"full_name":"Nikolic, Nela","last_name":"Nikolic","first_name":"Nela","orcid":"0000-0001-9068-6090","id":"42D9CABC-F248-11E8-B48F-1D18A9856A87"}],"date_created":"2018-12-11T11:44:50Z","date_updated":"2023-09-08T13:23:42Z","volume":65,"year":"2019","publication_status":"published","department":[{"_id":"CaGu"}],"publisher":"Springer","day":"01","article_processing_charge":"Yes (via OA deal)","has_accepted_license":"1","scopus_import":"1","date_published":"2019-02-01T00:00:00Z","publication":"Current Genetics","citation":{"ista":"Nikolic N. 2019. Autoregulation of bacterial gene expression: lessons from the MazEF toxin–antitoxin system. Current Genetics. 65(1), 133–138.","apa":"Nikolic, N. (2019). Autoregulation of bacterial gene expression: lessons from the MazEF toxin–antitoxin system. Current Genetics. Springer. https://doi.org/10.1007/s00294-018-0879-8","ieee":"N. Nikolic, “Autoregulation of bacterial gene expression: lessons from the MazEF toxin–antitoxin system,” Current Genetics, vol. 65, no. 1. Springer, pp. 133–138, 2019.","ama":"Nikolic N. Autoregulation of bacterial gene expression: lessons from the MazEF toxin–antitoxin system. Current Genetics. 2019;65(1):133-138. doi:10.1007/s00294-018-0879-8","chicago":"Nikolic, Nela. “Autoregulation of Bacterial Gene Expression: Lessons from the MazEF Toxin–Antitoxin System.” Current Genetics. Springer, 2019. https://doi.org/10.1007/s00294-018-0879-8.","mla":"Nikolic, Nela. “Autoregulation of Bacterial Gene Expression: Lessons from the MazEF Toxin–Antitoxin System.” Current Genetics, vol. 65, no. 1, Springer, 2019, pp. 133–38, doi:10.1007/s00294-018-0879-8.","short":"N. Nikolic, Current Genetics 65 (2019) 133–138."},"page":"133-138","abstract":[{"lang":"eng","text":"Autoregulation is the direct modulation of gene expression by the product of the corresponding gene. Autoregulation of bacterial gene expression has been mostly studied at the transcriptional level, when a protein acts as the cognate transcriptional repressor. A recent study investigating dynamics of the bacterial toxin–antitoxin MazEF system has shown how autoregulation at both the transcriptional and post-transcriptional levels affects the heterogeneity of Escherichia coli populations. Toxin–antitoxin systems hold a crucial but still elusive part in bacterial response to stress. This perspective highlights how these modules can also serve as a great model system for investigating basic concepts in gene regulation. However, as the genomic background and environmental conditions substantially influence toxin activation, it is important to study (auto)regulation of toxin–antitoxin systems in well-defined setups as well as in conditions that resemble the environmental niche."}],"issue":"1","type":"journal_article","oa_version":"Published Version","file":[{"date_updated":"2020-07-14T12:44:47Z","date_created":"2019-02-06T07:50:58Z","checksum":"6779708b0b632a1a6ed28c56f5161142","relation":"main_file","file_id":"5930","content_type":"application/pdf","file_size":776399,"creator":"dernst","file_name":"2019_CurrentGenetics_Nikolic.pdf","access_level":"open_access"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"138","title":"Autoregulation of bacterial gene expression: lessons from the MazEF toxin–antitoxin system","status":"public","ddc":["570"],"intvolume":" 65"},{"date_published":"2019-02-19T00:00:00Z","citation":{"short":"M. Lang, M. Shkolnikov, Proceedings of the National Academy of Sciences 116 (2019) 2821–2830.","mla":"Lang, Moritz, and Mikhail Shkolnikov. “Harmonic Dynamics of the Abelian Sandpile.” Proceedings of the National Academy of Sciences, vol. 116, no. 8, National Academy of Sciences, 2019, pp. 2821–30, doi:10.1073/pnas.1812015116.","chicago":"Lang, Moritz, and Mikhail Shkolnikov. “Harmonic Dynamics of the Abelian Sandpile.” Proceedings of the National Academy of Sciences. National Academy of Sciences, 2019. https://doi.org/10.1073/pnas.1812015116.","ama":"Lang M, Shkolnikov M. Harmonic dynamics of the Abelian sandpile. Proceedings of the National Academy of Sciences. 2019;116(8):2821-2830. doi:10.1073/pnas.1812015116","ieee":"M. Lang and M. Shkolnikov, “Harmonic dynamics of the Abelian sandpile,” Proceedings of the National Academy of Sciences, vol. 116, no. 8. National Academy of Sciences, pp. 2821–2830, 2019.","apa":"Lang, M., & Shkolnikov, M. (2019). Harmonic dynamics of the Abelian sandpile. Proceedings of the National Academy of Sciences. National Academy of Sciences. https://doi.org/10.1073/pnas.1812015116","ista":"Lang M, Shkolnikov M. 2019. Harmonic dynamics of the Abelian sandpile. Proceedings of the National Academy of Sciences. 116(8), 2821–2830."},"publication":"Proceedings of the National Academy of Sciences","page":"2821-2830","article_type":"original","article_processing_charge":"No","day":"19","scopus_import":"1","oa_version":"Published Version","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"196","intvolume":" 116","title":"Harmonic dynamics of the Abelian sandpile","status":"public","issue":"8","abstract":[{"text":"The abelian sandpile serves as a model to study self-organized criticality, a phenomenon occurring in biological, physical and social processes. The identity of the abelian group is a fractal composed of self-similar patches, and its limit is subject of extensive collaborative research. Here, we analyze the evolution of the sandpile identity under harmonic fields of different orders. We show that this evolution corresponds to periodic cycles through the abelian group characterized by the smooth transformation and apparent conservation of the patches constituting the identity. The dynamics induced by second and third order harmonics resemble smooth stretchings, respectively translations, of the identity, while the ones induced by fourth order harmonics resemble magnifications and rotations. Starting with order three, the dynamics pass through extended regions of seemingly random configurations which spontaneously reassemble into accentuated patterns. We show that the space of harmonic functions projects to the extended analogue of the sandpile group, thus providing a set of universal coordinates identifying configurations between different domains. Since the original sandpile group is a subgroup of the extended one, this directly implies that it admits a natural renormalization. Furthermore, we show that the harmonic fields can be induced by simple Markov processes, and that the corresponding stochastic dynamics show remarkable robustness over hundreds of periods. Finally, we encode information into seemingly random configurations, and decode this information with an algorithm requiring minimal prior knowledge. Our results suggest that harmonic fields might split the sandpile group into sub-sets showing different critical coefficients, and that it might be possible to extend the fractal structure of the identity beyond the boundaries of its domain. ","lang":"eng"}],"type":"journal_article","doi":"10.1073/pnas.1812015116","language":[{"iso":"eng"}],"oa":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1073/pnas.1812015116"}],"external_id":{"isi":["000459074400013"],"pmid":[" 30728300"],"arxiv":["1806.10823"]},"isi":1,"quality_controlled":"1","publication_identifier":{"eissn":["1091-6490"]},"month":"02","related_material":{"link":[{"relation":"press_release","description":"News on IST Webpage","url":"https://ist.ac.at/en/news/famous-sandpile-model-shown-to-move-like-a-traveling-sand-dune/"}]},"author":[{"full_name":"Lang, Moritz","first_name":"Moritz","last_name":"Lang","id":"29E0800A-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Shkolnikov, Mikhail","first_name":"Mikhail","last_name":"Shkolnikov","id":"35084A62-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4310-178X"}],"volume":116,"date_created":"2018-12-11T11:45:08Z","date_updated":"2023-09-11T14:09:34Z","pmid":1,"acknowledgement":"M.L. is grateful to the members of the C Guet and G Tkacik groups for valuable comments and support. M.S. is grateful to Nikita Kalinin for inspiring communications.\r\n","year":"2019","publisher":"National Academy of Sciences","department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"TaHa"}],"publication_status":"published"},{"keyword":["Escherichia coli","gene amplification","galactose","DOG","experimental evolution","Illumina sequence data","FACS data","microfluidics data"],"month":"11","day":"13","has_accepted_license":"1","article_processing_charge":"No","oa":1,"citation":{"ista":"Tomanek I. 2019. Data for the paper ‘Gene amplification as a form of population-level gene expression regulation’, Institute of Science and Technology Austria, 10.15479/AT:ISTA:7016.","apa":"Tomanek, I. (2019). Data for the paper “Gene amplification as a form of population-level gene expression regulation.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7016","ieee":"I. Tomanek, “Data for the paper ‘Gene amplification as a form of population-level gene expression regulation.’” Institute of Science and Technology Austria, 2019.","ama":"Tomanek I. Data for the paper “Gene amplification as a form of population-level gene expression regulation.” 2019. doi:10.15479/AT:ISTA:7016","chicago":"Tomanek, Isabella. “Data for the Paper ‘Gene Amplification as a Form of Population-Level Gene Expression Regulation.’” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:7016.","mla":"Tomanek, Isabella. Data for the Paper “Gene Amplification as a Form of Population-Level Gene Expression Regulation.” Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:7016.","short":"I. Tomanek, (2019)."},"date_published":"2019-11-13T00:00:00Z","doi":"10.15479/AT:ISTA:7016","type":"research_data","file_date_updated":"2020-07-14T12:47:47Z","abstract":[{"text":"Organisms cope with change by employing transcriptional regulators. However, when faced with rare environments, the evolution of transcriptional regulators and their promoters may be too slow. We ask whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. By real-time monitoring of gene copy number mutations in E. coli, we show that gene duplications and amplifications enable adaptation to fluctuating environments by rapidly generating copy number, and hence expression level, polymorphism. This ‘amplification-mediated gene expression tuning’ occurs on timescales similar to canonical gene regulation and can deal with rapid environmental changes. Mathematical modeling shows that amplifications also tune gene expression in stochastic environments where transcription factor-based schemes are hard to evolve or maintain. The fleeting nature of gene amplifications gives rise to a generic population-level mechanism that relies on genetic heterogeneity to rapidly tune expression of any gene, without leaving any genomic signature.","lang":"eng"}],"ddc":["576"],"status":"public","title":"Data for the paper \"Gene amplification as a form of population-level gene expression regulation\"","publisher":"Institute of Science and Technology Austria","department":[{"_id":"CaGu"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"7016","year":"2019","date_updated":"2024-02-21T12:45:25Z","date_created":"2019-11-13T09:07:31Z","file":[{"title":"Locus1_amplified","file_id":"7017","relation":"main_file","date_updated":"2020-07-14T12:47:47Z","date_created":"2019-11-13T08:52:21Z","checksum":"72441055043eda4cbf1398a422e2c118","description":"Illumina whole genome sequence data for Locus 1 - amplified.","file_name":"D8_S35_R2_001.fastq","access_level":"open_access","creator":"itomanek","content_type":"application/octet-stream","file_size":2456192500},{"relation":"main_file","file_id":"7018","title":"Locus1_ancestral","checksum":"a4ac50bf655d9c751f0305ade5c2ee16","date_created":"2019-11-13T08:52:59Z","date_updated":"2020-07-14T12:47:47Z","access_level":"open_access","file_name":"IT028_S11_R2_001.fastq","description":"Illumina whole genome sequence data for Locus 1 - 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The biophysics of transcription factor binding shapes gene regulation","ddc":["576","579"],"status":"public","abstract":[{"text":"Decades of studies have revealed the mechanisms of gene regulation in molecular detail. We make use of such well-described regulatory systems to explore how the molecular mechanisms of protein-protein and protein-DNA interactions shape the dynamics and evolution of gene regulation. \r\n\r\ni) We uncover how the biophysics of protein-DNA binding determines the potential of regulatory networks to evolve and adapt, which can be captured using a simple mathematical model. \r\nii) The evolution of regulatory connections can lead to a significant amount of crosstalk between binding proteins. We explore the effect of crosstalk on gene expression from a target promoter, which seems to be modulated through binding competition at non-specific DNA sites. \r\niii) We investigate how the very same biophysical characteristics as in i) can generate significant fitness costs for cells through global crosstalk, meaning non-specific DNA binding across the genomic background. \r\niv) Binding competition between proteins at a target promoter is a prevailing regulatory feature due to the prevalence of co-regulation at bacterial promoters. However, the dynamics of these systems are not always straightforward to determine even if the molecular mechanisms of regulation are known. A detailed model of the biophysical interactions reveals that interference between the regulatory proteins can constitute a new, generic form of system memory that records the history of the input signals at the promoter. \r\n\r\nWe demonstrate how the biophysics of protein-DNA binding can be harnessed to investigate the principles that shape and ultimately limit cellular gene regulation. These results provide a basis for studies of higher-level functionality, which arises from the underlying regulation. \r\n","lang":"eng"}],"type":"dissertation","alternative_title":["ISTA Thesis"],"date_published":"2019-05-03T00:00:00Z","citation":{"ista":"Igler C. 2019. On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation. Institute of Science and Technology Austria.","apa":"Igler, C. (2019). On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6371","ieee":"C. Igler, “On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation,” Institute of Science and Technology Austria, 2019.","ama":"Igler C. On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation. 2019. doi:10.15479/AT:ISTA:6371","chicago":"Igler, Claudia. “On the Nature of Gene Regulatory Design - The Biophysics of Transcription Factor Binding Shapes Gene Regulation.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6371.","mla":"Igler, Claudia. On the Nature of Gene Regulatory Design - The Biophysics of Transcription Factor Binding Shapes Gene Regulation. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6371.","short":"C. Igler, On the Nature of Gene Regulatory Design - The Biophysics of Transcription Factor Binding Shapes Gene Regulation, Institute of Science and Technology Austria, 2019."},"page":"152","day":"03","article_processing_charge":"No","has_accepted_license":"1","keyword":["gene regulation","biophysics","transcription factor binding","bacteria"]},{"month":"01","doi":"10.1007/978-1-4939-7792-5_15","language":[{"iso":"eng"}],"project":[{"grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425","name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7"}],"quality_controlled":"1","publist_id":"7574","ec_funded":1,"author":[{"full_name":"Misun, Patrick","first_name":"Patrick","last_name":"Misun"},{"full_name":"Birchler, Axel","last_name":"Birchler","first_name":"Axel"},{"full_name":"Lang, Moritz","first_name":"Moritz","last_name":"Lang","id":"29E0800A-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Hierlemann","first_name":"Andreas","full_name":"Hierlemann, Andreas"},{"first_name":"Olivier","last_name":"Frey","full_name":"Frey, Olivier"}],"volume":1771,"date_updated":"2021-01-12T07:40:42Z","date_created":"2018-12-11T11:45:43Z","year":"2018","acknowledgement":"This work was financially supported by FP7 of the EU through the project “Body on a chip,” ICT-FET-296257, and the ERC Advanced Grant “NeuroCMOS” (contract 267351), as well as by an individual Ambizione Grant 142440 from the Swiss National Science Foundation for Olivier Frey. The research leading to these results also received funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. [291734]. We would like to thank Alexander Stettler, ETH Zurich for his expertise and support in the cleanroom, and we acknowledge the Single Cell Unit of D-BSSE, ETH Zurich for assistance in microscopy issues. M.L. is grateful to the members of the Guet and Tkačik groups, IST Austria, for valuable comments and support.","publisher":"Springer","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publication_status":"published","day":"01","scopus_import":1,"date_published":"2018-01-01T00:00:00Z","citation":{"ieee":"P. Misun, A. Birchler, M. Lang, A. Hierlemann, and O. Frey, “Fabrication and operation of microfluidic hanging drop networks,” Methods in Molecular Biology, vol. 1771. Springer, pp. 183–202, 2018.","apa":"Misun, P., Birchler, A., Lang, M., Hierlemann, A., & Frey, O. (2018). Fabrication and operation of microfluidic hanging drop networks. Methods in Molecular Biology. Springer. https://doi.org/10.1007/978-1-4939-7792-5_15","ista":"Misun P, Birchler A, Lang M, Hierlemann A, Frey O. 2018. Fabrication and operation of microfluidic hanging drop networks. Methods in Molecular Biology. 1771, 183–202.","ama":"Misun P, Birchler A, Lang M, Hierlemann A, Frey O. Fabrication and operation of microfluidic hanging drop networks. Methods in Molecular Biology. 2018;1771:183-202. doi:10.1007/978-1-4939-7792-5_15","chicago":"Misun, Patrick, Axel Birchler, Moritz Lang, Andreas Hierlemann, and Olivier Frey. “Fabrication and Operation of Microfluidic Hanging Drop Networks.” Methods in Molecular Biology. Springer, 2018. https://doi.org/10.1007/978-1-4939-7792-5_15.","short":"P. Misun, A. Birchler, M. Lang, A. Hierlemann, O. Frey, Methods in Molecular Biology 1771 (2018) 183–202.","mla":"Misun, Patrick, et al. “Fabrication and Operation of Microfluidic Hanging Drop Networks.” Methods in Molecular Biology, vol. 1771, Springer, 2018, pp. 183–202, doi:10.1007/978-1-4939-7792-5_15."},"publication":"Methods in Molecular Biology","page":"183 - 202","abstract":[{"lang":"eng","text":"The hanging-drop network (HDN) is a technology platform based on a completely open microfluidic network at the bottom of an inverted, surface-patterned substrate. The platform is predominantly used for the formation, culturing, and interaction of self-assembled spherical microtissues (spheroids) under precisely controlled flow conditions. Here, we describe design, fabrication, and operation of microfluidic hanging-drop networks."}],"type":"journal_article","alternative_title":["MIMB"],"oa_version":"None","_id":"305","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":" 1771","title":"Fabrication and operation of microfluidic hanging drop networks","status":"public"},{"author":[{"full_name":"Oliveto, Pietro","last_name":"Oliveto","first_name":"Pietro"},{"full_name":"Paixao, Tiago","last_name":"Paixao","first_name":"Tiago","orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Jorge","last_name":"Pérez Heredia","full_name":"Pérez Heredia, Jorge"},{"last_name":"Sudholt","first_name":"Dirk","full_name":"Sudholt, Dirk"},{"first_name":"Barbora","last_name":"Trubenova","id":"42302D54-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6873-2967","full_name":"Trubenova, Barbora"}],"volume":80,"date_updated":"2023-09-11T14:11:35Z","date_created":"2018-12-11T11:48:09Z","year":"2018","department":[{"_id":"NiBa"},{"_id":"CaGu"}],"publisher":"Springer","publication_status":"published","ec_funded":1,"publist_id":"6957","file_date_updated":"2020-07-14T12:47:54Z","doi":"10.1007/s00453-017-0369-2","language":[{"iso":"eng"}],"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000428239300010"]},"project":[{"_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","grant_number":"618091","call_identifier":"FP7","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation"}],"quality_controlled":"1","isi":1,"month":"05","pubrep_id":"1014","oa_version":"Published Version","file":[{"access_level":"open_access","file_name":"IST-2018-1014-v1+1_2018_Paixao_Escape.pdf","content_type":"application/pdf","file_size":691245,"creator":"system","relation":"main_file","file_id":"4674","checksum":"7d92f5d7be81e387edeec4f06442791c","date_updated":"2020-07-14T12:47:54Z","date_created":"2018-12-12T10:08:14Z"}],"_id":"723","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","intvolume":" 80","status":"public","title":"How to escape local optima in black box optimisation when non elitism outperforms elitism","ddc":["576"],"issue":"5","abstract":[{"lang":"eng","text":"Escaping local optima is one of the major obstacles to function optimisation. Using the metaphor of a fitness landscape, local optima correspond to hills separated by fitness valleys that have to be overcome. We define a class of fitness valleys of tunable difficulty by considering their length, representing the Hamming path between the two optima and their depth, the drop in fitness. For this function class we present a runtime comparison between stochastic search algorithms using different search strategies. The (1+1) EA is a simple and well-studied evolutionary algorithm that has to jump across the valley to a point of higher fitness because it does not accept worsening moves (elitism). In contrast, the Metropolis algorithm and the Strong Selection Weak Mutation (SSWM) algorithm, a famous process in population genetics, are both able to cross the fitness valley by accepting worsening moves. We show that the runtime of the (1+1) EA depends critically on the length of the valley while the runtimes of the non-elitist algorithms depend crucially on the depth of the valley. Moreover, we show that both SSWM and Metropolis can also efficiently optimise a rugged function consisting of consecutive valleys."}],"type":"journal_article","date_published":"2018-05-01T00:00:00Z","citation":{"apa":"Oliveto, P., Paixao, T., Pérez Heredia, J., Sudholt, D., & Trubenova, B. (2018). How to escape local optima in black box optimisation when non elitism outperforms elitism. Algorithmica. Springer. https://doi.org/10.1007/s00453-017-0369-2","ieee":"P. Oliveto, T. Paixao, J. Pérez Heredia, D. Sudholt, and B. Trubenova, “How to escape local optima in black box optimisation when non elitism outperforms elitism,” Algorithmica, vol. 80, no. 5. Springer, pp. 1604–1633, 2018.","ista":"Oliveto P, Paixao T, Pérez Heredia J, Sudholt D, Trubenova B. 2018. How to escape local optima in black box optimisation when non elitism outperforms elitism. Algorithmica. 80(5), 1604–1633.","ama":"Oliveto P, Paixao T, Pérez Heredia J, Sudholt D, Trubenova B. How to escape local optima in black box optimisation when non elitism outperforms elitism. Algorithmica. 2018;80(5):1604-1633. doi:10.1007/s00453-017-0369-2","chicago":"Oliveto, Pietro, Tiago Paixao, Jorge Pérez Heredia, Dirk Sudholt, and Barbora Trubenova. “How to Escape Local Optima in Black Box Optimisation When Non Elitism Outperforms Elitism.” Algorithmica. Springer, 2018. https://doi.org/10.1007/s00453-017-0369-2.","short":"P. Oliveto, T. Paixao, J. Pérez Heredia, D. Sudholt, B. Trubenova, Algorithmica 80 (2018) 1604–1633.","mla":"Oliveto, Pietro, et al. “How to Escape Local Optima in Black Box Optimisation When Non Elitism Outperforms Elitism.” Algorithmica, vol. 80, no. 5, Springer, 2018, pp. 1604–33, doi:10.1007/s00453-017-0369-2."},"publication":"Algorithmica","page":"1604 - 1633","article_processing_charge":"No","has_accepted_license":"1","day":"01","scopus_import":"1"},{"month":"02","external_id":{"isi":["000425715100006"]},"isi":1,"quality_controlled":"1","doi":"10.1016/j.jbiotec.2018.01.008","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"Bio"}],"publist_id":"7317","year":"2018","acknowledgement":"We thank R Chait and M Lagator for sharing Bacillus subtilis CR_Y1 and pZS*_2R-cIPtet-Venus-Prm, respectively. We are grateful to T Pilizota and all members of the Guet lab for critically reading the manuscript. We also thank the Bioimaging facility at IST Austria for assistance using the FACSAria III system.\r\n\r\n","department":[{"_id":"CaGu"}],"publisher":"Elsevier","publication_status":"published","author":[{"first_name":"Kathrin","last_name":"Tomasek","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3768-877X","full_name":"Tomasek, Kathrin"},{"id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5396-4346","first_name":"Tobias","last_name":"Bergmiller","full_name":"Bergmiller, Tobias"},{"full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C"}],"volume":268,"date_created":"2018-12-11T11:46:50Z","date_updated":"2023-09-13T08:24:51Z","scopus_import":"1","article_processing_charge":"No","day":"20","citation":{"short":"K. Tomasek, T. Bergmiller, C.C. Guet, Journal of Biotechnology 268 (2018) 40–52.","mla":"Tomasek, Kathrin, et al. “Lack of Cations in Flow Cytometry Buffers Affect Fluorescence Signals by Reducing Membrane Stability and Viability of Escherichia Coli Strains.” Journal of Biotechnology, vol. 268, Elsevier, 2018, pp. 40–52, doi:10.1016/j.jbiotec.2018.01.008.","chicago":"Tomasek, Kathrin, Tobias Bergmiller, and Calin C Guet. “Lack of Cations in Flow Cytometry Buffers Affect Fluorescence Signals by Reducing Membrane Stability and Viability of Escherichia Coli Strains.” Journal of Biotechnology. Elsevier, 2018. https://doi.org/10.1016/j.jbiotec.2018.01.008.","ama":"Tomasek K, Bergmiller T, Guet CC. Lack of cations in flow cytometry buffers affect fluorescence signals by reducing membrane stability and viability of Escherichia coli strains. Journal of Biotechnology. 2018;268:40-52. doi:10.1016/j.jbiotec.2018.01.008","ieee":"K. Tomasek, T. Bergmiller, and C. C. Guet, “Lack of cations in flow cytometry buffers affect fluorescence signals by reducing membrane stability and viability of Escherichia coli strains,” Journal of Biotechnology, vol. 268. Elsevier, pp. 40–52, 2018.","apa":"Tomasek, K., Bergmiller, T., & Guet, C. C. (2018). Lack of cations in flow cytometry buffers affect fluorescence signals by reducing membrane stability and viability of Escherichia coli strains. Journal of Biotechnology. Elsevier. https://doi.org/10.1016/j.jbiotec.2018.01.008","ista":"Tomasek K, Bergmiller T, Guet CC. 2018. Lack of cations in flow cytometry buffers affect fluorescence signals by reducing membrane stability and viability of Escherichia coli strains. Journal of Biotechnology. 268, 40–52."},"publication":"Journal of Biotechnology","page":"40 - 52","date_published":"2018-02-20T00:00:00Z","type":"journal_article","abstract":[{"lang":"eng","text":"Buffers are essential for diluting bacterial cultures for flow cytometry analysis in order to study bacterial physiology and gene expression parameters based on fluorescence signals. Using a variety of constitutively expressed fluorescent proteins in Escherichia coli K-12 strain MG1655, we found strong artifactual changes in fluorescence levels after dilution into the commonly used flow cytometry buffer phosphate-buffered saline (PBS) and two other buffer solutions, Tris-HCl and M9 salts. These changes appeared very rapidly after dilution, and were linked to increased membrane permeability and loss in cell viability. We observed buffer-related effects in several different E. coli strains, K-12, C and W, but not E. coli B, which can be partially explained by differences in lipopolysaccharide (LPS) and outer membrane composition. Supplementing the buffers with divalent cations responsible for outer membrane stability, Mg2+ and Ca2+, preserved fluorescence signals, membrane integrity and viability of E. coli. Thus, stabilizing the bacterial outer membrane is essential for precise and unbiased measurements of fluorescence parameters using flow cytometry."}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"503","intvolume":" 268","title":"Lack of cations in flow cytometry buffers affect fluorescence signals by reducing membrane stability and viability of Escherichia coli strains","status":"public","oa_version":"None"},{"volume":16,"date_created":"2018-12-11T11:44:32Z","date_updated":"2023-09-13T08:45:41Z","related_material":{"record":[{"relation":"research_data","status":"public","id":"9810"}]},"author":[{"last_name":"Chaudhry","first_name":"Waqas","full_name":"Chaudhry, Waqas"},{"first_name":"Maros","last_name":"Pleska","id":"4569785E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7460-7479","full_name":"Pleska, Maros"},{"last_name":"Shah","first_name":"Nilang","full_name":"Shah, Nilang"},{"first_name":"Howard","last_name":"Weiss","full_name":"Weiss, Howard"},{"first_name":"Ingrid","last_name":"Mccall","full_name":"Mccall, Ingrid"},{"full_name":"Meyer, Justin","first_name":"Justin","last_name":"Meyer"},{"full_name":"Gupta, Animesh","first_name":"Animesh","last_name":"Gupta"},{"full_name":"Guet, Calin C","first_name":"Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052"},{"full_name":"Levin, Bruce","first_name":"Bruce","last_name":"Levin"}],"publisher":"Public Library of Science","department":[{"_id":"CaGu"}],"publication_status":"published","year":"2018","publist_id":"7972","file_date_updated":"2020-07-14T12:48:10Z","article_number":"2005971","language":[{"iso":"eng"}],"doi":"10.1371/journal.pbio.2005971","quality_controlled":"1","isi":1,"external_id":{"isi":["000443383300024"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"month":"08","file":[{"access_level":"open_access","file_name":"2018_Plos_Chaudhry.pdf","file_size":4007095,"content_type":"application/pdf","creator":"dernst","relation":"main_file","file_id":"5706","checksum":"527076f78265cd4ea192cd1569851587","date_updated":"2020-07-14T12:48:10Z","date_created":"2018-12-17T12:55:31Z"}],"oa_version":"Published Version","intvolume":" 16","status":"public","title":"Leaky resistance and the conditions for the existence of lytic bacteriophage","ddc":["570"],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"82","issue":"8","abstract":[{"lang":"eng","text":"In experimental cultures, when bacteria are mixed with lytic (virulent) bacteriophage, bacterial cells resistant to the phage commonly emerge and become the dominant population of bacteria. Following the ascent of resistant mutants, the densities of bacteria in these simple communities become limited by resources rather than the phage. Despite the evolution of resistant hosts, upon which the phage cannot replicate, the lytic phage population is most commonly maintained in an apparently stable state with the resistant bacteria. Several mechanisms have been put forward to account for this result. Here we report the results of population dynamic/evolution experiments with a virulent mutant of phage Lambda, λVIR, and Escherichia coli in serial transfer cultures. We show that, following the ascent of λVIR-resistant bacteria, λVIRis maintained in the majority of cases in maltose-limited minimal media and in all cases in nutrient-rich broth. Using mathematical models and experiments, we show that the dominant mechanism responsible for maintenance of λVIRin these resource-limited populations dominated by resistant E. coli is a high rate of either phenotypic or genetic transition from resistance to susceptibility—a hitherto undemonstrated mechanism we term "leaky resistance." We discuss the implications of leaky resistance to our understanding of the conditions for the maintenance of phage in populations of bacteria—their “existence conditions.”."}],"type":"journal_article","date_published":"2018-08-16T00:00:00Z","citation":{"ieee":"W. Chaudhry et al., “Leaky resistance and the conditions for the existence of lytic bacteriophage,” PLoS Biology, vol. 16, no. 8. Public Library of Science, 2018.","apa":"Chaudhry, W., Pleska, M., Shah, N., Weiss, H., Mccall, I., Meyer, J., … Levin, B. (2018). Leaky resistance and the conditions for the existence of lytic bacteriophage. PLoS Biology. Public Library of Science. https://doi.org/10.1371/journal.pbio.2005971","ista":"Chaudhry W, Pleska M, Shah N, Weiss H, Mccall I, Meyer J, Gupta A, Guet CC, Levin B. 2018. Leaky resistance and the conditions for the existence of lytic bacteriophage. PLoS Biology. 16(8), 2005971.","ama":"Chaudhry W, Pleska M, Shah N, et al. Leaky resistance and the conditions for the existence of lytic bacteriophage. PLoS Biology. 2018;16(8). doi:10.1371/journal.pbio.2005971","chicago":"Chaudhry, Waqas, Maros Pleska, Nilang Shah, Howard Weiss, Ingrid Mccall, Justin Meyer, Animesh Gupta, Calin C Guet, and Bruce Levin. “Leaky Resistance and the Conditions for the Existence of Lytic Bacteriophage.” PLoS Biology. Public Library of Science, 2018. https://doi.org/10.1371/journal.pbio.2005971.","short":"W. Chaudhry, M. Pleska, N. Shah, H. Weiss, I. Mccall, J. Meyer, A. Gupta, C.C. Guet, B. Levin, PLoS Biology 16 (2018).","mla":"Chaudhry, Waqas, et al. “Leaky Resistance and the Conditions for the Existence of Lytic Bacteriophage.” PLoS Biology, vol. 16, no. 8, 2005971, Public Library of Science, 2018, doi:10.1371/journal.pbio.2005971."},"publication":"PLoS Biology","has_accepted_license":"1","article_processing_charge":"Yes","day":"16","scopus_import":"1"},{"_id":"9810","year":"2018","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","department":[{"_id":"CaGu"}],"publisher":"Public Library of Science","title":"Numerical data used in figures","status":"public","related_material":{"record":[{"status":"public","relation":"used_in_publication","id":"82"}]},"author":[{"first_name":"Waqas","last_name":"Chaudhry","full_name":"Chaudhry, Waqas"},{"full_name":"Pleska, Maros","first_name":"Maros","last_name":"Pleska","id":"4569785E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7460-7479"},{"last_name":"Shah","first_name":"Nilang","full_name":"Shah, Nilang"},{"full_name":"Weiss, Howard","last_name":"Weiss","first_name":"Howard"},{"last_name":"Mccall","first_name":"Ingrid","full_name":"Mccall, Ingrid"},{"first_name":"Justin","last_name":"Meyer","full_name":"Meyer, Justin"},{"last_name":"Gupta","first_name":"Animesh","full_name":"Gupta, Animesh"},{"full_name":"Guet, Calin C","first_name":"Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052"},{"full_name":"Levin, Bruce","first_name":"Bruce","last_name":"Levin"}],"oa_version":"Published Version","date_updated":"2023-09-13T08:45:41Z","date_created":"2021-08-06T12:43:44Z","type":"research_data_reference","citation":{"ama":"Chaudhry W, Pleska M, Shah N, et al. Numerical data used in figures. 2018. doi:10.1371/journal.pbio.2005971.s008","apa":"Chaudhry, W., Pleska, M., Shah, N., Weiss, H., Mccall, I., Meyer, J., … Levin, B. (2018). Numerical data used in figures. Public Library of Science. https://doi.org/10.1371/journal.pbio.2005971.s008","ieee":"W. Chaudhry et al., “Numerical data used in figures.” Public Library of Science, 2018.","ista":"Chaudhry W, Pleska M, Shah N, Weiss H, Mccall I, Meyer J, Gupta A, Guet CC, Levin B. 2018. Numerical data used in figures, Public Library of Science, 10.1371/journal.pbio.2005971.s008.","short":"W. Chaudhry, M. Pleska, N. Shah, H. Weiss, I. Mccall, J. Meyer, A. Gupta, C.C. Guet, B. Levin, (2018).","mla":"Chaudhry, Waqas, et al. Numerical Data Used in Figures. Public Library of Science, 2018, doi:10.1371/journal.pbio.2005971.s008.","chicago":"Chaudhry, Waqas, Maros Pleska, Nilang Shah, Howard Weiss, Ingrid Mccall, Justin Meyer, Animesh Gupta, Calin C Guet, and Bruce Levin. “Numerical Data Used in Figures.” Public Library of Science, 2018. https://doi.org/10.1371/journal.pbio.2005971.s008."},"date_published":"2018-08-16T00:00:00Z","doi":"10.1371/journal.pbio.2005971.s008","article_processing_charge":"No","month":"08","day":"16"},{"ec_funded":1,"publist_id":"7364","date_updated":"2023-09-15T12:04:57Z","date_created":"2018-12-11T11:46:35Z","volume":2,"author":[{"full_name":"Pleska, Maros","orcid":"0000-0001-7460-7479","id":"4569785E-F248-11E8-B48F-1D18A9856A87","last_name":"Pleska","first_name":"Maros"},{"first_name":"Moritz","last_name":"Lang","id":"29E0800A-F248-11E8-B48F-1D18A9856A87","full_name":"Lang, Moritz"},{"full_name":"Refardt, Dominik","last_name":"Refardt","first_name":"Dominik"},{"last_name":"Levin","first_name":"Bruce","full_name":"Levin, Bruce"},{"orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C","full_name":"Guet, Calin C"}],"related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"202"}]},"publication_status":"published","publisher":"Springer Nature","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"year":"2018","month":"02","language":[{"iso":"eng"}],"doi":"10.1038/s41559-017-0424-z","quality_controlled":"1","isi":1,"project":[{"_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734","call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme"},{"grant_number":"RGY0079/2011","_id":"251BCBEC-B435-11E9-9278-68D0E5697425","name":"Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification Systems (HFSP Young investigators' grant)"},{"name":"Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level (DOC Fellowship)","_id":"251D65D8-B435-11E9-9278-68D0E5697425","grant_number":"24210"}],"external_id":{"isi":["000426516400027"]},"abstract":[{"lang":"eng","text":"Temperate bacteriophages integrate in bacterial genomes as prophages and represent an important source of genetic variation for bacterial evolution, frequently transmitting fitness-augmenting genes such as toxins responsible for virulence of major pathogens. However, only a fraction of bacteriophage infections are lysogenic and lead to prophage acquisition, whereas the majority are lytic and kill the infected bacteria. Unless able to discriminate lytic from lysogenic infections, mechanisms of immunity to bacteriophages are expected to act as a double-edged sword and increase the odds of survival at the cost of depriving bacteria of potentially beneficial prophages. We show that although restriction-modification systems as mechanisms of innate immunity prevent both lytic and lysogenic infections indiscriminately in individual bacteria, they increase the number of prophage-acquiring individuals at the population level. We find that this counterintuitive result is a consequence of phage-host population dynamics, in which restriction-modification systems delay infection onset until bacteria reach densities at which the probability of lysogeny increases. These results underscore the importance of population-level dynamics as a key factor modulating costs and benefits of immunity to temperate bacteriophages"}],"issue":"2","type":"journal_article","oa_version":"None","status":"public","title":"Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity","intvolume":" 2","_id":"457","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","day":"01","article_processing_charge":"No","scopus_import":"1","date_published":"2018-02-01T00:00:00Z","page":"359 - 366","publication":"Nature Ecology and Evolution","citation":{"ieee":"M. Pleska, M. Lang, D. Refardt, B. Levin, and C. C. Guet, “Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity,” Nature Ecology and Evolution, vol. 2, no. 2. Springer Nature, pp. 359–366, 2018.","apa":"Pleska, M., Lang, M., Refardt, D., Levin, B., & Guet, C. C. (2018). Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity. Nature Ecology and Evolution. Springer Nature. https://doi.org/10.1038/s41559-017-0424-z","ista":"Pleska M, Lang M, Refardt D, Levin B, Guet CC. 2018. Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity. Nature Ecology and Evolution. 2(2), 359–366.","ama":"Pleska M, Lang M, Refardt D, Levin B, Guet CC. Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity. Nature Ecology and Evolution. 2018;2(2):359-366. doi:10.1038/s41559-017-0424-z","chicago":"Pleska, Maros, Moritz Lang, Dominik Refardt, Bruce Levin, and Calin C Guet. “Phage-Host Population Dynamics Promotes Prophage Acquisition in Bacteria with Innate Immunity.” Nature Ecology and Evolution. Springer Nature, 2018. https://doi.org/10.1038/s41559-017-0424-z.","short":"M. Pleska, M. Lang, D. Refardt, B. Levin, C.C. Guet, Nature Ecology and Evolution 2 (2018) 359–366.","mla":"Pleska, Maros, et al. “Phage-Host Population Dynamics Promotes Prophage Acquisition in Bacteria with Innate Immunity.” Nature Ecology and Evolution, vol. 2, no. 2, Springer Nature, 2018, pp. 359–66, doi:10.1038/s41559-017-0424-z."}},{"_id":"5984","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","intvolume":" 9","ddc":["570"],"status":"public","title":"Optical functionalization of human class A orphan G-protein-coupled receptors","oa_version":"Published Version","file":[{"relation":"main_file","file_id":"5985","date_updated":"2020-07-14T12:47:14Z","date_created":"2019-02-14T10:58:29Z","checksum":"8325fcc194264af4749e662a73bf66b5","file_name":"2018_Springer_Morri.pdf","access_level":"open_access","file_size":1349914,"content_type":"application/pdf","creator":"kschuh"}],"type":"journal_article","issue":"1","abstract":[{"text":"G-protein-coupled receptors (GPCRs) form the largest receptor family, relay environmental stimuli to changes in cell behavior and represent prime drug targets. Many GPCRs are classified as orphan receptors because of the limited knowledge on their ligands and coupling to cellular signaling machineries. Here, we engineer a library of 63 chimeric receptors that contain the signaling domains of human orphan and understudied GPCRs functionally linked to the light-sensing domain of rhodopsin. Upon stimulation with visible light, we identify activation of canonical cell signaling pathways, including cAMP-, Ca2+-, MAPK/ERK-, and Rho-dependent pathways, downstream of the engineered receptors. For the human pseudogene GPR33, we resurrect a signaling function that supports its hypothesized role as a pathogen entry site. These results demonstrate that substituting unknown chemical activators with a light switch can reveal information about protein function and provide an optically controlled protein library for exploring the physiology and therapeutic potential of understudied GPCRs.","lang":"eng"}],"citation":{"chicago":"Morri, Maurizio, Inmaculada Sanchez-Romero, Alexandra-Madelaine Tichy, Stephanie Kainrath, Elliot J. Gerrard, Priscila Hirschfeld, Jan Schwarz, and Harald L Janovjak. “Optical Functionalization of Human Class A Orphan G-Protein-Coupled Receptors.” Nature Communications. Springer Nature, 2018. https://doi.org/10.1038/s41467-018-04342-1.","mla":"Morri, Maurizio, et al. “Optical Functionalization of Human Class A Orphan G-Protein-Coupled Receptors.” Nature Communications, vol. 9, no. 1, 1950, Springer Nature, 2018, doi:10.1038/s41467-018-04342-1.","short":"M. Morri, I. Sanchez-Romero, A.-M. Tichy, S. Kainrath, E.J. Gerrard, P. Hirschfeld, J. Schwarz, H.L. Janovjak, Nature Communications 9 (2018).","ista":"Morri M, Sanchez-Romero I, Tichy A-M, Kainrath S, Gerrard EJ, Hirschfeld P, Schwarz J, Janovjak HL. 2018. Optical functionalization of human class A orphan G-protein-coupled receptors. Nature Communications. 9(1), 1950.","ieee":"M. Morri et al., “Optical functionalization of human class A orphan G-protein-coupled receptors,” Nature Communications, vol. 9, no. 1. Springer Nature, 2018.","apa":"Morri, M., Sanchez-Romero, I., Tichy, A.-M., Kainrath, S., Gerrard, E. J., Hirschfeld, P., … Janovjak, H. L. (2018). Optical functionalization of human class A orphan G-protein-coupled receptors. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-018-04342-1","ama":"Morri M, Sanchez-Romero I, Tichy A-M, et al. Optical functionalization of human class A orphan G-protein-coupled receptors. Nature Communications. 2018;9(1). doi:10.1038/s41467-018-04342-1"},"publication":"Nature Communications","date_published":"2018-12-01T00:00:00Z","scopus_import":"1","article_processing_charge":"No","has_accepted_license":"1","day":"01","year":"2018","publisher":"Springer Nature","department":[{"_id":"HaJa"},{"_id":"CaGu"},{"_id":"MiSi"}],"publication_status":"published","author":[{"full_name":"Morri, Maurizio","last_name":"Morri","first_name":"Maurizio","id":"4863116E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Sanchez-Romero, Inmaculada","first_name":"Inmaculada","last_name":"Sanchez-Romero","id":"3D9C5D30-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Alexandra-Madelaine","last_name":"Tichy","id":"29D8BB2C-F248-11E8-B48F-1D18A9856A87","full_name":"Tichy, Alexandra-Madelaine"},{"full_name":"Kainrath, Stephanie","last_name":"Kainrath","first_name":"Stephanie","id":"32CFBA64-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Gerrard","first_name":"Elliot J.","full_name":"Gerrard, Elliot J."},{"full_name":"Hirschfeld, Priscila","id":"435ACB3A-F248-11E8-B48F-1D18A9856A87","last_name":"Hirschfeld","first_name":"Priscila"},{"full_name":"Schwarz, Jan","last_name":"Schwarz","first_name":"Jan","id":"346C1EC6-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Janovjak, Harald L","last_name":"Janovjak","first_name":"Harald L","orcid":"0000-0002-8023-9315","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87"}],"volume":9,"date_created":"2019-02-14T10:50:24Z","date_updated":"2023-09-19T14:29:32Z","article_number":"1950","ec_funded":1,"file_date_updated":"2020-07-14T12:47:14Z","external_id":{"isi":["000432280000006"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"project":[{"name":"Microbial Ion Channels for Synthetic Neurobiology","call_identifier":"FP7","_id":"25548C20-B435-11E9-9278-68D0E5697425","grant_number":"303564"},{"call_identifier":"FWF","name":"Molecular Drug Targets","_id":"255A6082-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24"}],"quality_controlled":"1","isi":1,"doi":"10.1038/s41467-018-04342-1","language":[{"iso":"eng"}],"publication_identifier":{"issn":["2041-1723"]},"month":"12"},{"publist_id":"8036","pmid":1,"year":"2018","publisher":"Oxford University Press","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publication_status":"published","author":[{"full_name":"Palmer, Adam","first_name":"Adam","last_name":"Palmer"},{"first_name":"Remy P","last_name":"Chait","id":"3464AE84-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0876-3187","full_name":"Chait, Remy P"},{"last_name":"Kishony","first_name":"Roy","full_name":"Kishony, Roy"}],"volume":35,"date_updated":"2023-10-17T11:51:06Z","date_created":"2018-12-11T11:44:11Z","publication_identifier":{"issn":["0737-4038"]},"month":"08","external_id":{"isi":["000452567200006"],"pmid":["30169679"]},"oa":1,"main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pubmed/30169679"}],"quality_controlled":"1","isi":1,"doi":"10.1093/molbev/msy163","language":[{"iso":"eng"}],"type":"journal_article","issue":"11","abstract":[{"lang":"eng","text":"Bacteria regulate genes to survive antibiotic stress, but regulation can be far from perfect. When regulation is not optimal, mutations that change gene expression can contribute to antibiotic resistance. It is not systematically understood to what extent natural gene regulation is or is not optimal for distinct antibiotics, and how changes in expression of specific genes quantitatively affect antibiotic resistance. Here we discover a simple quantitative relation between fitness, gene expression, and antibiotic potency, which rationalizes our observation that a multitude of genes and even innate antibiotic defense mechanisms have expression that is critically nonoptimal under antibiotic treatment. First, we developed a pooled-strain drug-diffusion assay and screened Escherichia coli overexpression and knockout libraries, finding that resistance to a range of 31 antibiotics could result from changing expression of a large and functionally diverse set of genes, in a primarily but not exclusively drug-specific manner. Second, by synthetically controlling the expression of single-drug and multidrug resistance genes, we observed that their fitness-expression functions changed dramatically under antibiotic treatment in accordance with a log-sensitivity relation. Thus, because many genes are nonoptimally expressed under antibiotic treatment, many regulatory mutations can contribute to resistance by altering expression and by activating latent defenses."}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"19","intvolume":" 35","status":"public","title":"Nonoptimal gene expression creates latent potential for antibiotic resistance","oa_version":"Submitted Version","scopus_import":"1","article_processing_charge":"No","day":"28","citation":{"ista":"Palmer A, Chait RP, Kishony R. 2018. Nonoptimal gene expression creates latent potential for antibiotic resistance. Molecular Biology and Evolution. 35(11), 2669–2684.","ieee":"A. Palmer, R. P. Chait, and R. Kishony, “Nonoptimal gene expression creates latent potential for antibiotic resistance,” Molecular Biology and Evolution, vol. 35, no. 11. Oxford University Press, pp. 2669–2684, 2018.","apa":"Palmer, A., Chait, R. P., & Kishony, R. (2018). Nonoptimal gene expression creates latent potential for antibiotic resistance. Molecular Biology and Evolution. Oxford University Press. https://doi.org/10.1093/molbev/msy163","ama":"Palmer A, Chait RP, Kishony R. Nonoptimal gene expression creates latent potential for antibiotic resistance. Molecular Biology and Evolution. 2018;35(11):2669-2684. doi:10.1093/molbev/msy163","chicago":"Palmer, Adam, Remy P Chait, and Roy Kishony. “Nonoptimal Gene Expression Creates Latent Potential for Antibiotic Resistance.” Molecular Biology and Evolution. Oxford University Press, 2018. https://doi.org/10.1093/molbev/msy163.","mla":"Palmer, Adam, et al. “Nonoptimal Gene Expression Creates Latent Potential for Antibiotic Resistance.” Molecular Biology and Evolution, vol. 35, no. 11, Oxford University Press, 2018, pp. 2669–84, doi:10.1093/molbev/msy163.","short":"A. Palmer, R.P. Chait, R. Kishony, Molecular Biology and Evolution 35 (2018) 2669–2684."},"publication":"Molecular Biology and Evolution","page":"2669 - 2684","article_type":"original","date_published":"2018-08-28T00:00:00Z"},{"scopus_import":"1","day":"06","article_processing_charge":"Yes (in subscription journal)","has_accepted_license":"1","page":"2918-2931","publication":"Nucleic Acids Research","citation":{"ama":"Nikolic N, Bergmiller T, Vandervelde A, Albanese T, Gelens L, Moll I. Autoregulation of mazEF expression underlies growth heterogeneity in bacterial populations. Nucleic Acids Research. 2018;46(6):2918-2931. doi:10.1093/nar/gky079","ista":"Nikolic N, Bergmiller T, Vandervelde A, Albanese T, Gelens L, Moll I. 2018. Autoregulation of mazEF expression underlies growth heterogeneity in bacterial populations. Nucleic Acids Research. 46(6), 2918–2931.","apa":"Nikolic, N., Bergmiller, T., Vandervelde, A., Albanese, T., Gelens, L., & Moll, I. (2018). Autoregulation of mazEF expression underlies growth heterogeneity in bacterial populations. Nucleic Acids Research. Oxford University Press. https://doi.org/10.1093/nar/gky079","ieee":"N. Nikolic, T. Bergmiller, A. Vandervelde, T. Albanese, L. Gelens, and I. Moll, “Autoregulation of mazEF expression underlies growth heterogeneity in bacterial populations,” Nucleic Acids Research, vol. 46, no. 6. Oxford University Press, pp. 2918–2931, 2018.","mla":"Nikolic, Nela, et al. “Autoregulation of MazEF Expression Underlies Growth Heterogeneity in Bacterial Populations.” Nucleic Acids Research, vol. 46, no. 6, Oxford University Press, 2018, pp. 2918–31, doi:10.1093/nar/gky079.","short":"N. Nikolic, T. Bergmiller, A. Vandervelde, T. Albanese, L. Gelens, I. Moll, Nucleic Acids Research 46 (2018) 2918–2931.","chicago":"Nikolic, Nela, Tobias Bergmiller, Alexandra Vandervelde, Tanino Albanese, Lendert Gelens, and Isabella Moll. “Autoregulation of MazEF Expression Underlies Growth Heterogeneity in Bacterial Populations.” Nucleic Acids Research. Oxford University Press, 2018. https://doi.org/10.1093/nar/gky079."},"date_published":"2018-04-06T00:00:00Z","type":"journal_article","abstract":[{"lang":"eng","text":"The MazF toxin sequence-specifically cleaves single-stranded RNA upon various stressful conditions, and it is activated as a part of the mazEF toxin–antitoxin module in Escherichia coli. Although autoregulation of mazEF expression through the MazE antitoxin-dependent transcriptional repression has been biochemically characterized, less is known about post-transcriptional autoregulation, as well as how both of these autoregulatory features affect growth of single cells during conditions that promote MazF production. Here, we demonstrate post-transcriptional autoregulation of mazF expression dynamics by MazF cleaving its own transcript. Single-cell analyses of bacterial populations during ectopic MazF production indicated that two-level autoregulation of mazEF expression influences cell-to-cell growth rate heterogeneity. The increase in growth rate heterogeneity is governed by the MazE antitoxin, and tuned by the MazF-dependent mazF mRNA cleavage. Also, both autoregulatory features grant rapid exit from the stress caused by mazF overexpression. Time-lapse microscopy revealed that MazF-mediated cleavage of mazF mRNA leads to increased temporal variability in length of individual cells during ectopic mazF overexpression, as explained by a stochastic model indicating that mazEF mRNA cleavage underlies temporal fluctuations in MazF levels during stress."}],"issue":"6","title":"Autoregulation of mazEF expression underlies growth heterogeneity in bacterial populations","status":"public","ddc":["576"],"intvolume":" 46","_id":"438","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa_version":"Published Version","file":[{"file_id":"5151","relation":"main_file","checksum":"3ff4f545c27e11a4cd20ccb30778793e","date_updated":"2020-07-14T12:46:27Z","date_created":"2018-12-12T10:15:30Z","access_level":"open_access","file_name":"IST-2018-971-v1+1_2018_Nikoloc_Autoregulation_of.pdf","creator":"system","file_size":5027978,"content_type":"application/pdf"}],"pubrep_id":"971","month":"04","isi":1,"quality_controlled":"1","project":[{"_id":"3AC91DDA-15DF-11EA-824D-93A3E7B544D1","name":"FWF Open Access Fund","call_identifier":"FWF"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000429009500021"]},"oa":1,"language":[{"iso":"eng"}],"doi":"10.1093/nar/gky079","file_date_updated":"2020-07-14T12:46:27Z","publication_status":"published","department":[{"_id":"CaGu"}],"publisher":"Oxford University Press","year":"2018","date_updated":"2024-02-21T13:44:45Z","date_created":"2018-12-11T11:46:29Z","volume":46,"author":[{"orcid":"0000-0001-9068-6090","id":"42D9CABC-F248-11E8-B48F-1D18A9856A87","last_name":"Nikolic","first_name":"Nela","full_name":"Nikolic, Nela"},{"full_name":"Bergmiller, Tobias","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5396-4346","first_name":"Tobias","last_name":"Bergmiller"},{"first_name":"Alexandra","last_name":"Vandervelde","full_name":"Vandervelde, Alexandra"},{"first_name":"Tanino","last_name":"Albanese","full_name":"Albanese, Tanino"},{"full_name":"Gelens, Lendert","first_name":"Lendert","last_name":"Gelens"},{"full_name":"Moll, Isabella","last_name":"Moll","first_name":"Isabella"}],"related_material":{"record":[{"id":"5569","status":"public","relation":"popular_science"}]}},{"abstract":[{"text":"Nela Nikolic, Tobias Bergmiller, Alexandra Vandervelde, Tanino G. Albanese, Lendert Gelens, and Isabella Moll (2018)\r\n“Autoregulation of mazEF expression underlies growth heterogeneity in bacterial populations” Nucleic Acids Research, doi: 10.15479/AT:ISTA:74;\r\nmicroscopy experiments by Tobias Bergmiller; image and data analysis by Nela Nikolic.","lang":"eng"}],"file_date_updated":"2020-07-14T12:47:04Z","publist_id":"7385","license":"https://creativecommons.org/publicdomain/zero/1.0/","datarep_id":"74","type":"research_data","author":[{"full_name":"Bergmiller, Tobias","orcid":"0000-0001-5396-4346","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","last_name":"Bergmiller","first_name":"Tobias"},{"full_name":"Nikolic, Nela","last_name":"Nikolic","first_name":"Nela","orcid":"0000-0001-9068-6090","id":"42D9CABC-F248-11E8-B48F-1D18A9856A87"}],"related_material":{"record":[{"id":"438","status":"public","relation":"research_paper"}]},"date_updated":"2024-02-21T13:44:45Z","date_created":"2018-12-12T12:31:35Z","oa_version":"Published Version","file":[{"date_created":"2018-12-12T13:04:39Z","date_updated":"2020-07-14T12:47:04Z","checksum":"61ebb92213cfffeba3ddbaff984b81af","file_id":"5637","relation":"main_file","creator":"system","file_size":3558703796,"content_type":"application/zip","file_name":"IST-2018-74-v1+2_15-11-05.zip","access_level":"open_access"},{"checksum":"bf26649af310ef6892d68576515cde6d","date_updated":"2020-07-14T12:47:04Z","date_created":"2018-12-12T13:04:55Z","relation":"main_file","file_id":"5638","content_type":"application/zip","file_size":1830422606,"creator":"system","access_level":"open_access","file_name":"IST-2018-74-v1+3_15-07-31.zip"},{"file_id":"5639","relation":"main_file","date_created":"2018-12-12T13:05:11Z","date_updated":"2020-07-14T12:47:04Z","checksum":"8e46eedce06f22acb2be1a9b9d3f56bd","file_name":"IST-2018-74-v1+4_Images_for_analysis.zip","access_level":"open_access","creator":"system","content_type":"application/zip","file_size":2140849248}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"5569","year":"2018","status":"public","ddc":["579"],"title":"Time-lapse microscopy data","department":[{"_id":"CaGu"}],"publisher":"Institute of Science and Technology Austria","month":"02","day":"07","article_processing_charge":"No","has_accepted_license":"1","keyword":["microscopy","microfluidics"],"doi":"10.15479/AT:ISTA:74","date_published":"2018-02-07T00:00:00Z","oa":1,"tmp":{"short":"CC0 (1.0)","image":"/images/cc_0.png","legal_code_url":"https://creativecommons.org/publicdomain/zero/1.0/legalcode","name":"Creative Commons Public Domain Dedication (CC0 1.0)"},"citation":{"chicago":"Bergmiller, Tobias, and Nela Nikolic. “Time-Lapse Microscopy Data.” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:74.","short":"T. Bergmiller, N. Nikolic, (2018).","mla":"Bergmiller, Tobias, and Nela Nikolic. Time-Lapse Microscopy Data. Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:74.","ieee":"T. Bergmiller and N. Nikolic, “Time-lapse microscopy data.” Institute of Science and Technology Austria, 2018.","apa":"Bergmiller, T., & Nikolic, N. (2018). Time-lapse microscopy data. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:74","ista":"Bergmiller T, Nikolic N. 2018. Time-lapse microscopy data, Institute of Science and Technology Austria, 10.15479/AT:ISTA:74.","ama":"Bergmiller T, Nikolic N. Time-lapse microscopy data. 2018. doi:10.15479/AT:ISTA:74"}},{"publication":"Nature Communications","citation":{"ista":"De Martino D, Mc AA, Bergmiller T, Guet CC, Tkačik G. 2018. Statistical mechanics for metabolic networks during steady state growth. Nature Communications. 9(1), 2988.","apa":"De Martino, D., Mc, A. A., Bergmiller, T., Guet, C. C., & Tkačik, G. (2018). Statistical mechanics for metabolic networks during steady state growth. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-018-05417-9","ieee":"D. De Martino, A. A. Mc, T. Bergmiller, C. C. Guet, and G. Tkačik, “Statistical mechanics for metabolic networks during steady state growth,” Nature Communications, vol. 9, no. 1. Springer Nature, 2018.","ama":"De Martino D, Mc AA, Bergmiller T, Guet CC, Tkačik G. Statistical mechanics for metabolic networks during steady state growth. Nature Communications. 2018;9(1). doi:10.1038/s41467-018-05417-9","chicago":"De Martino, Daniele, Andersson Anna Mc, Tobias Bergmiller, Calin C Guet, and Gašper Tkačik. “Statistical Mechanics for Metabolic Networks during Steady State Growth.” Nature Communications. Springer Nature, 2018. https://doi.org/10.1038/s41467-018-05417-9.","mla":"De Martino, Daniele, et al. “Statistical Mechanics for Metabolic Networks during Steady State Growth.” Nature Communications, vol. 9, no. 1, 2988, Springer Nature, 2018, doi:10.1038/s41467-018-05417-9.","short":"D. De Martino, A.A. Mc, T. Bergmiller, C.C. Guet, G. Tkačik, Nature Communications 9 (2018)."},"date_published":"2018-07-30T00:00:00Z","scopus_import":"1","day":"30","has_accepted_license":"1","article_processing_charge":"No","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"161","ddc":["570"],"status":"public","title":"Statistical mechanics for metabolic networks during steady state growth","intvolume":" 9","file":[{"file_id":"5728","relation":"main_file","date_updated":"2020-07-14T12:45:06Z","date_created":"2018-12-17T16:44:28Z","checksum":"3ba7ab27b27723c7dcf633e8fc1f8f18","file_name":"2018_NatureComm_DeMartino.pdf","access_level":"open_access","creator":"dernst","content_type":"application/pdf","file_size":1043205}],"oa_version":"Published Version","type":"journal_article","abstract":[{"lang":"eng","text":"Which properties of metabolic networks can be derived solely from stoichiometry? Predictive results have been obtained by flux balance analysis (FBA), by postulating that cells set metabolic fluxes to maximize growth rate. Here we consider a generalization of FBA to single-cell level using maximum entropy modeling, which we extend and test experimentally. Specifically, we define for Escherichia coli metabolism a flux distribution that yields the experimental growth rate: the model, containing FBA as a limit, provides a better match to measured fluxes and it makes a wide range of predictions: on flux variability, regulation, and correlations; on the relative importance of stoichiometry vs. optimization; on scaling relations for growth rate distributions. We validate the latter here with single-cell data at different sub-inhibitory antibiotic concentrations. The model quantifies growth optimization as emerging from the interplay of competitive dynamics in the population and regulation of metabolism at the level of single cells."}],"issue":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"external_id":{"isi":["000440149300021"]},"isi":1,"quality_controlled":"1","project":[{"call_identifier":"FWF","name":"Biophysics of information processing in gene regulation","grant_number":"P28844-B27","_id":"254E9036-B435-11E9-9278-68D0E5697425"},{"name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425"}],"doi":"10.1038/s41467-018-05417-9","language":[{"iso":"eng"}],"month":"07","year":"2018","publication_status":"published","department":[{"_id":"GaTk"},{"_id":"CaGu"}],"publisher":"Springer Nature","author":[{"full_name":"De Martino, Daniele","last_name":"De Martino","first_name":"Daniele","orcid":"0000-0002-5214-4706","id":"3FF5848A-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Mc, Andersson Anna","last_name":"Mc","first_name":"Andersson Anna"},{"full_name":"Bergmiller, Tobias","orcid":"0000-0001-5396-4346","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","last_name":"Bergmiller","first_name":"Tobias"},{"full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C"},{"full_name":"Tkacik, Gasper","first_name":"Gasper","last_name":"Tkacik","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455"}],"related_material":{"record":[{"status":"public","relation":"popular_science","id":"5587"}]},"date_updated":"2024-02-21T13:45:39Z","date_created":"2018-12-11T11:44:57Z","volume":9,"article_number":"2988","file_date_updated":"2020-07-14T12:45:06Z","ec_funded":1,"publist_id":"7760"},{"abstract":[{"text":"Expression of genes is a fundamental molecular phenotype that is subject to evolution by different types of mutations. Both the rate and the effect of mutations may depend on the DNA sequence context of a particular gene or a particular promoter sequence. In this thesis I investigate the nature of this dependence using simple genetic systems in Escherichia coli. With these systems I explore the evolution of constitutive gene expression from random starting sequences at different loci on the chromosome and at different locations in sequence space. First, I dissect chromosomal neighborhood effects that underlie locus-dependent differences in the potential of a gene under selection to become more highly expressed. Next, I find that the effects of point mutations in promoter sequences are dependent on sequence context, and that an existing energy matrix model performs poorly in predicting relative expression of unrelated sequences. Finally, I show that a substantial fraction of random sequences contain functional promoters and I present an extended thermodynamic model that predicts promoter strength in full sequence space. Taken together, these results provide new insights and guides on how to integrate information on sequence context to improve our qualitative and quantitative understanding of bacterial gene expression, with implications for rapid evolution of drug resistance, de novo evolution of genes, and horizontal gene transfer.","lang":"eng"}],"type":"dissertation","alternative_title":["ISTA Thesis"],"pubrep_id":"1059","file":[{"access_level":"closed","embargo_to":"open_access","file_name":"Thesis_Steinrueck_final.docx","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_size":9190845,"creator":"dernst","relation":"source_file","file_id":"5941","checksum":"413cbce1cd1debeae3abe2a25dbc70d1","date_updated":"2020-07-14T12:45:43Z","date_created":"2019-02-08T10:51:22Z"},{"checksum":"3def8b7854c8b42d643597ce0215efac","date_created":"2019-02-08T10:51:22Z","date_updated":"2021-02-11T11:17:14Z","file_id":"5942","embargo":"2019-11-02","relation":"main_file","creator":"dernst","file_size":7521973,"content_type":"application/pdf","access_level":"open_access","file_name":"Thesis_Steinrueck_final.pdf"}],"oa_version":"Published Version","_id":"26","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","status":"public","ddc":["576","579"],"title":"The influence of sequence context on the evolution of bacterial gene expression","day":"30","has_accepted_license":"1","article_processing_charge":"No","date_published":"2018-10-30T00:00:00Z","citation":{"mla":"Steinrück, Magdalena. The Influence of Sequence Context on the Evolution of Bacterial Gene Expression. Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th1059.","short":"M. Steinrück, The Influence of Sequence Context on the Evolution of Bacterial Gene Expression, Institute of Science and Technology Austria, 2018.","chicago":"Steinrück, Magdalena. “The Influence of Sequence Context on the Evolution of Bacterial Gene Expression.” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th1059.","ama":"Steinrück M. The influence of sequence context on the evolution of bacterial gene expression. 2018. doi:10.15479/AT:ISTA:th1059","ista":"Steinrück M. 2018. The influence of sequence context on the evolution of bacterial gene expression. Institute of Science and Technology Austria.","ieee":"M. Steinrück, “The influence of sequence context on the evolution of bacterial gene expression,” Institute of Science and Technology Austria, 2018.","apa":"Steinrück, M. (2018). The influence of sequence context on the evolution of bacterial gene expression. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th1059"},"page":"109","file_date_updated":"2021-02-11T11:17:14Z","publist_id":"8029","author":[{"first_name":"Magdalena","last_name":"Steinrück","id":"2C023F40-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1229-9719","full_name":"Steinrück, Magdalena"}],"related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"704"}]},"date_created":"2018-12-11T11:44:14Z","date_updated":"2023-09-07T12:48:43Z","year":"2018","publication_status":"published","publisher":"Institute of Science and Technology Austria","department":[{"_id":"CaGu"}],"month":"10","publication_identifier":{"issn":["2663-337X"]},"doi":"10.15479/AT:ISTA:th1059","degree_awarded":"PhD","supervisor":[{"last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C"}],"language":[{"iso":"eng"}],"oa":1},{"intvolume":" 2","title":"Evolutionary potential of transcription factors for gene regulatory rewiring","ddc":["570"],"status":"public","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"67","file":[{"access_level":"open_access","file_name":"2018_NatureEcology_Igler.pdf","creator":"dernst","content_type":"application/pdf","file_size":1135973,"file_id":"7830","relation":"main_file","checksum":"383a2e2c944a856e2e821ec8e7bf71b6","date_updated":"2020-07-14T12:47:37Z","date_created":"2020-05-14T11:28:52Z"}],"oa_version":"Submitted Version","type":"journal_article","issue":"10","abstract":[{"text":"Gene regulatory networks evolve through rewiring of individual components—that is, through changes in regulatory connections. However, the mechanistic basis of regulatory rewiring is poorly understood. Using a canonical gene regulatory system, we quantify the properties of transcription factors that determine the evolutionary potential for rewiring of regulatory connections: robustness, tunability and evolvability. In vivo repression measurements of two repressors at mutated operator sites reveal their contrasting evolutionary potential: while robustness and evolvability were positively correlated, both were in trade-off with tunability. Epistatic interactions between adjacent operators alleviated this trade-off. A thermodynamic model explains how the differences in robustness, tunability and evolvability arise from biophysical characteristics of repressor–DNA binding. The model also uncovers that the energy matrix, which describes how mutations affect repressor–DNA binding, encodes crucial information about the evolutionary potential of a repressor. The biophysical determinants of evolutionary potential for regulatory rewiring constitute a mechanistic framework for understanding network evolution.","lang":"eng"}],"page":"1633 - 1643","article_type":"original","citation":{"mla":"Igler, Claudia, et al. “Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring.” Nature Ecology and Evolution, vol. 2, no. 10, Nature Publishing Group, 2018, pp. 1633–43, doi:10.1038/s41559-018-0651-y.","short":"C. Igler, M. Lagator, G. Tkačik, J.P. Bollback, C.C. Guet, Nature Ecology and Evolution 2 (2018) 1633–1643.","chicago":"Igler, Claudia, Mato Lagator, Gašper Tkačik, Jonathan P Bollback, and Calin C Guet. “Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring.” Nature Ecology and Evolution. Nature Publishing Group, 2018. https://doi.org/10.1038/s41559-018-0651-y.","ama":"Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. Evolutionary potential of transcription factors for gene regulatory rewiring. Nature Ecology and Evolution. 2018;2(10):1633-1643. doi:10.1038/s41559-018-0651-y","ista":"Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. 2018. Evolutionary potential of transcription factors for gene regulatory rewiring. Nature Ecology and Evolution. 2(10), 1633–1643.","ieee":"C. Igler, M. Lagator, G. Tkačik, J. P. Bollback, and C. C. Guet, “Evolutionary potential of transcription factors for gene regulatory rewiring,” Nature Ecology and Evolution, vol. 2, no. 10. Nature Publishing Group, pp. 1633–1643, 2018.","apa":"Igler, C., Lagator, M., Tkačik, G., Bollback, J. P., & Guet, C. C. (2018). Evolutionary potential of transcription factors for gene regulatory rewiring. Nature Ecology and Evolution. Nature Publishing Group. https://doi.org/10.1038/s41559-018-0651-y"},"publication":"Nature Ecology and Evolution","date_published":"2018-09-10T00:00:00Z","scopus_import":"1","article_processing_charge":"No","has_accepted_license":"1","day":"10","publisher":"Nature Publishing Group","department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"JoBo"}],"publication_status":"published","year":"2018","volume":2,"date_updated":"2024-03-28T23:30:49Z","date_created":"2018-12-11T11:44:27Z","related_material":{"record":[{"relation":"popular_science","status":"public","id":"5585"},{"relation":"dissertation_contains","status":"public","id":"6371"}]},"author":[{"first_name":"Claudia","last_name":"Igler","id":"46613666-F248-11E8-B48F-1D18A9856A87","full_name":"Igler, Claudia"},{"full_name":"Lagator, Mato","last_name":"Lagator","first_name":"Mato","id":"345D25EC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Tkacik, Gasper","first_name":"Gasper","last_name":"Tkacik","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455"},{"full_name":"Bollback, Jonathan P","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4624-4612","first_name":"Jonathan P","last_name":"Bollback"},{"last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C"}],"ec_funded":1,"publist_id":"7987","file_date_updated":"2020-07-14T12:47:37Z","project":[{"name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425"},{"_id":"2578D616-B435-11E9-9278-68D0E5697425","grant_number":"648440","name":"Selective Barriers to Horizontal Gene Transfer","call_identifier":"H2020"},{"name":"Design principles underlying genetic switch architecture (DOC Fellowship)","_id":"251EE76E-B435-11E9-9278-68D0E5697425","grant_number":"24573"}],"isi":1,"quality_controlled":"1","external_id":{"isi":["000447947600021"]},"oa":1,"language":[{"iso":"eng"}],"doi":"10.1038/s41559-018-0651-y","month":"09"},{"day":"20","month":"07","article_processing_charge":"No","has_accepted_license":"1","project":[{"grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425","name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7"},{"grant_number":"648440","_id":"2578D616-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Selective Barriers to Horizontal Gene Transfer"},{"name":"Design principles underlying genetic switch architecture (DOC Fellowship)","_id":"251EE76E-B435-11E9-9278-68D0E5697425","grant_number":"24573"}],"tmp":{"short":"CC0 (1.0)","image":"/images/cc_0.png","legal_code_url":"https://creativecommons.org/publicdomain/zero/1.0/legalcode","name":"Creative Commons Public Domain Dedication (CC0 1.0)"},"citation":{"ama":"Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring. 2018. doi:10.15479/AT:ISTA:108","ista":"Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. 2018. Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring, Institute of Science and Technology Austria, 10.15479/AT:ISTA:108.","ieee":"C. Igler, M. Lagator, G. Tkačik, J. P. Bollback, and C. C. Guet, “Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring.” Institute of Science and Technology Austria, 2018.","apa":"Igler, C., Lagator, M., Tkačik, G., Bollback, J. P., & Guet, C. C. (2018). Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:108","mla":"Igler, Claudia, et al. Data for the Paper Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring. Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:108.","short":"C. Igler, M. Lagator, G. Tkačik, J.P. Bollback, C.C. Guet, (2018).","chicago":"Igler, Claudia, Mato Lagator, Gašper Tkačik, Jonathan P Bollback, and Calin C Guet. “Data for the Paper Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring.” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:108."},"oa":1,"date_published":"2018-07-20T00:00:00Z","doi":"10.15479/AT:ISTA:108","datarep_id":"108","type":"research_data","abstract":[{"text":"Mean repression values and standard error of the mean are given for all operator mutant libraries.","lang":"eng"}],"file_date_updated":"2020-07-14T12:47:07Z","ec_funded":1,"ddc":["576"],"status":"public","title":"Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publisher":"Institute of Science and Technology Austria","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"5585","year":"2018","date_created":"2018-12-12T12:31:40Z","date_updated":"2024-03-28T23:30:49Z","file":[{"access_level":"open_access","file_name":"IST-2018-108-v1+1_data_figures.xlsx","file_size":16507,"content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","creator":"system","relation":"main_file","file_id":"5611","checksum":"1435781526c77413802adee0d4583cce","date_updated":"2020-07-14T12:47:07Z","date_created":"2018-12-12T13:02:45Z"}],"oa_version":"Published Version","author":[{"id":"46613666-F248-11E8-B48F-1D18A9856A87","first_name":"Claudia","last_name":"Igler","full_name":"Igler, Claudia"},{"full_name":"Lagator, Mato","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","last_name":"Lagator","first_name":"Mato"},{"orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","last_name":"Tkacik","first_name":"Gasper","full_name":"Tkacik, Gasper"},{"orcid":"0000-0002-4624-4612","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","last_name":"Bollback","first_name":"Jonathan P","full_name":"Bollback, Jonathan P"},{"first_name":"Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C"}],"related_material":{"record":[{"relation":"research_paper","status":"public","id":"67"},{"id":"6371","relation":"research_paper","status":"public"}]}},{"file_date_updated":"2020-07-14T12:46:39Z","publist_id":"7279","ec_funded":1,"author":[{"id":"32CFBA64-F248-11E8-B48F-1D18A9856A87","last_name":"Kainrath","first_name":"Stephanie","full_name":"Kainrath, Stephanie"},{"full_name":"Stadler, Manuela","first_name":"Manuela","last_name":"Stadler"},{"full_name":"Gschaider-Reichhart, Eva","first_name":"Eva","last_name":"Gschaider-Reichhart","id":"3FEE232A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7218-7738"},{"last_name":"Distel","first_name":"Martin","full_name":"Distel, Martin"},{"first_name":"Harald L","last_name":"Janovjak","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8023-9315","full_name":"Janovjak, Harald L"}],"date_updated":"2021-01-12T08:01:33Z","date_created":"2018-12-11T11:47:02Z","volume":129,"year":"2017","publication_status":"published","department":[{"_id":"CaGu"},{"_id":"HaJa"}],"publisher":"Wiley","month":"05","doi":"10.1002/ange.201611998","language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"quality_controlled":"1","project":[{"grant_number":"303564","_id":"25548C20-B435-11E9-9278-68D0E5697425","name":"Microbial Ion Channels for Synthetic Neurobiology","call_identifier":"FP7"},{"name":"Molecular Drug Targets","call_identifier":"FWF","_id":"255A6082-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24"}],"abstract":[{"text":"Optogenetik und Photopharmakologie ermöglichen präzise räumliche und zeitliche Kontrolle von Proteinwechselwirkung und -funktion in Zellen und Tieren. Optogenetische Methoden, die auf grünes Licht ansprechen und zum Trennen von Proteinkomplexen geeignet sind, sind nichtweitläufig verfügbar, würden jedoch mehrfarbige Experimente zur Beantwortung von biologischen Fragestellungen ermöglichen. Hier demonstrieren wir die Verwendung von Cobalamin(Vitamin B12)-bindenden Domänen von bakteriellen CarH-Transkriptionsfaktoren zur Grünlicht-induzierten Dissoziation von Rezeptoren. Fusioniert mit dem Fibroblasten-W achstumsfaktor-Rezeptor 1 führten diese im Dunkeln in kultivierten Zellen zu Signalaktivität durch Oligomerisierung, welche durch Beleuchten umgehend aufgehoben wurde. In Zebrafischembryonen, die einen derartigen Rezeptor exprimieren, ermöglichte grünes Licht die Kontrolle über abnormale Signalaktivität während der Embryonalentwicklung. ","lang":"ger"}],"issue":"16","type":"journal_article","pubrep_id":"932","oa_version":"Published Version","file":[{"creator":"system","content_type":"application/pdf","file_size":1668557,"access_level":"open_access","file_name":"IST-2018-932-v1+1_Kainrath_et_al-2017-Angewandte_Chemie.pdf","checksum":"d66fee867e7cdbfa3fe276c2fb0778bb","date_created":"2018-12-12T10:13:24Z","date_updated":"2020-07-14T12:46:39Z","file_id":"5007","relation":"main_file"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"538","title":"Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen","status":"public","ddc":["571"],"intvolume":" 129","day":"20","has_accepted_license":"1","date_published":"2017-05-20T00:00:00Z","publication":"Angewandte Chemie","citation":{"ama":"Kainrath S, Stadler M, Gschaider-Reichhart E, Distel M, Janovjak HL. Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen. Angewandte Chemie. 2017;129(16):4679-4682. doi:10.1002/ange.201611998","ieee":"S. Kainrath, M. Stadler, E. Gschaider-Reichhart, M. Distel, and H. L. Janovjak, “Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen,” Angewandte Chemie, vol. 129, no. 16. Wiley, pp. 4679–4682, 2017.","apa":"Kainrath, S., Stadler, M., Gschaider-Reichhart, E., Distel, M., & Janovjak, H. L. (2017). Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen. Angewandte Chemie. Wiley. https://doi.org/10.1002/ange.201611998","ista":"Kainrath S, Stadler M, Gschaider-Reichhart E, Distel M, Janovjak HL. 2017. Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen. Angewandte Chemie. 129(16), 4679–4682.","short":"S. Kainrath, M. Stadler, E. Gschaider-Reichhart, M. Distel, H.L. Janovjak, Angewandte Chemie 129 (2017) 4679–4682.","mla":"Kainrath, Stephanie, et al. “Grünlicht-Induzierte Rezeptorinaktivierung Durch Cobalamin-Bindende Domänen.” Angewandte Chemie, vol. 129, no. 16, Wiley, 2017, pp. 4679–82, doi:10.1002/ange.201611998.","chicago":"Kainrath, Stephanie, Manuela Stadler, Eva Gschaider-Reichhart, Martin Distel, and Harald L Janovjak. “Grünlicht-Induzierte Rezeptorinaktivierung Durch Cobalamin-Bindende Domänen.” Angewandte Chemie. Wiley, 2017. https://doi.org/10.1002/ange.201611998."},"page":"4679 - 4682"},{"ec_funded":1,"publist_id":"7244","file_date_updated":"2020-07-14T12:47:10Z","article_number":"e28921","author":[{"full_name":"Lagator, Mato","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","first_name":"Mato","last_name":"Lagator"},{"full_name":"Sarikas, Srdjan","id":"35F0286E-F248-11E8-B48F-1D18A9856A87","first_name":"Srdjan","last_name":"Sarikas"},{"full_name":"Acar, Hande","orcid":"0000-0003-1986-9753","id":"2DDF136A-F248-11E8-B48F-1D18A9856A87","last_name":"Acar","first_name":"Hande"},{"full_name":"Bollback, Jonathan P","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4624-4612","first_name":"Jonathan P","last_name":"Bollback"},{"full_name":"Guet, Calin C","first_name":"Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052"}],"volume":6,"date_updated":"2021-01-12T08:03:15Z","date_created":"2018-12-11T11:47:14Z","year":"2017","department":[{"_id":"CaGu"},{"_id":"JoBo"},{"_id":"NiBa"}],"publisher":"eLife Sciences Publications","publication_status":"published","publication_identifier":{"issn":["2050084X"]},"month":"11","doi":"10.7554/eLife.28921","language":[{"iso":"eng"}],"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"project":[{"call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734"},{"grant_number":"648440","_id":"2578D616-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Selective Barriers to Horizontal Gene Transfer"}],"quality_controlled":"1","abstract":[{"lang":"eng","text":"Most phenotypes are determined by molecular systems composed of specifically interacting molecules. However, unlike for individual components, little is known about the distributions of mutational effects of molecular systems as a whole. We ask how the distribution of mutational effects of a transcriptional regulatory system differs from the distributions of its components, by first independently, and then simultaneously, mutating a transcription factor and the associated promoter it represses. We find that the system distribution exhibits increased phenotypic variation compared to individual component distributions - an effect arising from intermolecular epistasis between the transcription factor and its DNA-binding site. In large part, this epistasis can be qualitatively attributed to the structure of the transcriptional regulatory system and could therefore be a common feature in prokaryotes. Counter-intuitively, intermolecular epistasis can alleviate the constraints of individual components, thereby increasing phenotypic variation that selection could act on and facilitating adaptive evolution. "}],"type":"journal_article","pubrep_id":"918","oa_version":"Published Version","file":[{"file_name":"IST-2017-918-v1+1_elife-28921-figures-v3.pdf","access_level":"open_access","creator":"system","content_type":"application/pdf","file_size":8453470,"file_id":"5096","relation":"main_file","date_created":"2018-12-12T10:14:42Z","date_updated":"2020-07-14T12:47:10Z","checksum":"273ab17f33305e4eaafd911ff88e7c5b"},{"date_updated":"2020-07-14T12:47:10Z","date_created":"2018-12-12T10:14:43Z","checksum":"b433f90576c7be597cd43367946f8e7f","relation":"main_file","file_id":"5097","content_type":"application/pdf","file_size":1953221,"creator":"system","file_name":"IST-2017-918-v1+2_elife-28921-v3.pdf","access_level":"open_access"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"570","intvolume":" 6","status":"public","title":"Regulatory network structure determines patterns of intermolecular epistasis","ddc":["576"],"has_accepted_license":"1","day":"13","scopus_import":1,"date_published":"2017-11-13T00:00:00Z","citation":{"mla":"Lagator, Mato, et al. “Regulatory Network Structure Determines Patterns of Intermolecular Epistasis.” ELife, vol. 6, e28921, eLife Sciences Publications, 2017, doi:10.7554/eLife.28921.","short":"M. Lagator, S. Sarikas, H. Acar, J.P. Bollback, C.C. Guet, ELife 6 (2017).","chicago":"Lagator, Mato, Srdjan Sarikas, Hande Acar, Jonathan P Bollback, and Calin C Guet. “Regulatory Network Structure Determines Patterns of Intermolecular Epistasis.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.28921.","ama":"Lagator M, Sarikas S, Acar H, Bollback JP, Guet CC. Regulatory network structure determines patterns of intermolecular epistasis. eLife. 2017;6. doi:10.7554/eLife.28921","ista":"Lagator M, Sarikas S, Acar H, Bollback JP, Guet CC. 2017. Regulatory network structure determines patterns of intermolecular epistasis. eLife. 6, e28921.","apa":"Lagator, M., Sarikas, S., Acar, H., Bollback, J. P., & Guet, C. C. (2017). Regulatory network structure determines patterns of intermolecular epistasis. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.28921","ieee":"M. Lagator, S. Sarikas, H. Acar, J. P. Bollback, and C. C. Guet, “Regulatory network structure determines patterns of intermolecular epistasis,” eLife, vol. 6. eLife Sciences Publications, 2017."},"publication":"eLife"},{"date_updated":"2021-01-12T08:06:15Z","date_created":"2018-12-11T11:47:30Z","volume":8,"author":[{"full_name":"Chait, Remy P","id":"3464AE84-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0876-3187","first_name":"Remy P","last_name":"Chait"},{"full_name":"Ruess, Jakob","id":"4A245D00-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1615-3282","first_name":"Jakob","last_name":"Ruess"},{"id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5396-4346","first_name":"Tobias","last_name":"Bergmiller","full_name":"Bergmiller, Tobias"},{"full_name":"Tkacik, Gasper","last_name":"Tkacik","first_name":"Gasper","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C"}],"publication_status":"published","publisher":"Nature Publishing Group","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"year":"2017","acknowledgement":"We are grateful to M. Lang, H. Janovjak, M. Khammash, A. Milias-Argeitis, M. Rullan, G. Batt, A. Bosma-Moody, Aryan, S. Leibler, and members of the Guet and Tkačik groups for helpful discussion, comments, and suggestions. We thank A. Moglich, T. Mathes, J. Tabor, and S. Schmidl for kind gifts of strains, and R. Hauschild, B. Knep, M. Lang, T. Asenov, E. Papusheva, T. Menner, T. Adletzberger, and J. Merrin for technical assistance. The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007–2013) under REA grant agreement no. [291734]. (to R.C. and J.R.), Austrian Science Fund grant FWF P28844 (to G.T.), and internal IST Austria Interdisciplinary Project Support. J.R. acknowledges support from the Agence Nationale de la Recherche (ANR) under Grant Nos. ANR-16-CE33-0018 (MEMIP), ANR-16-CE12-0025 (COGEX) and ANR-10-BINF-06-01 (ICEBERG).","file_date_updated":"2020-07-14T12:47:20Z","ec_funded":1,"publist_id":"7191","article_number":"1535","language":[{"iso":"eng"}],"doi":"10.1038/s41467-017-01683-1","quality_controlled":"1","project":[{"name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","name":"Biophysics of information processing in gene regulation","_id":"254E9036-B435-11E9-9278-68D0E5697425","grant_number":"P28844-B27"}],"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"month":"12","publication_identifier":{"issn":["20411723"]},"file":[{"relation":"main_file","file_id":"5190","date_created":"2018-12-12T10:16:05Z","date_updated":"2020-07-14T12:47:20Z","checksum":"44bb5d0229926c23a9955d9fe0f9723f","file_name":"IST-2017-911-v1+1_s41467-017-01683-1.pdf","access_level":"open_access","content_type":"application/pdf","file_size":1951699,"creator":"system"}],"oa_version":"Published Version","pubrep_id":"911","title":"Shaping bacterial population behavior through computer interfaced control of individual cells","ddc":["576","579"],"status":"public","intvolume":" 8","_id":"613","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","abstract":[{"lang":"eng","text":"Bacteria in groups vary individually, and interact with other bacteria and the environment to produce population-level patterns of gene expression. Investigating such behavior in detail requires measuring and controlling populations at the single-cell level alongside precisely specified interactions and environmental characteristics. Here we present an automated, programmable platform that combines image-based gene expression and growth measurements with on-line optogenetic expression control for hundreds of individual Escherichia coli cells over days, in a dynamically adjustable environment. This integrated platform broadly enables experiments that bridge individual and population behaviors. We demonstrate: (i) population structuring by independent closed-loop control of gene expression in many individual cells, (ii) cell-cell variation control during antibiotic perturbation, (iii) hybrid bio-digital circuits in single cells, and freely specifiable digital communication between individual bacteria. These examples showcase the potential for real-time integration of theoretical models with measurement and control of many individual cells to investigate and engineer microbial population behavior."}],"issue":"1","type":"journal_article","date_published":"2017-12-01T00:00:00Z","publication":"Nature Communications","citation":{"short":"R.P. Chait, J. Ruess, T. Bergmiller, G. Tkačik, C.C. Guet, Nature Communications 8 (2017).","mla":"Chait, Remy P., et al. “Shaping Bacterial Population Behavior through Computer Interfaced Control of Individual Cells.” Nature Communications, vol. 8, no. 1, 1535, Nature Publishing Group, 2017, doi:10.1038/s41467-017-01683-1.","chicago":"Chait, Remy P, Jakob Ruess, Tobias Bergmiller, Gašper Tkačik, and Calin C Guet. “Shaping Bacterial Population Behavior through Computer Interfaced Control of Individual Cells.” Nature Communications. Nature Publishing Group, 2017. https://doi.org/10.1038/s41467-017-01683-1.","ama":"Chait RP, Ruess J, Bergmiller T, Tkačik G, Guet CC. Shaping bacterial population behavior through computer interfaced control of individual cells. Nature Communications. 2017;8(1). doi:10.1038/s41467-017-01683-1","ieee":"R. P. Chait, J. Ruess, T. Bergmiller, G. Tkačik, and C. C. Guet, “Shaping bacterial population behavior through computer interfaced control of individual cells,” Nature Communications, vol. 8, no. 1. Nature Publishing Group, 2017.","apa":"Chait, R. P., Ruess, J., Bergmiller, T., Tkačik, G., & Guet, C. C. (2017). Shaping bacterial population behavior through computer interfaced control of individual cells. Nature Communications. Nature Publishing Group. https://doi.org/10.1038/s41467-017-01683-1","ista":"Chait RP, Ruess J, Bergmiller T, Tkačik G, Guet CC. 2017. Shaping bacterial population behavior through computer interfaced control of individual cells. Nature Communications. 8(1), 1535."},"day":"01","article_processing_charge":"Yes (in subscription journal)","has_accepted_license":"1","scopus_import":1},{"acknowledgement":"Austrian Science Fund (FWF): M1697, P22249; Swiss National Science Foundation (SNF): 145706; European Commission;FWF Special Research Program: RNA-REG F43","year":"2017","publication_status":"published","department":[{"_id":"CaGu"}],"publisher":"PeerJ","author":[{"last_name":"Nikolic","first_name":"Nela","orcid":"0000-0001-9068-6090","id":"42D9CABC-F248-11E8-B48F-1D18A9856A87","full_name":"Nikolic, Nela"},{"full_name":"Didara, Zrinka","first_name":"Zrinka","last_name":"Didara"},{"last_name":"Moll","first_name":"Isabella","full_name":"Moll, Isabella"}],"date_created":"2018-12-11T11:47:33Z","date_updated":"2021-01-12T08:06:48Z","volume":2017,"article_number":"3830","file_date_updated":"2020-07-14T12:47:24Z","publist_id":"7172","oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"quality_controlled":"1","doi":"10.7717/peerj.3830","language":[{"iso":"eng"}],"month":"09","publication_identifier":{"issn":["21678359"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"624","status":"public","title":"MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations","ddc":["579"],"intvolume":" 2017","pubrep_id":"909","oa_version":"Published Version","file":[{"file_name":"IST-2017-909-v1+1_peerj-3830.pdf","access_level":"open_access","creator":"system","file_size":682064,"content_type":"application/pdf","file_id":"4908","relation":"main_file","date_created":"2018-12-12T10:11:51Z","date_updated":"2020-07-14T12:47:24Z","checksum":"3d79ae6b6eabc90b0eaaed82ff3493b0"}],"type":"journal_article","abstract":[{"lang":"eng","text":"Bacteria adapt to adverse environmental conditions by altering gene expression patterns. Recently, a novel stress adaptation mechanism has been described that allows Escherichia coli to alter gene expression at the post-transcriptional level. The key player in this regulatory pathway is the endoribonuclease MazF, the toxin component of the toxin-antitoxin module mazEF that is triggered by various stressful conditions. In general, MazF degrades the majority of transcripts by cleaving at ACA sites, which results in the retardation of bacterial growth. Furthermore, MazF can process a small subset of mRNAs and render them leaderless by removing their ribosome binding site. MazF concomitantly modifies ribosomes, making them selective for the translation of leaderless mRNAs. In this study, we employed fluorescent reporter-systems to investigate mazEF expression during stressful conditions, and to infer consequences of the mRNA processing mediated by MazF on gene expression at the single-cell level. Our results suggest that mazEF transcription is maintained at low levels in single cells encountering adverse conditions, such as antibiotic stress or amino acid starvation. Moreover, using the grcA mRNA as a model for MazF-mediated mRNA processing, we found that MazF activation promotes heterogeneity in the grcA reporter expression, resulting in a subpopulation of cells with increased levels of GrcA reporter protein."}],"issue":"9","publication":"PeerJ","citation":{"ista":"Nikolic N, Didara Z, Moll I. 2017. MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations. PeerJ. 2017(9), 3830.","apa":"Nikolic, N., Didara, Z., & Moll, I. (2017). MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations. PeerJ. PeerJ. https://doi.org/10.7717/peerj.3830","ieee":"N. Nikolic, Z. Didara, and I. Moll, “MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations,” PeerJ, vol. 2017, no. 9. PeerJ, 2017.","ama":"Nikolic N, Didara Z, Moll I. MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations. PeerJ. 2017;2017(9). doi:10.7717/peerj.3830","chicago":"Nikolic, Nela, Zrinka Didara, and Isabella Moll. “MazF Activation Promotes Translational Heterogeneity of the GrcA MRNA in Escherichia Coli Populations.” PeerJ. PeerJ, 2017. https://doi.org/10.7717/peerj.3830.","mla":"Nikolic, Nela, et al. “MazF Activation Promotes Translational Heterogeneity of the GrcA MRNA in Escherichia Coli Populations.” PeerJ, vol. 2017, no. 9, 3830, PeerJ, 2017, doi:10.7717/peerj.3830.","short":"N. Nikolic, Z. Didara, I. Moll, PeerJ 2017 (2017)."},"date_published":"2017-09-21T00:00:00Z","scopus_import":1,"day":"21","has_accepted_license":"1"},{"doi":"10.7554/eLife.23136","language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"quality_controlled":"1","month":"03","publication_identifier":{"issn":["2050084X"]},"author":[{"last_name":"Renault","first_name":"Thibaud","full_name":"Renault, Thibaud"},{"full_name":"Abraham, Anthony","first_name":"Anthony","last_name":"Abraham"},{"full_name":"Bergmiller, Tobias","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5396-4346","first_name":"Tobias","last_name":"Bergmiller"},{"first_name":"Guillaume","last_name":"Paradis","full_name":"Paradis, Guillaume"},{"first_name":"Simon","last_name":"Rainville","full_name":"Rainville, Simon"},{"full_name":"Charpentier, Emmanuelle","last_name":"Charpentier","first_name":"Emmanuelle"},{"orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C","full_name":"Guet, Calin C"},{"full_name":"Tu, Yuhai","first_name":"Yuhai","last_name":"Tu"},{"full_name":"Namba, Keiichi","first_name":"Keiichi","last_name":"Namba"},{"first_name":"James","last_name":"Keener","full_name":"Keener, James"},{"last_name":"Minamino","first_name":"Tohru","full_name":"Minamino, Tohru"},{"full_name":"Erhardt, Marc","first_name":"Marc","last_name":"Erhardt"}],"date_created":"2018-12-11T11:47:44Z","date_updated":"2021-01-12T08:07:55Z","volume":6,"year":"2017","publication_status":"published","department":[{"_id":"CaGu"}],"publisher":"eLife Sciences Publications","file_date_updated":"2020-07-14T12:47:33Z","publist_id":"7082","article_number":"e23136","date_published":"2017-03-06T00:00:00Z","publication":"eLife","citation":{"chicago":"Renault, Thibaud, Anthony Abraham, Tobias Bergmiller, Guillaume Paradis, Simon Rainville, Emmanuelle Charpentier, Calin C Guet, et al. “Bacterial Flagella Grow through an Injection Diffusion Mechanism.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.23136.","mla":"Renault, Thibaud, et al. “Bacterial Flagella Grow through an Injection Diffusion Mechanism.” ELife, vol. 6, e23136, eLife Sciences Publications, 2017, doi:10.7554/eLife.23136.","short":"T. Renault, A. Abraham, T. Bergmiller, G. Paradis, S. Rainville, E. Charpentier, C.C. Guet, Y. Tu, K. Namba, J. Keener, T. Minamino, M. Erhardt, ELife 6 (2017).","ista":"Renault T, Abraham A, Bergmiller T, Paradis G, Rainville S, Charpentier E, Guet CC, Tu Y, Namba K, Keener J, Minamino T, Erhardt M. 2017. Bacterial flagella grow through an injection diffusion mechanism. eLife. 6, e23136.","apa":"Renault, T., Abraham, A., Bergmiller, T., Paradis, G., Rainville, S., Charpentier, E., … Erhardt, M. (2017). Bacterial flagella grow through an injection diffusion mechanism. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.23136","ieee":"T. Renault et al., “Bacterial flagella grow through an injection diffusion mechanism,” eLife, vol. 6. eLife Sciences Publications, 2017.","ama":"Renault T, Abraham A, Bergmiller T, et al. Bacterial flagella grow through an injection diffusion mechanism. eLife. 2017;6. doi:10.7554/eLife.23136"},"day":"06","has_accepted_license":"1","scopus_import":1,"pubrep_id":"904","oa_version":"Published Version","file":[{"access_level":"open_access","file_name":"IST-2017-904-v1+1_elife-23136-v2.pdf","file_size":5520359,"content_type":"application/pdf","creator":"system","relation":"main_file","file_id":"4716","checksum":"39e1c3e82ddac83a30422fa72fa1a383","date_created":"2018-12-12T10:08:53Z","date_updated":"2020-07-14T12:47:33Z"},{"date_updated":"2020-07-14T12:47:33Z","date_created":"2018-12-12T10:08:54Z","checksum":"a6d542253028f52e00aa29739ddffe8f","relation":"main_file","file_id":"4717","file_size":11242920,"content_type":"application/pdf","creator":"system","file_name":"IST-2017-904-v1+2_elife-23136-figures-v2.pdf","access_level":"open_access"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"655","status":"public","ddc":["579"],"title":"Bacterial flagella grow through an injection diffusion mechanism","intvolume":" 6","abstract":[{"text":"The bacterial flagellum is a self-assembling nanomachine. The external flagellar filament, several times longer than a bacterial cell body, is made of a few tens of thousands subunits of a single protein: flagellin. A fundamental problem concerns the molecular mechanism of how the flagellum grows outside the cell, where no discernible energy source is available. Here, we monitored the dynamic assembly of individual flagella using in situ labelling and real-time immunostaining of elongating flagellar filaments. We report that the rate of flagellum growth, initially ~1,700 amino acids per second, decreases with length and that the previously proposed chain mechanism does not contribute to the filament elongation dynamics. Inhibition of the proton motive force-dependent export apparatus revealed a major contribution of substrate injection in driving filament elongation. The combination of experimental and mathematical evidence demonstrates that a simple, injection-diffusion mechanism controls bacterial flagella growth outside the cell.","lang":"eng"}],"type":"journal_article"},{"date_created":"2018-12-11T11:47:04Z","date_updated":"2023-02-23T14:10:34Z","volume":13,"author":[{"last_name":"Nikolic","first_name":"Nela","orcid":"0000-0001-9068-6090","id":"42D9CABC-F248-11E8-B48F-1D18A9856A87","full_name":"Nikolic, Nela"},{"full_name":"Schreiber, Frank","first_name":"Frank","last_name":"Schreiber"},{"full_name":"Dal Co, Alma","first_name":"Alma","last_name":"Dal Co"},{"full_name":"Kiviet, Daniel","first_name":"Daniel","last_name":"Kiviet"},{"last_name":"Bergmiller","first_name":"Tobias","orcid":"0000-0001-5396-4346","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","full_name":"Bergmiller, Tobias"},{"full_name":"Littmann, Sten","first_name":"Sten","last_name":"Littmann"},{"full_name":"Kuypers, Marcel","first_name":"Marcel","last_name":"Kuypers"},{"last_name":"Ackermann","first_name":"Martin","full_name":"Ackermann, Martin"}],"related_material":{"record":[{"status":"public","relation":"research_data","id":"9844"},{"relation":"research_data","status":"public","id":"9845"},{"id":"9846","relation":"research_data","status":"public"}]},"publication_status":"published","department":[{"_id":"CaGu"}],"publisher":"Public Library of Science","year":"2017","file_date_updated":"2020-07-14T12:46:46Z","publist_id":"7275","ec_funded":1,"article_number":"e1007122","language":[{"iso":"eng"}],"doi":"10.1371/journal.pgen.1007122","quality_controlled":"1","project":[{"name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"month":"12","publication_identifier":{"issn":["15537390"]},"file":[{"relation":"main_file","file_id":"5088","checksum":"22426d9382f21554bad5fa5967afcfd0","date_created":"2018-12-12T10:14:35Z","date_updated":"2020-07-14T12:46:46Z","access_level":"open_access","file_name":"IST-2018-959-v1+1_2017_Nikolic_Cell-to-cell.pdf","file_size":1308475,"content_type":"application/pdf","creator":"system"}],"oa_version":"Published Version","pubrep_id":"959","status":"public","title":"Cell-to-cell variation and specialization in sugar metabolism in clonal bacterial populations","ddc":["576","579"],"intvolume":" 13","_id":"541","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","abstract":[{"lang":"eng","text":"While we have good understanding of bacterial metabolism at the population level, we know little about the metabolic behavior of individual cells: do single cells in clonal populations sometimes specialize on different metabolic pathways? Such metabolic specialization could be driven by stochastic gene expression and could provide individual cells with growth benefits of specialization. We measured the degree of phenotypic specialization in two parallel metabolic pathways, the assimilation of glucose and arabinose. We grew Escherichia coli in chemostats, and used isotope-labeled sugars in combination with nanometer-scale secondary ion mass spectrometry and mathematical modeling to quantify sugar assimilation at the single-cell level. We found large variation in metabolic activities between single cells, both in absolute assimilation and in the degree to which individual cells specialize in the assimilation of different sugars. Analysis of transcriptional reporters indicated that this variation was at least partially based on cell-to-cell variation in gene expression. Metabolic differences between cells in clonal populations could potentially reduce metabolic incompatibilities between different pathways, and increase the rate at which parallel reactions can be performed."}],"issue":"12","type":"journal_article","date_published":"2017-12-18T00:00:00Z","publication":"PLoS Genetics","citation":{"apa":"Nikolic, N., Schreiber, F., Dal Co, A., Kiviet, D., Bergmiller, T., Littmann, S., … Ackermann, M. (2017). Cell-to-cell variation and specialization in sugar metabolism in clonal bacterial populations. PLoS Genetics. Public Library of Science. https://doi.org/10.1371/journal.pgen.1007122","ieee":"N. Nikolic et al., “Cell-to-cell variation and specialization in sugar metabolism in clonal bacterial populations,” PLoS Genetics, vol. 13, no. 12. Public Library of Science, 2017.","ista":"Nikolic N, Schreiber F, Dal Co A, Kiviet D, Bergmiller T, Littmann S, Kuypers M, Ackermann M. 2017. Cell-to-cell variation and specialization in sugar metabolism in clonal bacterial populations. PLoS Genetics. 13(12), e1007122.","ama":"Nikolic N, Schreiber F, Dal Co A, et al. Cell-to-cell variation and specialization in sugar metabolism in clonal bacterial populations. PLoS Genetics. 2017;13(12). doi:10.1371/journal.pgen.1007122","chicago":"Nikolic, Nela, Frank Schreiber, Alma Dal Co, Daniel Kiviet, Tobias Bergmiller, Sten Littmann, Marcel Kuypers, and Martin Ackermann. “Cell-to-Cell Variation and Specialization in Sugar Metabolism in Clonal Bacterial Populations.” PLoS Genetics. Public Library of Science, 2017. https://doi.org/10.1371/journal.pgen.1007122.","short":"N. Nikolic, F. Schreiber, A. Dal Co, D. Kiviet, T. Bergmiller, S. Littmann, M. Kuypers, M. Ackermann, PLoS Genetics 13 (2017).","mla":"Nikolic, Nela, et al. “Cell-to-Cell Variation and Specialization in Sugar Metabolism in Clonal Bacterial Populations.” PLoS Genetics, vol. 13, no. 12, e1007122, Public Library of Science, 2017, doi:10.1371/journal.pgen.1007122."},"day":"18","has_accepted_license":"1","scopus_import":1},{"department":[{"_id":"CaGu"}],"publisher":"The Royal Society","status":"public","title":"Supplementary materials and methods; Full data set from effects of mutations in phage restriction sites during escape from restriction–modification","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","_id":"9847","year":"2017","oa_version":"Published Version","date_created":"2021-08-09T13:54:38Z","date_updated":"2023-02-23T12:29:44Z","related_material":{"record":[{"id":"561","relation":"used_in_publication","status":"public"}]},"author":[{"full_name":"Pleska, Maros","id":"4569785E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7460-7479","first_name":"Maros","last_name":"Pleska"},{"full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet"}],"type":"research_data_reference","abstract":[{"lang":"eng","text":"information on culture conditions, phage mutagenesis, verification and lysate preparation; Raw data"}],"oa":1,"citation":{"ama":"Pleska M, Guet CC. Supplementary materials and methods; Full data set from effects of mutations in phage restriction sites during escape from restriction–modification. 2017. doi:10.6084/m9.figshare.5633917.v1","apa":"Pleska, M., & Guet, C. C. (2017). Supplementary materials and methods; Full data set from effects of mutations in phage restriction sites during escape from restriction–modification. The Royal Society. https://doi.org/10.6084/m9.figshare.5633917.v1","ieee":"M. Pleska and C. C. Guet, “Supplementary materials and methods; Full data set from effects of mutations in phage restriction sites during escape from restriction–modification.” The Royal Society, 2017.","ista":"Pleska M, Guet CC. 2017. Supplementary materials and methods; Full data set from effects of mutations in phage restriction sites during escape from restriction–modification, The Royal Society, 10.6084/m9.figshare.5633917.v1.","short":"M. Pleska, C.C. Guet, (2017).","mla":"Pleska, Maros, and Calin C. Guet. Supplementary Materials and Methods; Full Data Set from Effects of Mutations in Phage Restriction Sites during Escape from Restriction–Modification. 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Littmann, M. Kuypers, M. Ackermann, (2017).","mla":"Nikolic, Nela, et al. Source Data for Figures and Tables. Public Library of Science, 2017, doi:10.1371/journal.pgen.1007122.s018."},"doi":"10.1371/journal.pgen.1007122.s018","date_published":"2017-12-18T00:00:00Z","day":"18","month":"12","article_processing_charge":"No"},{"article_number":"20170646","publist_id":"7253","pmid":1,"acknowledgement":"This work was funded by an HFSP Young Investigators' grant RGY0079/2011 (C.C.G.). M.P. is a recipient of a DOC Fellowship of the Austrian Academy of Science at the Institute of Science and Technology Austria.","year":"2017","department":[{"_id":"CaGu"}],"publisher":"The Royal Society","publication_status":"published","related_material":{"record":[{"id":"9847","relation":"research_data","status":"public"},{"status":"public","relation":"dissertation_contains","id":"202"}]},"author":[{"last_name":"Pleska","first_name":"Maros","orcid":"0000-0001-7460-7479","id":"4569785E-F248-11E8-B48F-1D18A9856A87","full_name":"Pleska, Maros"},{"full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet"}],"volume":13,"date_created":"2018-12-11T11:47:11Z","date_updated":"2023-09-07T11:59:32Z","publication_identifier":{"issn":["1744-9561"]},"month":"12","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1098/rsbl.2017.0646"}],"external_id":{"pmid":["29237814"]},"oa":1,"project":[{"_id":"251BCBEC-B435-11E9-9278-68D0E5697425","grant_number":"RGY0079/2011","name":"Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification Systems (HFSP Young investigators' grant)"},{"name":"Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level (DOC Fellowship)","grant_number":"24210","_id":"251D65D8-B435-11E9-9278-68D0E5697425"}],"quality_controlled":"1","doi":"10.1098/rsbl.2017.0646","language":[{"iso":"eng"}],"type":"journal_article","issue":"12","abstract":[{"lang":"eng","text":"Restriction–modification systems are widespread genetic elements that protect bacteria from bacteriophage infections by recognizing and cleaving heterologous DNA at short, well-defined sequences called restriction sites. Bioinformatic evidence shows that restriction sites are significantly underrepresented in bacteriophage genomes, presumably because bacteriophages with fewer restriction sites are more likely to escape cleavage by restriction–modification systems. However, how mutations in restriction sites affect the likelihood of bacteriophage escape is unknown. Using the bacteriophage l and the restriction–modification system EcoRI, we show that while mutation effects at different restriction sites are unequal, they are independent. As a result, the probability of bacteriophage escape increases with each mutated restriction site. Our results experimentally support the role of restriction site avoidance as a response to selection imposed by restriction–modification systems and offer an insight into the events underlying the process of bacteriophage escape."}],"_id":"561","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":" 13","title":"Effects of mutations in phage restriction sites during escape from restriction–modification","status":"public","oa_version":"Published Version","scopus_import":"1","article_processing_charge":"No","day":"01","citation":{"ista":"Pleska M, Guet CC. 2017. Effects of mutations in phage restriction sites during escape from restriction–modification. Biology Letters. 13(12), 20170646.","apa":"Pleska, M., & Guet, C. C. (2017). Effects of mutations in phage restriction sites during escape from restriction–modification. Biology Letters. The Royal Society. https://doi.org/10.1098/rsbl.2017.0646","ieee":"M. Pleska and C. C. Guet, “Effects of mutations in phage restriction sites during escape from restriction–modification,” Biology Letters, vol. 13, no. 12. The Royal Society, 2017.","ama":"Pleska M, Guet CC. Effects of mutations in phage restriction sites during escape from restriction–modification. Biology Letters. 2017;13(12). doi:10.1098/rsbl.2017.0646","chicago":"Pleska, Maros, and Calin C Guet. “Effects of Mutations in Phage Restriction Sites during Escape from Restriction–Modification.” Biology Letters. The Royal Society, 2017. https://doi.org/10.1098/rsbl.2017.0646.","mla":"Pleska, Maros, and Calin C. Guet. “Effects of Mutations in Phage Restriction Sites during Escape from Restriction–Modification.” Biology Letters, vol. 13, no. 12, 20170646, The Royal Society, 2017, doi:10.1098/rsbl.2017.0646.","short":"M. Pleska, C.C. Guet, Biology Letters 13 (2017)."},"publication":"Biology Letters","article_type":"original","date_published":"2017-12-01T00:00:00Z"},{"project":[{"name":"Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level (DOC Fellowship)","_id":"251D65D8-B435-11E9-9278-68D0E5697425","grant_number":"24210"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"language":[{"iso":"eng"}],"degree_awarded":"PhD","supervisor":[{"first_name":"Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C"}],"doi":"10.15479/AT:ISTA:th_916","publication_identifier":{"issn":["2663-337X"]},"month":"10","publisher":"Institute of Science and Technology Austria","department":[{"_id":"CaGu"}],"publication_status":"published","acknowledgement":"During my PhD studies, I received help from many people, all of which unfortunately cannot be listed here. I thank them deeply and hope that I never made them regret their kindness.\r\nI would like to express my deepest gratitude to Călin Guet, who went far beyond his responsibilities as an advisor and was to me also a great mentor and a friend. Călin never questioned my potential or lacked compassion and I cannot thank him enough for cultivating in me an independent scientist. I was amazed by his ability to recognize the most fascinating scientific problems in objects of study that others would find mundane. I hope I adopted at least a fraction of this ability.\r\nI will be forever grateful to Bruce Levin for all his support and especially for giving me the best possible example of how one can practice excellent science with humor and style. Working with Bruce was a true privilege.\r\nI thank Jonathan Bollback and Gašper Tkačik for serving in my PhD committee and the Austrian Academy of Science for funding my PhD research via the DOC fellowship.\r\nI thank all our lab members: Tobias Bergmiller for his guidance, especially in the first years of my research, and for being a good friend throughout; Remy Chait for staying in the lab at unreasonable hours and for the good laughs at bad jokes we shared; Anna Staron for supportively listening to my whines whenever I had to run a gel; Magdalena Steinrück for her pioneering work in the lab; Kathrin Tomasek for keeping the entropic forces in check and for her FACS virtuosity; Isabella Tomanek for always being nice to me, no matter how much bench space I took from her.\r\nI thank all my collaborators: Reiko Okura and Yuichi Wakamoto for performing and analyzing the microfluidic experiments; Long Qian and Edo Kussell for their bioinformatics analysis; Dominik Refardt for the λ kan phage; Moritz for his help with the mathematical modeling. I thank Fabienne Jesse for her tireless editorial work on all our manuscripts.\r\nFinally, I would like to thank my family and especially my wife Edita, who sacrificed a lot so that I can pursue my goals and dreams.\r\n","year":"2017","date_created":"2018-12-11T11:45:10Z","date_updated":"2023-09-15T12:04:56Z","related_material":{"record":[{"id":"1243","status":"public","relation":"part_of_dissertation"},{"id":"561","status":"public","relation":"part_of_dissertation"},{"relation":"part_of_dissertation","status":"public","id":"457"}]},"author":[{"full_name":"Pleska, Maros","first_name":"Maros","last_name":"Pleska","id":"4569785E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7460-7479"}],"publist_id":"7711","file_date_updated":"2020-07-14T12:45:24Z","page":"126","citation":{"chicago":"Pleska, Maros. “Biology of Restriction-Modification Systems at the Single-Cell and Population Level.” Institute of Science and Technology Austria, 2017. https://doi.org/10.15479/AT:ISTA:th_916.","short":"M. Pleska, Biology of Restriction-Modification Systems at the Single-Cell and Population Level, Institute of Science and Technology Austria, 2017.","mla":"Pleska, Maros. Biology of Restriction-Modification Systems at the Single-Cell and Population Level. Institute of Science and Technology Austria, 2017, doi:10.15479/AT:ISTA:th_916.","apa":"Pleska, M. (2017). Biology of restriction-modification systems at the single-cell and population level. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_916","ieee":"M. Pleska, “Biology of restriction-modification systems at the single-cell and population level,” Institute of Science and Technology Austria, 2017.","ista":"Pleska M. 2017. Biology of restriction-modification systems at the single-cell and population level. Institute of Science and Technology Austria.","ama":"Pleska M. Biology of restriction-modification systems at the single-cell and population level. 2017. doi:10.15479/AT:ISTA:th_916"},"date_published":"2017-10-01T00:00:00Z","article_processing_charge":"No","has_accepted_license":"1","day":"01","status":"public","title":"Biology of restriction-modification systems at the single-cell and population level","ddc":["576","579"],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"202","oa_version":"Published Version","file":[{"access_level":"open_access","file_name":"IST-2018-916-v1+3_2017_Pleska_Maros_Thesis.pdf","creator":"system","file_size":18569590,"content_type":"application/pdf","file_id":"4710","relation":"main_file","checksum":"33cfb59674e91f82e3738396d3fb3776","date_created":"2018-12-12T10:08:48Z","date_updated":"2020-07-14T12:45:24Z"},{"file_id":"6204","relation":"source_file","date_created":"2019-04-05T08:33:14Z","date_updated":"2020-07-14T12:45:24Z","checksum":"dcc239968decb233e7f98cf1083d8c26","file_name":"2017_Pleska_Maros_Thesis.docx","access_level":"closed","creator":"dernst","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_size":2801649}],"pubrep_id":"916","alternative_title":["ISTA Thesis"],"type":"dissertation","abstract":[{"lang":"eng","text":"Restriction-modification (RM) represents the simplest and possibly the most widespread mechanism of self/non-self discrimination in nature. In order to provide bacteria with immunity against bacteriophages and other parasitic genetic elements, RM systems rely on a balance between two enzymes: the restriction enzyme, which cleaves non-self DNA at specific restriction sites, and the modification enzyme, which tags the host’s DNA as self and thus protects it from cleavage. In this thesis, I use population and single-cell level experiments in combination with mathematical modeling to study different aspects of the interplay between RM systems, bacteria and bacteriophages. First, I analyze how mutations in phage restriction sites affect the probability of phage escape – an inherently stochastic process, during which phages accidently get modified instead of restricted. Next, I use single-cell experiments to show that RM systems can, with a low probability, attack the genome of their bacterial host and that this primitive form of autoimmunity leads to a tradeoff between the evolutionary cost and benefit of RM systems. Finally, I investigate the nature of interactions between bacteria, RM systems and temperate bacteriophages to find that, as a consequence of phage escape and its impact on population dynamics, RM systems can promote acquisition of symbiotic bacteriophages, rather than limit it. The results presented here uncover new fundamental biological properties of RM systems and highlight their importance in the ecology and evolution of bacteria, bacteriophages and their interactions."}]},{"publist_id":"5898","ec_funded":1,"file_date_updated":"2020-07-14T12:44:46Z","publisher":"Springer","department":[{"_id":"ToHe"},{"_id":"CaGu"},{"_id":"NiBa"}],"publication_status":"published","year":"2017","volume":54,"date_created":"2018-12-11T11:51:32Z","date_updated":"2023-09-20T11:06:03Z","related_material":{"record":[{"id":"1835","relation":"earlier_version","status":"public"}]},"author":[{"orcid":"0000-0001-8180-0904","id":"3444EA5E-F248-11E8-B48F-1D18A9856A87","last_name":"Giacobbe","first_name":"Mirco","full_name":"Giacobbe, Mirco"},{"full_name":"Guet, Calin C","first_name":"Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052"},{"full_name":"Gupta, Ashutosh","id":"335E5684-F248-11E8-B48F-1D18A9856A87","first_name":"Ashutosh","last_name":"Gupta"},{"id":"40876CD8-F248-11E8-B48F-1D18A9856A87","orcid":"0000−0002−2985−7724","first_name":"Thomas A","last_name":"Henzinger","full_name":"Henzinger, Thomas A"},{"last_name":"Paixao","first_name":"Tiago","orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","full_name":"Paixao, Tiago"},{"last_name":"Petrov","first_name":"Tatjana","orcid":"0000-0002-9041-0905","id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","full_name":"Petrov, Tatjana"}],"publication_identifier":{"issn":["00015903"]},"month":"12","project":[{"name":"Quantitative Reactive Modeling","call_identifier":"FP7","_id":"25EE3708-B435-11E9-9278-68D0E5697425","grant_number":"267989"},{"name":"Rigorous Systems Engineering","call_identifier":"FWF","grant_number":"S 11407_N23","_id":"25832EC2-B435-11E9-9278-68D0E5697425"},{"_id":"25F42A32-B435-11E9-9278-68D0E5697425","grant_number":"Z211","name":"The Wittgenstein Prize","call_identifier":"FWF"},{"name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","call_identifier":"FP7","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","grant_number":"618091"},{"grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425","name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7"},{"name":"Limits to selection in biology and in evolutionary computation","call_identifier":"FP7","_id":"25B07788-B435-11E9-9278-68D0E5697425","grant_number":"250152"}],"isi":1,"quality_controlled":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"external_id":{"isi":["000414343200003"]},"language":[{"iso":"eng"}],"doi":"10.1007/s00236-016-0278-x","type":"journal_article","issue":"8","abstract":[{"lang":"eng","text":"The behaviour of gene regulatory networks (GRNs) is typically analysed using simulation-based statistical testing-like methods. In this paper, we demonstrate that we can replace this approach by a formal verification-like method that gives higher assurance and scalability. We focus on Wagner’s weighted GRN model with varying weights, which is used in evolutionary biology. In the model, weight parameters represent the gene interaction strength that may change due to genetic mutations. For a property of interest, we synthesise the constraints over the parameter space that represent the set of GRNs satisfying the property. We experimentally show that our parameter synthesis procedure computes the mutational robustness of GRNs—an important problem of interest in evolutionary biology—more efficiently than the classical simulation method. We specify the property in linear temporal logic. We employ symbolic bounded model checking and SMT solving to compute the space of GRNs that satisfy the property, which amounts to synthesizing a set of linear constraints on the weights."}],"intvolume":" 54","status":"public","title":"Model checking the evolution of gene regulatory networks","ddc":["006","576"],"_id":"1351","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa_version":"Published Version","file":[{"content_type":"application/pdf","file_size":755241,"creator":"dernst","access_level":"open_access","file_name":"2017_ActaInformatica_Giacobbe.pdf","checksum":"4e661d9135d7f8c342e8e258dee76f3e","date_updated":"2020-07-14T12:44:46Z","date_created":"2019-01-17T15:57:29Z","relation":"main_file","file_id":"5841"}],"pubrep_id":"649","scopus_import":"1","has_accepted_license":"1","article_processing_charge":"No","day":"01","page":"765 - 787","citation":{"chicago":"Giacobbe, Mirco, Calin C Guet, Ashutosh Gupta, Thomas A Henzinger, Tiago Paixao, and Tatjana Petrov. “Model Checking the Evolution of Gene Regulatory Networks.” Acta Informatica. Springer, 2017. https://doi.org/10.1007/s00236-016-0278-x.","mla":"Giacobbe, Mirco, et al. “Model Checking the Evolution of Gene Regulatory Networks.” Acta Informatica, vol. 54, no. 8, Springer, 2017, pp. 765–87, doi:10.1007/s00236-016-0278-x.","short":"M. Giacobbe, C.C. Guet, A. Gupta, T.A. Henzinger, T. Paixao, T. Petrov, Acta Informatica 54 (2017) 765–787.","ista":"Giacobbe M, Guet CC, Gupta A, Henzinger TA, Paixao T, Petrov T. 2017. Model checking the evolution of gene regulatory networks. Acta Informatica. 54(8), 765–787.","ieee":"M. Giacobbe, C. C. Guet, A. Gupta, T. A. Henzinger, T. Paixao, and T. Petrov, “Model checking the evolution of gene regulatory networks,” Acta Informatica, vol. 54, no. 8. Springer, pp. 765–787, 2017.","apa":"Giacobbe, M., Guet, C. C., Gupta, A., Henzinger, T. A., Paixao, T., & Petrov, T. (2017). Model checking the evolution of gene regulatory networks. Acta Informatica. Springer. https://doi.org/10.1007/s00236-016-0278-x","ama":"Giacobbe M, Guet CC, Gupta A, Henzinger TA, Paixao T, Petrov T. Model checking the evolution of gene regulatory networks. Acta Informatica. 2017;54(8):765-787. doi:10.1007/s00236-016-0278-x"},"publication":"Acta Informatica","date_published":"2017-12-01T00:00:00Z"},{"publication_status":"published","publisher":"Springer","department":[{"_id":"NiBa"},{"_id":"CaGu"}],"year":"2017","date_created":"2018-12-11T11:51:27Z","date_updated":"2023-09-20T11:14:42Z","volume":78,"author":[{"full_name":"Paixao, Tiago","first_name":"Tiago","last_name":"Paixao","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2361-3953"},{"first_name":"Jorge","last_name":"Pérez Heredia","full_name":"Pérez Heredia, Jorge"},{"full_name":"Sudholt, Dirk","last_name":"Sudholt","first_name":"Dirk"},{"orcid":"0000-0002-6873-2967","id":"42302D54-F248-11E8-B48F-1D18A9856A87","last_name":"Trubenova","first_name":"Barbora","full_name":"Trubenova, Barbora"}],"file_date_updated":"2020-07-14T12:44:44Z","publist_id":"5931","ec_funded":1,"isi":1,"quality_controlled":"1","project":[{"_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","grant_number":"618091","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","call_identifier":"FP7"}],"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000400379500013"]},"language":[{"iso":"eng"}],"doi":"10.1007/s00453-016-0212-1","month":"06","publication_identifier":{"issn":["01784617"]},"ddc":["576"],"title":"Towards a runtime comparison of natural and artificial evolution","status":"public","intvolume":" 78","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"1336","file":[{"creator":"system","file_size":710206,"content_type":"application/pdf","file_name":"IST-2016-658-v1+1_s00453-016-0212-1.pdf","access_level":"open_access","date_updated":"2020-07-14T12:44:44Z","date_created":"2018-12-12T10:10:19Z","checksum":"7873f665a0c598ac747c908f34cb14b9","file_id":"4805","relation":"main_file"}],"oa_version":"Published Version","pubrep_id":"658","type":"journal_article","abstract":[{"text":"Evolutionary algorithms (EAs) form a popular optimisation paradigm inspired by natural evolution. In recent years the field of evolutionary computation has developed a rigorous analytical theory to analyse the runtimes of EAs on many illustrative problems. Here we apply this theory to a simple model of natural evolution. In the Strong Selection Weak Mutation (SSWM) evolutionary regime the time between occurrences of new mutations is much longer than the time it takes for a mutated genotype to take over the population. In this situation, the population only contains copies of one genotype and evolution can be modelled as a stochastic process evolving one genotype by means of mutation and selection between the resident and the mutated genotype. The probability of accepting the mutated genotype then depends on the change in fitness. We study this process, SSWM, from an algorithmic perspective, quantifying its expected optimisation time for various parameters and investigating differences to a similar evolutionary algorithm, the well-known (1+1) EA. We show that SSWM can have a moderate advantage over the (1+1) EA at crossing fitness valleys and study an example where SSWM outperforms the (1+1) EA by taking advantage of information on the fitness gradient.","lang":"eng"}],"issue":"2","page":"681 - 713","publication":"Algorithmica","citation":{"chicago":"Paixao, Tiago, Jorge Pérez Heredia, Dirk Sudholt, and Barbora Trubenova. “Towards a Runtime Comparison of Natural and Artificial Evolution.” Algorithmica. Springer, 2017. https://doi.org/10.1007/s00453-016-0212-1.","mla":"Paixao, Tiago, et al. “Towards a Runtime Comparison of Natural and Artificial Evolution.” Algorithmica, vol. 78, no. 2, Springer, 2017, pp. 681–713, doi:10.1007/s00453-016-0212-1.","short":"T. Paixao, J. Pérez Heredia, D. Sudholt, B. Trubenova, Algorithmica 78 (2017) 681–713.","ista":"Paixao T, Pérez Heredia J, Sudholt D, Trubenova B. 2017. Towards a runtime comparison of natural and artificial evolution. Algorithmica. 78(2), 681–713.","apa":"Paixao, T., Pérez Heredia, J., Sudholt, D., & Trubenova, B. (2017). Towards a runtime comparison of natural and artificial evolution. Algorithmica. Springer. https://doi.org/10.1007/s00453-016-0212-1","ieee":"T. Paixao, J. Pérez Heredia, D. Sudholt, and B. Trubenova, “Towards a runtime comparison of natural and artificial evolution,” Algorithmica, vol. 78, no. 2. Springer, pp. 681–713, 2017.","ama":"Paixao T, Pérez Heredia J, Sudholt D, Trubenova B. Towards a runtime comparison of natural and artificial evolution. Algorithmica. 2017;78(2):681-713. doi:10.1007/s00453-016-0212-1"},"date_published":"2017-06-01T00:00:00Z","scopus_import":"1","day":"01","article_processing_charge":"No","has_accepted_license":"1"},{"publist_id":"6294","year":"2017","department":[{"_id":"CaGu"}],"publisher":"Wiley-Blackwell","publication_status":"published","author":[{"full_name":"Fang, Chong","last_name":"Fang","first_name":"Chong"},{"id":"3ABC5BA6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1391-8377","first_name":"Anna A","last_name":"Nagy-Staron","full_name":"Nagy-Staron, Anna A"},{"last_name":"Grafe","first_name":"Martin","full_name":"Grafe, Martin"},{"last_name":"Heermann","first_name":"Ralf","full_name":"Heermann, Ralf"},{"last_name":"Jung","first_name":"Kirsten","full_name":"Jung, Kirsten"},{"first_name":"Susanne","last_name":"Gebhard","full_name":"Gebhard, Susanne"},{"last_name":"Mascher","first_name":"Thorsten","full_name":"Mascher, Thorsten"}],"volume":104,"date_updated":"2023-09-20T11:48:43Z","date_created":"2018-12-11T11:50:03Z","publication_identifier":{"issn":[" 0950382X"]},"month":"04","external_id":{"isi":["000398059200002"]},"quality_controlled":"1","isi":1,"doi":"10.1111/mmi.13597","language":[{"iso":"eng"}],"type":"journal_article","issue":"1","abstract":[{"lang":"eng","text":"BceRS and PsdRS are paralogous two-component systems in Bacillus subtilis controlling the response to antimicrobial peptides. In the presence of extracellular bacitracin and nisin, respectively, the two response regulators (RRs) bind their target promoters, PbceA or PpsdA, resulting in a strong up-regulation of target gene expression and ultimately antibiotic resistance. Despite high sequence similarity between the RRs BceR and PsdR and their known binding sites, no cross-regulation has been observed between them. We therefore investigated the specificity determinants of PbceA and PpsdA that ensure the insulation of these two paralogous pathways at the RR–promoter interface. In vivo and in vitro analyses demonstrate that the regulatory regions within these two promoters contain three important elements: in addition to the known (main) binding site, we identified a linker region and a secondary binding site that are crucial for functionality. Initial binding to the high-affinity, low-specificity main binding site is a prerequisite for the subsequent highly specific binding of a second RR dimer to the low-affinity secondary binding site. In addition to this hierarchical cooperative binding, discrimination requires a competition of the two RRs for their respective binding site mediated by only slight differences in binding affinities."}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"1084","intvolume":" 104","status":"public","title":"Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis","oa_version":"None","scopus_import":"1","article_processing_charge":"No","day":"01","citation":{"chicago":"Fang, Chong, Anna A Nagy-Staron, Martin Grafe, Ralf Heermann, Kirsten Jung, Susanne Gebhard, and Thorsten Mascher. “Insulation and Wiring Specificity of BceR like Response Regulators and Their Target Promoters in Bacillus Subtilis.” Molecular Microbiology. Wiley-Blackwell, 2017. https://doi.org/10.1111/mmi.13597.","mla":"Fang, Chong, et al. “Insulation and Wiring Specificity of BceR like Response Regulators and Their Target Promoters in Bacillus Subtilis.” Molecular Microbiology, vol. 104, no. 1, Wiley-Blackwell, 2017, pp. 16–31, doi:10.1111/mmi.13597.","short":"C. Fang, A.A. Nagy-Staron, M. Grafe, R. Heermann, K. Jung, S. Gebhard, T. Mascher, Molecular Microbiology 104 (2017) 16–31.","ista":"Fang C, Nagy-Staron AA, Grafe M, Heermann R, Jung K, Gebhard S, Mascher T. 2017. Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis. Molecular Microbiology. 104(1), 16–31.","apa":"Fang, C., Nagy-Staron, A. A., Grafe, M., Heermann, R., Jung, K., Gebhard, S., & Mascher, T. (2017). Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis. Molecular Microbiology. Wiley-Blackwell. https://doi.org/10.1111/mmi.13597","ieee":"C. Fang et al., “Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis,” Molecular Microbiology, vol. 104, no. 1. Wiley-Blackwell, pp. 16–31, 2017.","ama":"Fang C, Nagy-Staron AA, Grafe M, et al. Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis. Molecular Microbiology. 2017;104(1):16-31. doi:10.1111/mmi.13597"},"publication":"Molecular Microbiology","page":"16 - 31","date_published":"2017-04-01T00:00:00Z"},{"month":"05","publication_identifier":{"issn":["2050084X"]},"language":[{"iso":"eng"}],"doi":"10.7554/eLife.25192","quality_controlled":"1","isi":1,"project":[{"name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","call_identifier":"FP7","grant_number":"618091","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425"},{"_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734","call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme"},{"grant_number":"648440","_id":"2578D616-B435-11E9-9278-68D0E5697425","name":"Selective Barriers to Horizontal Gene Transfer","call_identifier":"H2020"}],"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000404024800001"]},"file_date_updated":"2020-07-14T12:48:16Z","publist_id":"6460","ec_funded":1,"article_number":"e25192","date_updated":"2023-09-22T10:01:17Z","date_created":"2018-12-11T11:49:23Z","volume":6,"author":[{"full_name":"Lagator, Mato","first_name":"Mato","last_name":"Lagator","id":"345D25EC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Paixao, Tiago","last_name":"Paixao","first_name":"Tiago","orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Barton, Nicholas H","first_name":"Nicholas H","last_name":"Barton","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8548-5240"},{"id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4624-4612","first_name":"Jonathan P","last_name":"Bollback","full_name":"Bollback, Jonathan P"},{"last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C"}],"publication_status":"published","publisher":"eLife Sciences Publications","department":[{"_id":"CaGu"},{"_id":"NiBa"},{"_id":"JoBo"}],"year":"2017","day":"18","article_processing_charge":"Yes","has_accepted_license":"1","scopus_import":"1","date_published":"2017-05-18T00:00:00Z","publication":"eLife","citation":{"short":"M. Lagator, T. Paixao, N.H. Barton, J.P. Bollback, C.C. Guet, ELife 6 (2017).","mla":"Lagator, Mato, et al. “On the Mechanistic Nature of Epistasis in a Canonical Cis-Regulatory Element.” ELife, vol. 6, e25192, eLife Sciences Publications, 2017, doi:10.7554/eLife.25192.","chicago":"Lagator, Mato, Tiago Paixao, Nicholas H Barton, Jonathan P Bollback, and Calin C Guet. “On the Mechanistic Nature of Epistasis in a Canonical Cis-Regulatory Element.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.25192.","ama":"Lagator M, Paixao T, Barton NH, Bollback JP, Guet CC. On the mechanistic nature of epistasis in a canonical cis-regulatory element. eLife. 2017;6. doi:10.7554/eLife.25192","ieee":"M. Lagator, T. Paixao, N. H. Barton, J. P. Bollback, and C. C. Guet, “On the mechanistic nature of epistasis in a canonical cis-regulatory element,” eLife, vol. 6. eLife Sciences Publications, 2017.","apa":"Lagator, M., Paixao, T., Barton, N. H., Bollback, J. P., & Guet, C. C. (2017). On the mechanistic nature of epistasis in a canonical cis-regulatory element. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.25192","ista":"Lagator M, Paixao T, Barton NH, Bollback JP, Guet CC. 2017. On the mechanistic nature of epistasis in a canonical cis-regulatory element. eLife. 6, e25192."},"abstract":[{"text":"Understanding the relation between genotype and phenotype remains a major challenge. The difficulty of predicting individual mutation effects, and particularly the interactions between them, has prevented the development of a comprehensive theory that links genotypic changes to their phenotypic effects. We show that a general thermodynamic framework for gene regulation, based on a biophysical understanding of protein-DNA binding, accurately predicts the sign of epistasis in a canonical cis-regulatory element consisting of overlapping RNA polymerase and repressor binding sites. Sign and magnitude of individual mutation effects are sufficient to predict the sign of epistasis and its environmental dependence. Thus, the thermodynamic model offers the correct null prediction for epistasis between mutations across DNA-binding sites. Our results indicate that a predictive theory for the effects of cis-regulatory mutations is possible from first principles, as long as the essential molecular mechanisms and the constraints these impose on a biological system are accounted for.","lang":"eng"}],"type":"journal_article","file":[{"relation":"main_file","file_id":"5306","checksum":"59cdd4400fb41280122d414fea971546","date_created":"2018-12-12T10:17:49Z","date_updated":"2020-07-14T12:48:16Z","access_level":"open_access","file_name":"IST-2017-841-v1+1_elife-25192-v2.pdf","content_type":"application/pdf","file_size":2441529,"creator":"system"},{"content_type":"application/pdf","file_size":3752660,"creator":"system","file_name":"IST-2017-841-v1+2_elife-25192-figures-v2.pdf","access_level":"open_access","date_updated":"2020-07-14T12:48:16Z","date_created":"2018-12-12T10:17:50Z","checksum":"b69024880558b858eb8c5d47a92b6377","relation":"main_file","file_id":"5307"}],"oa_version":"Published Version","pubrep_id":"841","title":"On the mechanistic nature of epistasis in a canonical cis-regulatory element","status":"public","ddc":["576"],"intvolume":" 6","_id":"954","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1"},{"date_published":"2017-06-01T00:00:00Z","page":"46 - 55","citation":{"apa":"Lang, M., & Sontag, E. 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Sontag, Automatica 81C (2017) 46–55.","mla":"Lang, Moritz, and Eduardo Sontag. “Zeros of Nonlinear Systems with Input Invariances.” Automatica, vol. 81C, International Federation of Automatic Control, 2017, pp. 46–55, doi:10.1016/j.automatica.2017.03.030."},"publication":"Automatica","has_accepted_license":"1","article_processing_charge":"Yes (in subscription journal)","day":"01","scopus_import":"1","file":[{"access_level":"open_access","file_name":"IST-2017-813-v1+1_ZerosOfNonlinearSystems.pdf","file_size":1401954,"content_type":"application/pdf","creator":"system","relation":"main_file","file_id":"4884","date_created":"2018-12-12T10:11:29Z","date_updated":"2018-12-12T10:11:29Z"}],"oa_version":"Published Version","pubrep_id":"813","ddc":["000"],"status":"public","title":"Zeros of nonlinear systems with input invariances","_id":"1007","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","abstract":[{"text":"A nonlinear system possesses an invariance with respect to a set of transformations if its output dynamics remain invariant when transforming the input, and adjusting the initial condition accordingly. Most research has focused on invariances with respect to time-independent pointwise transformations like translational-invariance (u(t) -> u(t) + p, p in R) or scale-invariance (u(t) -> pu(t), p in R>0). In this article, we introduce the concept of s0-invariances with respect to continuous input transformations exponentially growing/decaying over time. We show that s0-invariant systems not only encompass linear time-invariant (LTI) systems with transfer functions having an irreducible zero at s0 in R, but also that the input/output relationship of nonlinear s0-invariant systems possesses properties well known from their linear counterparts. Furthermore, we extend the concept of s0-invariances to second- and higher-order s0-invariances, corresponding to invariances with respect to transformations of the time-derivatives of the input, and encompassing LTI systems with zeros of multiplicity two or higher. Finally, we show that nth-order 0-invariant systems realize – under mild conditions – nth-order nonlinear differential operators: when excited by an input of a characteristic functional form, the system’s output converges to a constant value only depending on the nth (nonlinear) derivative of the input.","lang":"eng"}],"type":"journal_article","language":[{"iso":"eng"}],"doi":"10.1016/j.automatica.2017.03.030","project":[{"name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425"}],"quality_controlled":"1","isi":1,"external_id":{"isi":["000403513900006"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"publication_identifier":{"issn":["0005-1098"]},"month":"06","volume":"81C","date_updated":"2023-10-17T08:51:18Z","date_created":"2018-12-11T11:49:39Z","author":[{"first_name":"Moritz","last_name":"Lang","id":"29E0800A-F248-11E8-B48F-1D18A9856A87","full_name":"Lang, Moritz"},{"full_name":"Sontag, Eduardo","first_name":"Eduardo","last_name":"Sontag"}],"department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publisher":"International Federation of Automatic Control","publication_status":"published","year":"2017","publist_id":"6391","ec_funded":1,"file_date_updated":"2018-12-12T10:11:29Z"},{"article_processing_charge":"No","has_accepted_license":"1","month":"04","day":"11","citation":{"chicago":"Steinrück, Magdalena, and Calin C Guet. “Fastq Files for ‘Complex Chromosomal Neighborhood Effects Determine the Adaptive Potential of a Gene under Selection.’” Institute of Science and Technology Austria, 2017. https://doi.org/10.15479/AT:ISTA:65.","short":"M. Steinrück, C.C. Guet, (2017).","mla":"Steinrück, Magdalena, and Calin C. Guet. Fastq Files for “Complex Chromosomal Neighborhood Effects Determine the Adaptive Potential of a Gene under Selection.” Institute of Science and Technology Austria, 2017, doi:10.15479/AT:ISTA:65.","apa":"Steinrück, M., & Guet, C. C. (2017). Fastq files for “Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:65","ieee":"M. Steinrück and C. C. Guet, “Fastq files for ‘Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection.’” Institute of Science and Technology Austria, 2017.","ista":"Steinrück M, Guet CC. 2017. Fastq files for ‘Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection’, Institute of Science and Technology Austria, 10.15479/AT:ISTA:65.","ama":"Steinrück M, Guet CC. 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Within the archive, different folders correspond to figures of the main text and the SI of the related publication.\r\nData is saved as plain text, with each folder containing a separate readme file describing the format. Typically, the data is from fluorescence microscopy measurements of single cells growing in a microfluidic \"mother machine\" device, and consists of relevant values (primarily arbitrary unit or normalized fluorescence measurements, and division times / growth rates) after raw microscopy images have been processed, segmented, and their features extracted, as described in the methods section of the related publication."}],"file_date_updated":"2020-07-14T12:47:03Z","type":"research_data","datarep_id":"53","related_material":{"record":[{"relation":"research_paper","status":"public","id":"665"}]},"author":[{"full_name":"Bergmiller, Tobias","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5396-4346","first_name":"Tobias","last_name":"Bergmiller"},{"first_name":"Anna M","last_name":"Andersson","id":"2B8A40DA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2912-6769","full_name":"Andersson, Anna M"},{"last_name":"Tomasek","first_name":"Kathrin","orcid":"0000-0003-3768-877X","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","full_name":"Tomasek, Kathrin"},{"full_name":"Balleza, Enrique","last_name":"Balleza","first_name":"Enrique"},{"last_name":"Kiviet","first_name":"Daniel","full_name":"Kiviet, Daniel"},{"id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9843-3522","first_name":"Robert","last_name":"Hauschild","full_name":"Hauschild, Robert"},{"full_name":"Tkacik, Gasper","first_name":"Gasper","last_name":"Tkacik","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455"},{"full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C"}],"oa_version":"Published Version","file":[{"file_id":"5603","relation":"main_file","checksum":"d77859af757ac8025c50c7b12b52eaf3","date_created":"2018-12-12T13:02:38Z","date_updated":"2020-07-14T12:47:03Z","access_level":"open_access","file_name":"IST-2017-53-v1+1_Data_MDE.zip","creator":"system","content_type":"application/zip","file_size":6773204}],"date_created":"2018-12-12T12:31:32Z","date_updated":"2024-02-21T13:49:00Z","_id":"5560","year":"2017","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Institute of Science and Technology Austria","department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"Bio"}],"status":"public","ddc":["571"],"title":"Biased partitioning of the multi-drug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity","has_accepted_license":"1","article_processing_charge":"No","month":"03","day":"10","keyword":["single cell microscopy","mother machine microfluidic device","AcrAB-TolC pump","multi-drug efflux","Escherichia coli"],"doi":"10.15479/AT:ISTA:53","date_published":"2017-03-10T00:00:00Z","tmp":{"short":"CC0 (1.0)","image":"/images/cc_0.png","legal_code_url":"https://creativecommons.org/publicdomain/zero/1.0/legalcode","name":"Creative Commons Public Domain Dedication (CC0 1.0)"},"oa":1,"citation":{"ama":"Bergmiller T, Andersson AM, Tomasek K, et al. Biased partitioning of the multi-drug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity. 2017. doi:10.15479/AT:ISTA:53","apa":"Bergmiller, T., Andersson, A. M., Tomasek, K., Balleza, E., Kiviet, D., Hauschild, R., … Guet, C. C. (2017). Biased partitioning of the multi-drug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:53","ieee":"T. Bergmiller et al., “Biased partitioning of the multi-drug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity.” Institute of Science and Technology Austria, 2017.","ista":"Bergmiller T, Andersson AM, Tomasek K, Balleza E, Kiviet D, Hauschild R, Tkačik G, Guet CC. 2017. Biased partitioning of the multi-drug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity, Institute of Science and Technology Austria, 10.15479/AT:ISTA:53.","short":"T. Bergmiller, A.M. Andersson, K. Tomasek, E. Balleza, D. Kiviet, R. Hauschild, G. Tkačik, C.C. Guet, (2017).","mla":"Bergmiller, Tobias, et al. Biased Partitioning of the Multi-Drug Efflux Pump AcrAB-TolC Underlies Long-Lived Phenotypic Heterogeneity. Institute of Science and Technology Austria, 2017, doi:10.15479/AT:ISTA:53.","chicago":"Bergmiller, Tobias, Anna M Andersson, Kathrin Tomasek, Enrique Balleza, Daniel Kiviet, Robert Hauschild, Gašper Tkačik, and Calin C Guet. “Biased Partitioning of the Multi-Drug Efflux Pump AcrAB-TolC Underlies Long-Lived Phenotypic Heterogeneity.” Institute of Science and Technology Austria, 2017. https://doi.org/10.15479/AT:ISTA:53."}},{"_id":"665","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":" 356","title":"Biased partitioning of the multidrug efflux pump AcrAB TolC underlies long lived phenotypic heterogeneity","status":"public","oa_version":"None","type":"journal_article","issue":"6335","abstract":[{"text":"The molecular mechanisms underlying phenotypic variation in isogenic bacterial populations remain poorly understood.We report that AcrAB-TolC, the main multidrug efflux pump of Escherichia coli, exhibits a strong partitioning bias for old cell poles by a segregation mechanism that is mediated by ternary AcrAB-TolC complex formation. Mother cells inheriting old poles are phenotypically distinct and display increased drug efflux activity relative to daughters. Consequently, we find systematic and long-lived growth differences between mother and daughter cells in the presence of subinhibitory drug concentrations. A simple model for biased partitioning predicts a population structure of long-lived and highly heterogeneous phenotypes. This straightforward mechanism of generating sustained growth rate differences at subinhibitory antibiotic concentrations has implications for understanding the emergence of multidrug resistance in bacteria.","lang":"eng"}],"citation":{"chicago":"Bergmiller, Tobias, Anna M Andersson, Kathrin Tomasek, Enrique Balleza, Daniel Kiviet, Robert Hauschild, Gašper Tkačik, and Calin C Guet. “Biased Partitioning of the Multidrug Efflux Pump AcrAB TolC Underlies Long Lived Phenotypic Heterogeneity.” Science. American Association for the Advancement of Science, 2017. https://doi.org/10.1126/science.aaf4762.","short":"T. Bergmiller, A.M. Andersson, K. Tomasek, E. Balleza, D. Kiviet, R. Hauschild, G. Tkačik, C.C. Guet, Science 356 (2017) 311–315.","mla":"Bergmiller, Tobias, et al. “Biased Partitioning of the Multidrug Efflux Pump AcrAB TolC Underlies Long Lived Phenotypic Heterogeneity.” Science, vol. 356, no. 6335, American Association for the Advancement of Science, 2017, pp. 311–15, doi:10.1126/science.aaf4762.","ieee":"T. Bergmiller et al., “Biased partitioning of the multidrug efflux pump AcrAB TolC underlies long lived phenotypic heterogeneity,” Science, vol. 356, no. 6335. American Association for the Advancement of Science, pp. 311–315, 2017.","apa":"Bergmiller, T., Andersson, A. M., Tomasek, K., Balleza, E., Kiviet, D., Hauschild, R., … Guet, C. C. (2017). Biased partitioning of the multidrug efflux pump AcrAB TolC underlies long lived phenotypic heterogeneity. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.aaf4762","ista":"Bergmiller T, Andersson AM, Tomasek K, Balleza E, Kiviet D, Hauschild R, Tkačik G, Guet CC. 2017. Biased partitioning of the multidrug efflux pump AcrAB TolC underlies long lived phenotypic heterogeneity. Science. 356(6335), 311–315.","ama":"Bergmiller T, Andersson AM, Tomasek K, et al. Biased partitioning of the multidrug efflux pump AcrAB TolC underlies long lived phenotypic heterogeneity. Science. 2017;356(6335):311-315. doi:10.1126/science.aaf4762"},"publication":"Science","page":"311 - 315","article_type":"original","date_published":"2017-04-21T00:00:00Z","scopus_import":1,"article_processing_charge":"No","day":"21","year":"2017","department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"Bio"}],"publisher":"American Association for the Advancement of Science","publication_status":"published","related_material":{"record":[{"id":"5560","relation":"popular_science","status":"public"}]},"author":[{"full_name":"Bergmiller, Tobias","last_name":"Bergmiller","first_name":"Tobias","orcid":"0000-0001-5396-4346","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Andersson, Anna M","first_name":"Anna M","last_name":"Andersson","id":"2B8A40DA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2912-6769"},{"full_name":"Tomasek, Kathrin","first_name":"Kathrin","last_name":"Tomasek","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3768-877X"},{"first_name":"Enrique","last_name":"Balleza","full_name":"Balleza, Enrique"},{"full_name":"Kiviet, Daniel","first_name":"Daniel","last_name":"Kiviet"},{"full_name":"Hauschild, Robert","last_name":"Hauschild","first_name":"Robert","orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Tkacik, Gasper","first_name":"Gasper","last_name":"Tkacik","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455"},{"full_name":"Guet, Calin C","first_name":"Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052"}],"volume":356,"date_created":"2018-12-11T11:47:48Z","date_updated":"2024-02-21T13:49:00Z","publist_id":"7064","project":[{"_id":"254E9036-B435-11E9-9278-68D0E5697425","grant_number":"P28844-B27","call_identifier":"FWF","name":"Biophysics of information processing in gene regulation"}],"quality_controlled":"1","doi":"10.1126/science.aaf4762","language":[{"iso":"eng"}],"publication_identifier":{"issn":["00368075"]},"month":"04"},{"type":"journal_article","issue":"16","abstract":[{"text":"Optogenetics and photopharmacology provide spatiotemporally precise control over protein interactions and protein function in cells and animals. Optogenetic methods that are sensitive to green light and can be used to break protein complexes are not broadly available but would enable multichromatic experiments with previously inaccessible biological targets. Herein, we repurposed cobalamin (vitamin B12) binding domains of bacterial CarH transcription factors for green-light-induced receptor dissociation. In cultured cells, we observed oligomerization-induced cell signaling for the fibroblast growth factor receptor 1 fused to cobalamin-binding domains in the dark that was rapidly eliminated upon illumination. In zebrafish embryos expressing fusion receptors, green light endowed control over aberrant fibroblast growth factor signaling during development. Green-light-induced domain dissociation and light-inactivated receptors will critically expand the optogenetic toolbox for control of biological processes.","lang":"eng"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"1028","intvolume":" 56","title":"Green-light-induced inactivation of receptor signaling using cobalamin-binding domains","status":"public","ddc":["540"],"oa_version":"Published Version","file":[{"file_id":"5845","relation":"main_file","success":1,"date_updated":"2019-01-18T09:39:55Z","date_created":"2019-01-18T09:39:55Z","access_level":"open_access","file_name":"2017_communications_Kainrath.pdf","creator":"dernst","content_type":"application/pdf","file_size":2614942}],"scopus_import":"1","article_processing_charge":"No","has_accepted_license":"1","day":"20","citation":{"ama":"Kainrath S, Stadler M, Gschaider-Reichhart E, Distel M, Janovjak HL. Green-light-induced inactivation of receptor signaling using cobalamin-binding domains. Angewandte Chemie - International Edition. 2017;56(16):4608-4611. doi:10.1002/anie.201611998","ista":"Kainrath S, Stadler M, Gschaider-Reichhart E, Distel M, Janovjak HL. 2017. Green-light-induced inactivation of receptor signaling using cobalamin-binding domains. Angewandte Chemie - International Edition. 56(16), 4608–4611.","apa":"Kainrath, S., Stadler, M., Gschaider-Reichhart, E., Distel, M., & Janovjak, H. L. (2017). Green-light-induced inactivation of receptor signaling using cobalamin-binding domains. Angewandte Chemie - International Edition. Wiley-Blackwell. https://doi.org/10.1002/anie.201611998","ieee":"S. Kainrath, M. Stadler, E. Gschaider-Reichhart, M. Distel, and H. L. Janovjak, “Green-light-induced inactivation of receptor signaling using cobalamin-binding domains,” Angewandte Chemie - International Edition, vol. 56, no. 16. Wiley-Blackwell, pp. 4608–4611, 2017.","mla":"Kainrath, Stephanie, et al. “Green-Light-Induced Inactivation of Receptor Signaling Using Cobalamin-Binding Domains.” Angewandte Chemie - International Edition, vol. 56, no. 16, Wiley-Blackwell, 2017, pp. 4608–11, doi:10.1002/anie.201611998.","short":"S. Kainrath, M. Stadler, E. Gschaider-Reichhart, M. Distel, H.L. Janovjak, Angewandte Chemie - International Edition 56 (2017) 4608–4611.","chicago":"Kainrath, Stephanie, Manuela Stadler, Eva Gschaider-Reichhart, Martin Distel, and Harald L Janovjak. “Green-Light-Induced Inactivation of Receptor Signaling Using Cobalamin-Binding Domains.” Angewandte Chemie - International Edition. Wiley-Blackwell, 2017. https://doi.org/10.1002/anie.201611998."},"publication":"Angewandte Chemie - International Edition","page":"4608-4611","date_published":"2017-03-20T00:00:00Z","ec_funded":1,"publist_id":"6362","file_date_updated":"2019-01-18T09:39:55Z","acknowledgement":"This work was supported by a grant from the European Unions Seventh Framework Programme (CIG-303564). E.R. was supported by the graduate program MolecularDrugTargets (Austrian Science Fund (FWF), W1232) and a FemTech fellowship (Austrian Research Promotion Agency, 3580812)","year":"2017","department":[{"_id":"CaGu"},{"_id":"HaJa"}],"publisher":"Wiley-Blackwell","publication_status":"published","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"418"},{"relation":"part_of_dissertation","status":"public","id":"7680"}]},"author":[{"full_name":"Kainrath, Stephanie","last_name":"Kainrath","first_name":"Stephanie","id":"32CFBA64-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Stadler","first_name":"Manuela","full_name":"Stadler, Manuela"},{"id":"3FEE232A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7218-7738","first_name":"Eva","last_name":"Gschaider-Reichhart","full_name":"Gschaider-Reichhart, Eva"},{"first_name":"Martin","last_name":"Distel","full_name":"Distel, Martin"},{"full_name":"Janovjak, Harald L","last_name":"Janovjak","first_name":"Harald L","orcid":"0000-0002-8023-9315","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87"}],"volume":56,"date_updated":"2024-03-28T23:30:13Z","date_created":"2018-12-11T11:49:46Z","publication_identifier":{"issn":["14337851"]},"month":"03","oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000398154000038"]},"project":[{"_id":"25548C20-B435-11E9-9278-68D0E5697425","grant_number":"303564","call_identifier":"FP7","name":"Microbial Ion Channels for Synthetic Neurobiology"},{"call_identifier":"FWF","name":"Molecular Drug Targets [do not use to be deleted]","_id":"26AA4EF2-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24"}],"isi":1,"quality_controlled":"1","doi":"10.1002/anie.201611998","language":[{"iso":"eng"}]},{"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"quality_controlled":"1","doi":"10.7554/eLife.25100","language":[{"iso":"eng"}],"publication_identifier":{"issn":["2050084X"]},"month":"07","year":"2017","publisher":"eLife Sciences Publications","department":[{"_id":"CaGu"}],"publication_status":"published","related_material":{"record":[{"status":"public","relation":"popular_science","id":"5564"},{"id":"26","status":"public","relation":"dissertation_contains"}]},"author":[{"full_name":"Steinrück, Magdalena","orcid":"0000-0003-1229-9719","id":"2C023F40-F248-11E8-B48F-1D18A9856A87","last_name":"Steinrück","first_name":"Magdalena"},{"last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C"}],"volume":6,"date_created":"2018-12-11T11:48:01Z","date_updated":"2024-03-28T23:30:28Z","article_number":"e25100","publist_id":"6990","file_date_updated":"2020-07-14T12:47:48Z","citation":{"mla":"Steinrück, Magdalena, and Calin C. Guet. “Complex Chromosomal Neighborhood Effects Determine the Adaptive Potential of a Gene under Selection.” ELife, vol. 6, e25100, eLife Sciences Publications, 2017, doi:10.7554/eLife.25100.","short":"M. Steinrück, C.C. Guet, ELife 6 (2017).","chicago":"Steinrück, Magdalena, and Calin C Guet. “Complex Chromosomal Neighborhood Effects Determine the Adaptive Potential of a Gene under Selection.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.25100.","ama":"Steinrück M, Guet CC. Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection. eLife. 2017;6. doi:10.7554/eLife.25100","ista":"Steinrück M, Guet CC. 2017. Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection. eLife. 6, e25100.","ieee":"M. Steinrück and C. C. Guet, “Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection,” eLife, vol. 6. eLife Sciences Publications, 2017.","apa":"Steinrück, M., & Guet, C. C. (2017). Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.25100"},"publication":"eLife","date_published":"2017-07-25T00:00:00Z","scopus_import":1,"has_accepted_license":"1","day":"25","_id":"704","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":" 6","status":"public","ddc":["576"],"title":"Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection","pubrep_id":"890","file":[{"access_level":"open_access","file_name":"IST-2017-890-v1+1_elife-25100-v1.pdf","creator":"system","file_size":2092088,"content_type":"application/pdf","file_id":"4975","relation":"main_file","checksum":"6b908b5db9f61f6820ebd7f8fa815571","date_created":"2018-12-12T10:12:54Z","date_updated":"2020-07-14T12:47:48Z"},{"file_id":"4976","relation":"main_file","checksum":"ca21530389b720243552678125fdba35","date_updated":"2020-07-14T12:47:48Z","date_created":"2018-12-12T10:12:55Z","access_level":"open_access","file_name":"IST-2017-890-v1+2_elife-25100-figures-v1.pdf","creator":"system","content_type":"application/pdf","file_size":3428681}],"oa_version":"Published Version","type":"journal_article","abstract":[{"text":"How the organization of genes on a chromosome shapes adaptation is essential for understanding evolutionary paths. Here, we investigate how adaptation to rapidly increasing levels of antibiotic depends on the chromosomal neighborhood of a drug-resistance gene inserted at different positions of the Escherichia coli chromosome. Using a dual-fluorescence reporter that allows us to distinguish gene amplifications from other up-mutations, we track in real-time adaptive changes in expression of the drug-resistance gene. We find that the relative contribution of several mutation types differs systematically between loci due to properties of neighboring genes: essentiality, expression, orientation, termination, and presence of duplicates. These properties determine rate and fitness effects of gene amplification, deletions, and mutations compromising transcriptional termination. Thus, the adaptive potential of a gene under selection is a system-property with a complex genetic basis that is specific for each chromosomal locus, and it can be inferred from detailed functional and genomic data.","lang":"eng"}]},{"ec_funded":1,"publist_id":"7004","file_date_updated":"2020-07-14T12:47:46Z","article_number":"e1005609","related_material":{"record":[{"id":"9849","status":"public","relation":"research_data"},{"relation":"research_data","status":"public","id":"9850"},{"status":"public","relation":"research_data","id":"9851"},{"status":"public","relation":"research_data","id":"9852"},{"id":"6263","status":"public","relation":"dissertation_contains"}]},"author":[{"full_name":"Lukacisinova, Marta","last_name":"Lukacisinova","first_name":"Marta","orcid":"0000-0002-2519-8004","id":"4342E402-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Novak, Sebastian","first_name":"Sebastian","last_name":"Novak","id":"461468AE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2519-824X"},{"full_name":"Paixao, Tiago","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2361-3953","first_name":"Tiago","last_name":"Paixao"}],"volume":13,"date_updated":"2024-03-28T23:30:28Z","date_created":"2018-12-11T11:47:58Z","year":"2017","publisher":"Public Library of Science","department":[{"_id":"ToBo"},{"_id":"NiBa"},{"_id":"CaGu"}],"publication_status":"published","publication_identifier":{"issn":["1553734X"]},"month":"07","doi":"10.1371/journal.pcbi.1005609","language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"project":[{"_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","grant_number":"618091","call_identifier":"FP7","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation"}],"quality_controlled":"1","issue":"7","abstract":[{"lang":"eng","text":"Mutator strains are expected to evolve when the availability and effect of beneficial mutations are high enough to counteract the disadvantage from deleterious mutations that will inevitably accumulate. As the population becomes more adapted to its environment, both availability and effect of beneficial mutations necessarily decrease and mutation rates are predicted to decrease. It has been shown that certain molecular mechanisms can lead to increased mutation rates when the organism finds itself in a stressful environment. While this may be a correlated response to other functions, it could also be an adaptive mechanism, raising mutation rates only when it is most advantageous. Here, we use a mathematical model to investigate the plausibility of the adaptive hypothesis. We show that such a mechanism can be mantained if the population is subjected to diverse stresses. By simulating various antibiotic treatment schemes, we find that combination treatments can reduce the effectiveness of second-order selection on stress-induced mutagenesis. We discuss the implications of our results to strategies of antibiotic therapy."}],"type":"journal_article","pubrep_id":"894","oa_version":"Published Version","file":[{"creator":"system","file_size":3775716,"content_type":"application/pdf","access_level":"open_access","file_name":"IST-2017-894-v1+1_journal.pcbi.1005609.pdf","checksum":"9143c290fa6458ed2563bff4b295554a","date_created":"2018-12-12T10:15:01Z","date_updated":"2020-07-14T12:47:46Z","file_id":"5117","relation":"main_file"}],"_id":"696","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":" 13","title":"Stress induced mutagenesis: Stress diversity facilitates the persistence of mutator genes","ddc":["576"],"status":"public","has_accepted_license":"1","day":"18","scopus_import":1,"date_published":"2017-07-18T00:00:00Z","citation":{"apa":"Lukacisinova, M., Novak, S., & Paixao, T. (2017). Stress induced mutagenesis: Stress diversity facilitates the persistence of mutator genes. PLoS Computational Biology. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1005609","ieee":"M. Lukacisinova, S. Novak, and T. Paixao, “Stress induced mutagenesis: Stress diversity facilitates the persistence of mutator genes,” PLoS Computational Biology, vol. 13, no. 7. Public Library of Science, 2017.","ista":"Lukacisinova M, Novak S, Paixao T. 2017. Stress induced mutagenesis: Stress diversity facilitates the persistence of mutator genes. PLoS Computational Biology. 13(7), e1005609.","ama":"Lukacisinova M, Novak S, Paixao T. Stress induced mutagenesis: Stress diversity facilitates the persistence of mutator genes. PLoS Computational Biology. 2017;13(7). doi:10.1371/journal.pcbi.1005609","chicago":"Lukacisinova, Marta, Sebastian Novak, and Tiago Paixao. “Stress Induced Mutagenesis: Stress Diversity Facilitates the Persistence of Mutator Genes.” PLoS Computational Biology. Public Library of Science, 2017. https://doi.org/10.1371/journal.pcbi.1005609.","short":"M. Lukacisinova, S. Novak, T. Paixao, PLoS Computational Biology 13 (2017).","mla":"Lukacisinova, Marta, et al. “Stress Induced Mutagenesis: Stress Diversity Facilitates the Persistence of Mutator Genes.” PLoS Computational Biology, vol. 13, no. 7, e1005609, Public Library of Science, 2017, doi:10.1371/journal.pcbi.1005609."},"publication":"PLoS Computational Biology","article_type":"original"},{"month":"10","publication_identifier":{"issn":["15345807"]},"doi":"10.1016/j.devcel.2017.09.014","language":[{"iso":"eng"}],"external_id":{"isi":["000413443700011"]},"quality_controlled":"1","isi":1,"project":[{"_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734","call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme"},{"grant_number":"I2058","_id":"252DD2A6-B435-11E9-9278-68D0E5697425","name":"Cell segregation in gastrulation: the role of cell fate specification","call_identifier":"FWF"}],"ec_funded":1,"publist_id":"6934","author":[{"full_name":"Barone, Vanessa","first_name":"Vanessa","last_name":"Barone","id":"419EECCC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2676-3367"},{"full_name":"Lang, Moritz","id":"29E0800A-F248-11E8-B48F-1D18A9856A87","last_name":"Lang","first_name":"Moritz"},{"last_name":"Krens","first_name":"Gabriel","orcid":"0000-0003-4761-5996","id":"2B819732-F248-11E8-B48F-1D18A9856A87","full_name":"Krens, Gabriel"},{"first_name":"Saurabh","last_name":"Pradhan","full_name":"Pradhan, Saurabh"},{"full_name":"Shamipour, Shayan","id":"40B34FE2-F248-11E8-B48F-1D18A9856A87","last_name":"Shamipour","first_name":"Shayan"},{"full_name":"Sako, Keisuke","last_name":"Sako","first_name":"Keisuke","orcid":"0000-0002-6453-8075","id":"3BED66BE-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Sikora, Mateusz K","first_name":"Mateusz K","last_name":"Sikora","id":"2F74BCDE-F248-11E8-B48F-1D18A9856A87"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet","full_name":"Guet, Calin C"},{"last_name":"Heisenberg","first_name":"Carl-Philipp J","orcid":"0000-0002-0912-4566","id":"39427864-F248-11E8-B48F-1D18A9856A87","full_name":"Heisenberg, Carl-Philipp J"}],"related_material":{"record":[{"id":"961","status":"public","relation":"dissertation_contains"},{"status":"public","relation":"dissertation_contains","id":"8350"}]},"date_created":"2018-12-11T11:48:13Z","date_updated":"2024-03-28T23:30:39Z","volume":43,"year":"2017","publication_status":"published","department":[{"_id":"CaHe"},{"_id":"CaGu"},{"_id":"GaTk"}],"publisher":"Cell Press","day":"23","article_processing_charge":"No","scopus_import":"1","date_published":"2017-10-23T00:00:00Z","publication":"Developmental Cell","citation":{"apa":"Barone, V., Lang, M., Krens, G., Pradhan, S., Shamipour, S., Sako, K., … Heisenberg, C.-P. J. (2017). An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate. Developmental Cell. Cell Press. https://doi.org/10.1016/j.devcel.2017.09.014","ieee":"V. Barone et al., “An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate,” Developmental Cell, vol. 43, no. 2. Cell Press, pp. 198–211, 2017.","ista":"Barone V, Lang M, Krens G, Pradhan S, Shamipour S, Sako K, Sikora MK, Guet CC, Heisenberg C-PJ. 2017. An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate. Developmental Cell. 43(2), 198–211.","ama":"Barone V, Lang M, Krens G, et al. An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate. Developmental Cell. 2017;43(2):198-211. doi:10.1016/j.devcel.2017.09.014","chicago":"Barone, Vanessa, Moritz Lang, Gabriel Krens, Saurabh Pradhan, Shayan Shamipour, Keisuke Sako, Mateusz K Sikora, Calin C Guet, and Carl-Philipp J Heisenberg. “An Effective Feedback Loop between Cell-Cell Contact Duration and Morphogen Signaling Determines Cell Fate.” Developmental Cell. Cell Press, 2017. https://doi.org/10.1016/j.devcel.2017.09.014.","short":"V. Barone, M. Lang, G. Krens, S. Pradhan, S. Shamipour, K. Sako, M.K. Sikora, C.C. Guet, C.-P.J. Heisenberg, Developmental Cell 43 (2017) 198–211.","mla":"Barone, Vanessa, et al. “An Effective Feedback Loop between Cell-Cell Contact Duration and Morphogen Signaling Determines Cell Fate.” Developmental Cell, vol. 43, no. 2, Cell Press, 2017, pp. 198–211, doi:10.1016/j.devcel.2017.09.014."},"page":"198 - 211","abstract":[{"lang":"eng","text":"Cell-cell contact formation constitutes an essential step in evolution, leading to the differentiation of specialized cell types. However, remarkably little is known about whether and how the interplay between contact formation and fate specification affects development. Here, we identify a positive feedback loop between cell-cell contact duration, morphogen signaling, and mesendoderm cell-fate specification during zebrafish gastrulation. We show that long-lasting cell-cell contacts enhance the competence of prechordal plate (ppl) progenitor cells to respond to Nodal signaling, required for ppl cell-fate specification. We further show that Nodal signaling promotes ppl cell-cell contact duration, generating a positive feedback loop between ppl cell-cell contact duration and cell-fate specification. Finally, by combining mathematical modeling and experimentation, we show that this feedback determines whether anterior axial mesendoderm cells become ppl or, instead, turn into endoderm. Thus, the interdependent activities of cell-cell signaling and contact formation control fate diversification within the developing embryo."}],"issue":"2","type":"journal_article","oa_version":"None","_id":"735","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","title":"An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate","status":"public","intvolume":" 43"},{"author":[{"first_name":"Robert","last_name":"Gnügge","full_name":"Gnügge, Robert"},{"first_name":"Lekshmi","last_name":"Dharmarajan","full_name":"Dharmarajan, Lekshmi"},{"full_name":"Lang, Moritz","last_name":"Lang","first_name":"Moritz","id":"29E0800A-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Stelling, Jörg","last_name":"Stelling","first_name":"Jörg"}],"oa_version":"None","volume":5,"date_updated":"2021-01-12T06:47:37Z","date_created":"2018-12-11T11:49:40Z","acknowledgement":"We thank Julio Polaina (Instituto de Agroqu ı ́ mica y Tecnolog ı ́ a de Alimentos, C.S.I.C., Paterna, Spain) for the gift of plasmid pMR4, Gregor W. Schmidt for provision of and support with the micro fl uidic device, Markus Du ̈ rr for the cell tracking R script, and Lukas Widmer for the script for MEIGO using “ parfor ” in MATLAB. We acknowledge the members of the Stelling group for discussions, comments, and support.","_id":"1008","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","year":"2016","publisher":"American Chemical Society","department":[{"_id":"CaGu"}],"intvolume":" 5","status":"public","title":"An orthogonal permease–inducer–repressor feedback loop shows bistability","publication_status":"published","issue":"10","publist_id":"6390","abstract":[{"text":"Feedback loops in biological networks, among others, enable differentiation and cell cycle progression, and increase robustness in signal transduction. In natural networks, feedback loops are often complex and intertwined, making it challenging to identify which loops are mainly responsible for an observed behavior. However, minimal synthetic replicas could allow for such identification. Here, we engineered a synthetic permease-inducer-repressor system in Saccharomyces cerevisiae to analyze if a transport-mediated positive feedback loop could be a core mechanism for the switch-like behavior in the regulation of metabolic gene networks such as the S. cerevisiae GAL system or the Escherichia coli lac operon. We characterized the synthetic circuit using deterministic and stochastic mathematical models. Similar to its natural counterparts, our synthetic system shows bistable and hysteretic behavior, and the inducer concentration range for bistability as well as the switching rates between the two stable states depend on the repressor concentration. Our results indicate that a generic permease–inducer–repressor circuit with a single feedback loop is sufficient to explain the experimentally observed bistable behavior of the natural systems. We anticipate that the approach of reimplementing natural systems with orthogonal parts to identify crucial network components is applicable to other natural systems such as signaling pathways.","lang":"eng"}],"type":"journal_article","date_published":"2016-05-05T00:00:00Z","doi":"10.1021/acssynbio.6b00013","language":[{"iso":"eng"}],"citation":{"short":"R. Gnügge, L. Dharmarajan, M. Lang, J. Stelling, ACS Synthetic Biology 5 (2016) 1098–1107.","mla":"Gnügge, Robert, et al. “An Orthogonal Permease–Inducer–Repressor Feedback Loop Shows Bistability.” ACS Synthetic Biology, vol. 5, no. 10, American Chemical Society, 2016, pp. 1098–107, doi:10.1021/acssynbio.6b00013.","chicago":"Gnügge, Robert, Lekshmi Dharmarajan, Moritz Lang, and Jörg Stelling. “An Orthogonal Permease–Inducer–Repressor Feedback Loop Shows Bistability.” ACS Synthetic Biology. American Chemical Society, 2016. https://doi.org/10.1021/acssynbio.6b00013.","ama":"Gnügge R, Dharmarajan L, Lang M, Stelling J. An orthogonal permease–inducer–repressor feedback loop shows bistability. ACS Synthetic Biology. 2016;5(10):1098-1107. doi:10.1021/acssynbio.6b00013","apa":"Gnügge, R., Dharmarajan, L., Lang, M., & Stelling, J. (2016). An orthogonal permease–inducer–repressor feedback loop shows bistability. ACS Synthetic Biology. American Chemical Society. https://doi.org/10.1021/acssynbio.6b00013","ieee":"R. Gnügge, L. Dharmarajan, M. Lang, and J. Stelling, “An orthogonal permease–inducer–repressor feedback loop shows bistability,” ACS Synthetic Biology, vol. 5, no. 10. American Chemical Society, pp. 1098–1107, 2016.","ista":"Gnügge R, Dharmarajan L, Lang M, Stelling J. 2016. An orthogonal permease–inducer–repressor feedback loop shows bistability. ACS Synthetic Biology. 5(10), 1098–1107."},"publication":"ACS Synthetic Biology","page":"1098 - 1107","quality_controlled":"1","month":"05","day":"05"},{"type":"journal_article","abstract":[{"lang":"eng","text":"The increasing complexity of dynamic models in systems and synthetic biology poses computational challenges especially for the identification of model parameters. While modularization of the corresponding optimization problems could help reduce the “curse of dimensionality,” abundant feedback and crosstalk mechanisms prohibit a simple decomposition of most biomolecular networks into subnetworks, or modules. Drawing on ideas from network modularization and multiple-shooting optimization, we present here a modular parameter identification approach that explicitly allows for such interdependencies. Interfaces between our modules are given by the experimentally measured molecular species. This definition allows deriving good (initial) estimates for the inter-module communication directly from the experimental data. Given these estimates, the states and parameter sensitivities of different modules can be integrated independently. To achieve consistency between modules, we iteratively adjust the estimates for inter-module communication while optimizing the parameters. After convergence to an optimal parameter set---but not during earlier iterations---the intermodule communication as well as the individual modules\\' state dynamics agree with the dynamics of the nonmodularized network. Our modular parameter identification approach allows for easy parallelization; it can reduce the computational complexity for larger networks and decrease the probability to converge to suboptimal local minima. We demonstrate the algorithm\\'s performance in parameter estimation for two biomolecular networks, a synthetic genetic oscillator and a mammalian signaling pathway."}],"issue":"6","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","_id":"1170","status":"public","title":"Modular parameter identification of biomolecular networks","ddc":["003","518","570","621"],"intvolume":" 38","pubrep_id":"811","file":[{"relation":"main_file","file_id":"5095","date_updated":"2020-07-14T12:44:37Z","date_created":"2018-12-12T10:14:41Z","checksum":"781bc3ffd30b2dd65b7727c5a285fc78","file_name":"IST-2017-811-v1+1_modular_parameter_identification.pdf","access_level":"local","file_size":871964,"content_type":"application/pdf","creator":"system"}],"oa_version":"Submitted Version","scopus_import":1,"day":"15","has_accepted_license":"1","publication":"SIAM Journal on Scientific Computing","citation":{"ieee":"M. Lang and J. Stelling, “Modular parameter identification of biomolecular networks,” SIAM Journal on Scientific Computing, vol. 38, no. 6. Society for Industrial and Applied Mathematics , pp. B988–B1008, 2016.","apa":"Lang, M., & Stelling, J. (2016). Modular parameter identification of biomolecular networks. SIAM Journal on Scientific Computing. Society for Industrial and Applied Mathematics . https://doi.org/10.1137/15M103306X","ista":"Lang M, Stelling J. 2016. Modular parameter identification of biomolecular networks. SIAM Journal on Scientific Computing. 38(6), B988–B1008.","ama":"Lang M, Stelling J. Modular parameter identification of biomolecular networks. SIAM Journal on Scientific Computing. 2016;38(6):B988-B1008. doi:10.1137/15M103306X","chicago":"Lang, Moritz, and Jörg Stelling. “Modular Parameter Identification of Biomolecular Networks.” SIAM Journal on Scientific Computing. Society for Industrial and Applied Mathematics , 2016. https://doi.org/10.1137/15M103306X.","short":"M. Lang, J. Stelling, SIAM Journal on Scientific Computing 38 (2016) B988–B1008.","mla":"Lang, Moritz, and Jörg Stelling. “Modular Parameter Identification of Biomolecular Networks.” SIAM Journal on Scientific Computing, vol. 38, no. 6, Society for Industrial and Applied Mathematics , 2016, pp. B988–1008, doi:10.1137/15M103306X."},"page":"B988 - B1008","date_published":"2016-11-15T00:00:00Z","file_date_updated":"2020-07-14T12:44:37Z","publist_id":"6186","year":"2016","publication_status":"published","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publisher":"Society for Industrial and Applied Mathematics ","author":[{"first_name":"Moritz","last_name":"Lang","id":"29E0800A-F248-11E8-B48F-1D18A9856A87","full_name":"Lang, Moritz"},{"full_name":"Stelling, Jörg","last_name":"Stelling","first_name":"Jörg"}],"date_updated":"2021-01-12T06:48:49Z","date_created":"2018-12-11T11:50:31Z","volume":38,"month":"11","quality_controlled":"1","doi":"10.1137/15M103306X","language":[{"iso":"eng"}]},{"publisher":"AIAA","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"title":"Fuselage boundary layer ingestion propulsion applied to a thin haul commuter aircraft for optimal efficiency","status":"public","publication_status":"published","year":"2016","_id":"1220","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","oa_version":"Preprint","date_updated":"2023-02-21T10:17:50Z","date_created":"2018-12-11T11:50:47Z","author":[{"full_name":"Mikić, Gregor","first_name":"Gregor","last_name":"Mikić"},{"full_name":"Stoll, Alex","last_name":"Stoll","first_name":"Alex"},{"first_name":"Joe","last_name":"Bevirt","full_name":"Bevirt, Joe"},{"first_name":"Rok","last_name":"Grah","id":"483E70DE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2539-3560","full_name":"Grah, Rok"},{"last_name":"Moore","first_name":"Mark","full_name":"Moore, Mark"}],"type":"conference","publist_id":"6114","abstract":[{"lang":"eng","text":"Theoretical and numerical aspects of aerodynamic efficiency of propulsion systems coupled to the boundary layer of a fuselage are studied. We discuss the effects of local flow fields, which are affected both by conservative flow acceleration as well as total pressure losses, on the efficiency of boundary layer immersed propulsion devices. We introduce the concept of a boundary layer retardation turbine that helps reduce skin friction over the fuselage. We numerically investigate efficiency gains offered by boundary layer and wake interacting devices. We discuss the results in terms of a total energy consumption framework and show that efficiency gains of any device depend on all the other elements of the propulsion system."}],"page":"1 - 19","quality_controlled":"1","oa":1,"citation":{"ieee":"G. Mikić, A. Stoll, J. Bevirt, R. Grah, and M. Moore, “Fuselage boundary layer ingestion propulsion applied to a thin haul commuter aircraft for optimal efficiency,” presented at the AIAA: Aviation Technology, Integration, and Operations Conference, Washington, D.C., USA, 2016, pp. 1–19.","apa":"Mikić, G., Stoll, A., Bevirt, J., Grah, R., & Moore, M. (2016). Fuselage boundary layer ingestion propulsion applied to a thin haul commuter aircraft for optimal efficiency (pp. 1–19). Presented at the AIAA: Aviation Technology, Integration, and Operations Conference, Washington, D.C., USA: AIAA. https://doi.org/10.2514/6.2016-3764","ista":"Mikić G, Stoll A, Bevirt J, Grah R, Moore M. 2016. Fuselage boundary layer ingestion propulsion applied to a thin haul commuter aircraft for optimal efficiency. AIAA: Aviation Technology, Integration, and Operations Conference, 1–19.","ama":"Mikić G, Stoll A, Bevirt J, Grah R, Moore M. Fuselage boundary layer ingestion propulsion applied to a thin haul commuter aircraft for optimal efficiency. In: AIAA; 2016:1-19. doi:10.2514/6.2016-3764","chicago":"Mikić, Gregor, Alex Stoll, Joe Bevirt, Rok Grah, and Mark Moore. “Fuselage Boundary Layer Ingestion Propulsion Applied to a Thin Haul Commuter Aircraft for Optimal Efficiency,” 1–19. AIAA, 2016. https://doi.org/10.2514/6.2016-3764.","short":"G. Mikić, A. Stoll, J. Bevirt, R. Grah, M. Moore, in:, AIAA, 2016, pp. 1–19.","mla":"Mikić, Gregor, et al. Fuselage Boundary Layer Ingestion Propulsion Applied to a Thin Haul Commuter Aircraft for Optimal Efficiency. AIAA, 2016, pp. 1–19, doi:10.2514/6.2016-3764."},"main_file_link":[{"url":"https://ntrs.nasa.gov/search.jsp?R=20160010167&hterms=Fuselage+boundary+layer+ingestion+propulsion+applied+thin+haul+commuter+aircraft+optimal+efficiency&qs=N%3D0%26Ntk%3DAll%26Ntt%3DFuselage%2520boundary%2520layer%2520ingestion%2520propulsion%2520applied%2520to%2520a%2520thin%2520haul%2520commuter%2520aircraft%2520for%2520optimal%2520efficiency%26Ntx%3Dmode%2520matchallpartial%26Nm%3D123%7CCollection%7CNASA%2520STI%7C%7C17%7CCollection%7CNACA","open_access":"1"}],"language":[{"iso":"eng"}],"date_published":"2016-06-01T00:00:00Z","doi":"10.2514/6.2016-3764","conference":{"start_date":"2016-06-13","location":"Washington, D.C., USA","end_date":"2016-06-17","name":"AIAA: Aviation Technology, Integration, and Operations Conference"},"scopus_import":1,"day":"01","month":"06"},{"day":"01","scopus_import":1,"date_published":"2016-11-01T00:00:00Z","page":"902 - 904","citation":{"ama":"Stone L, Baym M, Lieberman T, Chait RP, Clardy J, Kishony R. Compounds that select against the tetracycline-resistance efflux pump. Nature Chemical Biology. 2016;12(11):902-904. doi:10.1038/nchembio.2176","ista":"Stone L, Baym M, Lieberman T, Chait RP, Clardy J, Kishony R. 2016. Compounds that select against the tetracycline-resistance efflux pump. Nature Chemical Biology. 12(11), 902–904.","apa":"Stone, L., Baym, M., Lieberman, T., Chait, R. P., Clardy, J., & Kishony, R. (2016). Compounds that select against the tetracycline-resistance efflux pump. Nature Chemical Biology. Nature Publishing Group. https://doi.org/10.1038/nchembio.2176","ieee":"L. Stone, M. Baym, T. Lieberman, R. P. Chait, J. Clardy, and R. Kishony, “Compounds that select against the tetracycline-resistance efflux pump,” Nature Chemical Biology, vol. 12, no. 11. Nature Publishing Group, pp. 902–904, 2016.","mla":"Stone, Laura, et al. “Compounds That Select against the Tetracycline-Resistance Efflux Pump.” Nature Chemical Biology, vol. 12, no. 11, Nature Publishing Group, 2016, pp. 902–04, doi:10.1038/nchembio.2176.","short":"L. Stone, M. Baym, T. Lieberman, R.P. Chait, J. Clardy, R. Kishony, Nature Chemical Biology 12 (2016) 902–904.","chicago":"Stone, Laura, Michael Baym, Tami Lieberman, Remy P Chait, Jon Clardy, and Roy Kishony. “Compounds That Select against the Tetracycline-Resistance Efflux Pump.” Nature Chemical Biology. Nature Publishing Group, 2016. https://doi.org/10.1038/nchembio.2176."},"publication":"Nature Chemical Biology","issue":"11","abstract":[{"lang":"eng","text":"We developed a competition-based screening strategy to identify compounds that invert the selective advantage of antibiotic resistance. Using our assay, we screened over 19,000 compounds for the ability to select against the TetA tetracycline-resistance efflux pump in Escherichia coli and identified two hits, β-thujaplicin and disulfiram. Treating a tetracycline-resistant population with β-thujaplicin selects for loss of the resistance gene, enabling an effective second-phase treatment with doxycycline."}],"type":"journal_article","oa_version":"Preprint","intvolume":" 12","status":"public","title":"Compounds that select against the tetracycline-resistance efflux pump","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","_id":"1290","month":"11","language":[{"iso":"eng"}],"doi":"10.1038/nchembio.2176","quality_controlled":"1","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5069154/","open_access":"1"}],"oa":1,"publist_id":"6026","volume":12,"date_updated":"2021-01-12T06:49:39Z","date_created":"2018-12-11T11:51:10Z","author":[{"full_name":"Stone, Laura","first_name":"Laura","last_name":"Stone"},{"full_name":"Baym, Michael","first_name":"Michael","last_name":"Baym"},{"first_name":"Tami","last_name":"Lieberman","full_name":"Lieberman, Tami"},{"last_name":"Chait","first_name":"Remy P","orcid":"0000-0003-0876-3187","id":"3464AE84-F248-11E8-B48F-1D18A9856A87","full_name":"Chait, Remy P"},{"full_name":"Clardy, Jon","last_name":"Clardy","first_name":"Jon"},{"first_name":"Roy","last_name":"Kishony","full_name":"Kishony, Roy"}],"department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publisher":"Nature Publishing Group","publication_status":"published","acknowledgement":"This work was supported in part by National Institute of Allergy and Infectious Diseases grant U54 AI057159, US National Institutes of Health grants R01 GM081617 (to R.K.) and GM086258 (to J.C.), European Research Council FP7 ERC grant 281891 (to R.K.) and a National Science Foundation Graduate Fellowship (to L.K.S.).\r\n","year":"2016"},{"file_date_updated":"2020-07-14T12:44:43Z","publist_id":"5950","ec_funded":1,"article_number":"7526722","date_updated":"2021-01-12T06:49:51Z","date_created":"2018-12-11T11:51:21Z","volume":"2016-July","author":[{"id":"29E0800A-F248-11E8-B48F-1D18A9856A87","last_name":"Lang","first_name":"Moritz","full_name":"Lang, Moritz"},{"full_name":"Sontag, Eduardo","first_name":"Eduardo","last_name":"Sontag"}],"publication_status":"published","publisher":"IEEE","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"year":"2016","acknowledgement":"The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement n° [291734]. Work supported in part by grants AFOSR FA9550-14-1-0060 and NIH 1R01GM100473.","month":"07","language":[{"iso":"eng"}],"conference":{"name":"ACC: American Control Conference","location":"Boston, MA, USA","start_date":"2016-07-06","end_date":"2016-07-08"},"doi":"10.1109/ACC.2016.7526722","quality_controlled":"1","project":[{"grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425","name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7"}],"abstract":[{"text":"In recent years, several biomolecular systems have been shown to be scale-invariant (SI), i.e. to show the same output dynamics when exposed to geometrically scaled input signals (u → pu, p > 0) after pre-adaptation to accordingly scaled constant inputs. In this article, we show that SI systems-as well as systems invariant with respect to other input transformations-can realize nonlinear differential operators: when excited by inputs obeying functional forms characteristic for a given class of invariant systems, the systems' outputs converge to constant values directly quantifying the speed of the input.","lang":"eng"}],"type":"conference","file":[{"creator":"system","content_type":"application/pdf","file_size":539166,"access_level":"local","file_name":"IST-2017-810-v1+1_root.pdf","checksum":"7219432b43defc62a0d45f48d4ce6a19","date_updated":"2020-07-14T12:44:43Z","date_created":"2018-12-12T10:16:17Z","file_id":"5203","relation":"main_file"}],"oa_version":"Preprint","pubrep_id":"810","status":"public","title":"Scale-invariant systems realize nonlinear differential operators","ddc":["003","621"],"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","_id":"1320","day":"28","has_accepted_license":"1","scopus_import":1,"date_published":"2016-07-28T00:00:00Z","citation":{"mla":"Lang, Moritz, and Eduardo Sontag. Scale-Invariant Systems Realize Nonlinear Differential Operators. Vol. 2016–July, 7526722, IEEE, 2016, doi:10.1109/ACC.2016.7526722.","short":"M. Lang, E. Sontag, in:, IEEE, 2016.","chicago":"Lang, Moritz, and Eduardo Sontag. “Scale-Invariant Systems Realize Nonlinear Differential Operators,” Vol. 2016–July. IEEE, 2016. https://doi.org/10.1109/ACC.2016.7526722.","ama":"Lang M, Sontag E. Scale-invariant systems realize nonlinear differential operators. In: Vol 2016-July. IEEE; 2016. doi:10.1109/ACC.2016.7526722","ista":"Lang M, Sontag E. 2016. Scale-invariant systems realize nonlinear differential operators. ACC: American Control Conference vol. 2016–July, 7526722.","apa":"Lang, M., & Sontag, E. (2016). Scale-invariant systems realize nonlinear differential operators (Vol. 2016–July). Presented at the ACC: American Control Conference, Boston, MA, USA: IEEE. https://doi.org/10.1109/ACC.2016.7526722","ieee":"M. Lang and E. Sontag, “Scale-invariant systems realize nonlinear differential operators,” presented at the ACC: American Control Conference, Boston, MA, USA, 2016, vol. 2016–July."}},{"date_updated":"2021-01-12T06:49:57Z","date_created":"2018-12-11T11:51:25Z","volume":7,"author":[{"first_name":"Remy P","last_name":"Chait","id":"3464AE84-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0876-3187","full_name":"Chait, Remy P"},{"last_name":"Palmer","first_name":"Adam","full_name":"Palmer, Adam"},{"first_name":"Idan","last_name":"Yelin","full_name":"Yelin, Idan"},{"full_name":"Kishony, Roy","last_name":"Kishony","first_name":"Roy"}],"publication_status":"published","publisher":"Nature Publishing Group","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"acknowledgement":"This work was partially supported by US National Institutes of Health grant R01-GM081617, Israeli Centers of Research Excellence I-CORE Program ISF Grant No. 152/11, and the European Research Council FP7 ERC Grant 281891.","year":"2016","file_date_updated":"2020-07-14T12:44:44Z","publist_id":"5936","article_number":"10333","language":[{"iso":"eng"}],"doi":"10.1038/ncomms10333","quality_controlled":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"month":"01","oa_version":"Published Version","file":[{"date_updated":"2020-07-14T12:44:44Z","date_created":"2018-12-12T10:13:52Z","checksum":"ef147bcbb8bd37e9079cf3ce06f5815d","file_id":"5039","relation":"main_file","creator":"system","file_size":1844107,"content_type":"application/pdf","file_name":"IST-2016-662-v1+1_ncomms10333.pdf","access_level":"open_access"}],"pubrep_id":"662","ddc":["570","579"],"title":"Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments","status":"public","intvolume":" 7","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","_id":"1332","abstract":[{"lang":"eng","text":"Antibiotic-sensitive and -resistant bacteria coexist in natural environments with low, if detectable, antibiotic concentrations. Except possibly around localized antibiotic sources, where resistance can provide a strong advantage, bacterial fitness is dominated by stresses unaffected by resistance to the antibiotic. How do such mixed and heterogeneous conditions influence the selective advantage or disadvantage of antibiotic resistance? Here we find that sub-inhibitory levels of tetracyclines potentiate selection for or against tetracycline resistance around localized sources of almost any toxin or stress. Furthermore, certain stresses generate alternating rings of selection for and against resistance around a localized source of the antibiotic. In these conditions, localized antibiotic sources, even at high strengths, can actually produce a net selection against resistance to the antibiotic. Our results show that interactions between the effects of an antibiotic and other stresses in inhomogeneous environments can generate pervasive, complex patterns of selection both for and against antibiotic resistance."}],"type":"journal_article","date_published":"2016-01-20T00:00:00Z","publication":"Nature Communications","citation":{"chicago":"Chait, Remy P, Adam Palmer, Idan Yelin, and Roy Kishony. “Pervasive Selection for and against Antibiotic Resistance in Inhomogeneous Multistress Environments.” Nature Communications. Nature Publishing Group, 2016. https://doi.org/10.1038/ncomms10333.","short":"R.P. Chait, A. Palmer, I. Yelin, R. Kishony, Nature Communications 7 (2016).","mla":"Chait, Remy P., et al. “Pervasive Selection for and against Antibiotic Resistance in Inhomogeneous Multistress Environments.” Nature Communications, vol. 7, 10333, Nature Publishing Group, 2016, doi:10.1038/ncomms10333.","apa":"Chait, R. P., Palmer, A., Yelin, I., & Kishony, R. (2016). Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments. Nature Communications. Nature Publishing Group. https://doi.org/10.1038/ncomms10333","ieee":"R. P. Chait, A. Palmer, I. Yelin, and R. Kishony, “Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments,” Nature Communications, vol. 7. Nature Publishing Group, 2016.","ista":"Chait RP, Palmer A, Yelin I, Kishony R. 2016. Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments. Nature Communications. 7, 10333.","ama":"Chait RP, Palmer A, Yelin I, Kishony R. Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments. Nature Communications. 2016;7. doi:10.1038/ncomms10333"},"day":"20","has_accepted_license":"1","scopus_import":1},{"abstract":[{"text":"A key aspect of bacterial survival is the ability to evolve while migrating across spatially varying environmental challenges. Laboratory experiments, however, often study evolution in well-mixed systems. Here, we introduce an experimental device, the microbial evolution and growth arena (MEGA)-plate, in which bacteria spread and evolved on a large antibiotic landscape (120 × 60 centimeters) that allowed visual observation of mutation and selection in a migrating bacterial front.While resistance increased consistently, multiple coexisting lineages diversified both phenotypically and genotypically. Analyzing mutants at and behind the propagating front,we found that evolution is not always led by the most resistant mutants; highly resistant mutants may be trapped behindmore sensitive lineages.TheMEGA-plate provides a versatile platformfor studying microbial adaption and directly visualizing evolutionary dynamics.","lang":"eng"}],"issue":"6304","publist_id":"5911","type":"journal_article","author":[{"last_name":"Baym","first_name":"Michael","full_name":"Baym, Michael"},{"last_name":"Lieberman","first_name":"Tami","full_name":"Lieberman, Tami"},{"full_name":"Kelsic, Eric","last_name":"Kelsic","first_name":"Eric"},{"last_name":"Chait","first_name":"Remy P","orcid":"0000-0003-0876-3187","id":"3464AE84-F248-11E8-B48F-1D18A9856A87","full_name":"Chait, Remy P"},{"full_name":"Gross, Rotem","last_name":"Gross","first_name":"Rotem"},{"full_name":"Yelin, Idan","first_name":"Idan","last_name":"Yelin"},{"full_name":"Kishony, Roy","first_name":"Roy","last_name":"Kishony"}],"date_created":"2018-12-11T11:51:29Z","date_updated":"2021-01-12T06:50:01Z","oa_version":"Preprint","volume":353,"_id":"1342","year":"2016","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","status":"public","title":"Spatiotemporal microbial evolution on antibiotic landscapes","publication_status":"published","publisher":"American Association for the Advancement of Science","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"intvolume":" 353","day":"09","month":"09","scopus_import":1,"date_published":"2016-09-09T00:00:00Z","doi":"10.1126/science.aag0822","language":[{"iso":"eng"}],"publication":"Science","main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5534434/"}],"oa":1,"citation":{"ama":"Baym M, Lieberman T, Kelsic E, et al. Spatiotemporal microbial evolution on antibiotic landscapes. Science. 2016;353(6304):1147-1151. doi:10.1126/science.aag0822","ista":"Baym M, Lieberman T, Kelsic E, Chait RP, Gross R, Yelin I, Kishony R. 2016. Spatiotemporal microbial evolution on antibiotic landscapes. Science. 353(6304), 1147–1151.","ieee":"M. Baym et al., “Spatiotemporal microbial evolution on antibiotic landscapes,” Science, vol. 353, no. 6304. American Association for the Advancement of Science, pp. 1147–1151, 2016.","apa":"Baym, M., Lieberman, T., Kelsic, E., Chait, R. P., Gross, R., Yelin, I., & Kishony, R. (2016). Spatiotemporal microbial evolution on antibiotic landscapes. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.aag0822","mla":"Baym, Michael, et al. “Spatiotemporal Microbial Evolution on Antibiotic Landscapes.” Science, vol. 353, no. 6304, American Association for the Advancement of Science, 2016, pp. 1147–51, doi:10.1126/science.aag0822.","short":"M. Baym, T. Lieberman, E. Kelsic, R.P. Chait, R. Gross, I. Yelin, R. Kishony, Science 353 (2016) 1147–1151.","chicago":"Baym, Michael, Tami Lieberman, Eric Kelsic, Remy P Chait, Rotem Gross, Idan Yelin, and Roy Kishony. “Spatiotemporal Microbial Evolution on Antibiotic Landscapes.” Science. American Association for the Advancement of Science, 2016. https://doi.org/10.1126/science.aag0822."},"quality_controlled":"1","page":"1147 - 1151"},{"month":"07","project":[{"_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","grant_number":"618091","call_identifier":"FP7","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation"}],"quality_controlled":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"language":[{"iso":"eng"}],"doi":"10.1145/2908812.2908909","conference":{"start_date":"2016-07-20","location":"Denver, CO, USA","end_date":"2016-07-24","name":"GECCO: Genetic and evolutionary computation conference"},"ec_funded":1,"publist_id":"5900","file_date_updated":"2020-07-14T12:44:45Z","department":[{"_id":"NiBa"},{"_id":"CaGu"}],"publisher":"ACM","publication_status":"published","year":"2016","date_updated":"2021-01-12T06:50:03Z","date_created":"2018-12-11T11:51:31Z","author":[{"last_name":"Oliveto","first_name":"Pietro","full_name":"Oliveto, Pietro"},{"full_name":"Paixao, Tiago","last_name":"Paixao","first_name":"Tiago","orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Heredia, Jorge","first_name":"Jorge","last_name":"Heredia"},{"first_name":"Dirk","last_name":"Sudholt","full_name":"Sudholt, Dirk"},{"last_name":"Trubenova","first_name":"Barbora","orcid":"0000-0002-6873-2967","id":"42302D54-F248-11E8-B48F-1D18A9856A87","full_name":"Trubenova, Barbora"}],"scopus_import":1,"has_accepted_license":"1","day":"20","page":"1163 - 1170","citation":{"ama":"Oliveto P, Paixao T, Heredia J, Sudholt D, Trubenova B. When non-elitism outperforms elitism for crossing fitness valleys. In: Proceedings of the Genetic and Evolutionary Computation Conference 2016 . ACM; 2016:1163-1170. doi:10.1145/2908812.2908909","ieee":"P. Oliveto, T. Paixao, J. Heredia, D. Sudholt, and B. Trubenova, “When non-elitism outperforms elitism for crossing fitness valleys,” in Proceedings of the Genetic and Evolutionary Computation Conference 2016 , Denver, CO, USA, 2016, pp. 1163–1170.","apa":"Oliveto, P., Paixao, T., Heredia, J., Sudholt, D., & Trubenova, B. (2016). When non-elitism outperforms elitism for crossing fitness valleys. In Proceedings of the Genetic and Evolutionary Computation Conference 2016 (pp. 1163–1170). Denver, CO, USA: ACM. https://doi.org/10.1145/2908812.2908909","ista":"Oliveto P, Paixao T, Heredia J, Sudholt D, Trubenova B. 2016. When non-elitism outperforms elitism for crossing fitness valleys. Proceedings of the Genetic and Evolutionary Computation Conference 2016 . GECCO: Genetic and evolutionary computation conference, 1163–1170.","short":"P. Oliveto, T. Paixao, J. Heredia, D. Sudholt, B. Trubenova, in:, Proceedings of the Genetic and Evolutionary Computation Conference 2016 , ACM, 2016, pp. 1163–1170.","mla":"Oliveto, Pietro, et al. “When Non-Elitism Outperforms Elitism for Crossing Fitness Valleys.” Proceedings of the Genetic and Evolutionary Computation Conference 2016 , ACM, 2016, pp. 1163–70, doi:10.1145/2908812.2908909.","chicago":"Oliveto, Pietro, Tiago Paixao, Jorge Heredia, Dirk Sudholt, and Barbora Trubenova. “When Non-Elitism Outperforms Elitism for Crossing Fitness Valleys.” In Proceedings of the Genetic and Evolutionary Computation Conference 2016 , 1163–70. ACM, 2016. https://doi.org/10.1145/2908812.2908909."},"publication":"Proceedings of the Genetic and Evolutionary Computation Conference 2016 ","date_published":"2016-07-20T00:00:00Z","type":"conference","abstract":[{"text":"Crossing fitness valleys is one of the major obstacles to function optimization. In this paper we investigate how the structure of the fitness valley, namely its depth d and length ℓ, influence the runtime of different strategies for crossing these valleys. We present a runtime comparison between the (1+1) EA and two non-elitist nature-inspired algorithms, Strong Selection Weak Mutation (SSWM) and the Metropolis algorithm. While the (1+1) EA has to jump across the valley to a point of higher fitness because it does not accept decreasing moves, the non-elitist algorithms may cross the valley by accepting worsening moves. We show that while the runtime of the (1+1) EA algorithm depends critically on the length of the valley, the runtimes of the non-elitist algorithms depend crucially only on the depth of the valley. In particular, the expected runtime of both SSWM and Metropolis is polynomial in ℓ and exponential in d while the (1+1) EA is efficient only for valleys of small length. Moreover, we show that both SSWM and Metropolis can also efficiently optimize a rugged function consisting of consecutive valleys.","lang":"eng"}],"title":"When non-elitism outperforms elitism for crossing fitness valleys","status":"public","ddc":["576"],"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","_id":"1349","oa_version":"Published Version","file":[{"file_size":979026,"content_type":"application/pdf","creator":"system","access_level":"open_access","file_name":"IST-2016-650-v1+1_p1163-oliveto.pdf","checksum":"a1896e39e4113f2711e46b435d5f3e69","date_updated":"2020-07-14T12:44:45Z","date_created":"2018-12-12T10:16:27Z","relation":"main_file","file_id":"5214"}],"pubrep_id":"650"},{"author":[{"full_name":"Paixao, Tiago","first_name":"Tiago","last_name":"Paixao","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2361-3953"},{"id":"4880FE40-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8548-5240","first_name":"Nicholas H","last_name":"Barton","full_name":"Barton, Nicholas H"}],"date_created":"2018-12-11T11:51:34Z","date_updated":"2021-01-12T06:50:08Z","volume":113,"year":"2016","pmid":1,"publication_status":"published","department":[{"_id":"NiBa"},{"_id":"CaGu"}],"publisher":"National Academy of Sciences","publist_id":"5886","ec_funded":1,"doi":"10.1073/pnas.1518830113","language":[{"iso":"eng"}],"external_id":{"pmid":["27044080"]},"main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4843425/","open_access":"1"}],"oa":1,"quality_controlled":"1","project":[{"_id":"25B07788-B435-11E9-9278-68D0E5697425","grant_number":"250152","name":"Limits to selection in biology and in evolutionary computation","call_identifier":"FP7"},{"_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","grant_number":"618091","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","call_identifier":"FP7"}],"month":"04","oa_version":"Published Version","_id":"1359","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","title":"The effect of gene interactions on the long-term response to selection","intvolume":" 113","abstract":[{"text":"The role of gene interactions in the evolutionary process has long\r\nbeen controversial. Although some argue that they are not of\r\nimportance, because most variation is additive, others claim that\r\ntheir effect in the long term can be substantial. Here, we focus on\r\nthe long-term effects of genetic interactions under directional\r\nselection assuming no mutation or dominance, and that epistasis is\r\nsymmetrical overall. We ask by how much the mean of a complex\r\ntrait can be increased by selection and analyze two extreme\r\nregimes, in which either drift or selection dominate the dynamics\r\nof allele frequencies. In both scenarios, epistatic interactions affect\r\nthe long-term response to selection by modulating the additive\r\ngenetic variance. When drift dominates, we extend Robertson\r\n’\r\ns\r\n[Robertson A (1960)\r\nProc R Soc Lond B Biol Sci\r\n153(951):234\r\n−\r\n249]\r\nargument to show that, for any form of epistasis, the total response\r\nof a haploid population is proportional to the initial total genotypic\r\nvariance. In contrast, the total response of a diploid population is\r\nincreased by epistasis, for a given initial genotypic variance. When\r\nselection dominates, we show that the total selection response can\r\nonly be increased by epistasis when s\r\nome initially deleterious alleles\r\nbecome favored as the genetic background changes. We find a sim-\r\nple approximation for this effect and show that, in this regime, it is\r\nthe structure of the genotype - phenotype map that matters and not\r\nthe variance components of the population.","lang":"eng"}],"issue":"16","type":"journal_article","date_published":"2016-04-19T00:00:00Z","publication":"PNAS","citation":{"mla":"Paixao, Tiago, and Nicholas H. Barton. “The Effect of Gene Interactions on the Long-Term Response to Selection.” PNAS, vol. 113, no. 16, National Academy of Sciences, 2016, pp. 4422–27, doi:10.1073/pnas.1518830113.","short":"T. Paixao, N.H. Barton, PNAS 113 (2016) 4422–4427.","chicago":"Paixao, Tiago, and Nicholas H Barton. “The Effect of Gene Interactions on the Long-Term Response to Selection.” PNAS. National Academy of Sciences, 2016. https://doi.org/10.1073/pnas.1518830113.","ama":"Paixao T, Barton NH. The effect of gene interactions on the long-term response to selection. PNAS. 2016;113(16):4422-4427. doi:10.1073/pnas.1518830113","ista":"Paixao T, Barton NH. 2016. The effect of gene interactions on the long-term response to selection. PNAS. 113(16), 4422–4427.","apa":"Paixao, T., & Barton, N. H. (2016). The effect of gene interactions on the long-term response to selection. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.1518830113","ieee":"T. Paixao and N. H. Barton, “The effect of gene interactions on the long-term response to selection,” PNAS, vol. 113, no. 16. National Academy of Sciences, pp. 4422–4427, 2016."},"article_type":"original","page":"4422 - 4427","day":"19","article_processing_charge":"No","scopus_import":1},{"file_date_updated":"2020-07-14T12:44:53Z","ec_funded":1,"publist_id":"5772","author":[{"id":"345D25EC-F248-11E8-B48F-1D18A9856A87","first_name":"Mato","last_name":"Lagator","full_name":"Lagator, Mato"},{"id":"46613666-F248-11E8-B48F-1D18A9856A87","first_name":"Claudia","last_name":"Igler","full_name":"Igler, Claudia"},{"full_name":"Moreno, Anaisa","last_name":"Moreno","first_name":"Anaisa"},{"full_name":"Guet, Calin C","last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Bollback, Jonathan P","last_name":"Bollback","first_name":"Jonathan P","orcid":"0000-0002-4624-4612","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87"}],"date_updated":"2021-01-12T06:50:39Z","date_created":"2018-12-11T11:51:57Z","volume":33,"year":"2016","publication_status":"published","publisher":"Oxford University Press","department":[{"_id":"CaGu"},{"_id":"JoBo"}],"month":"03","doi":"10.1093/molbev/msv269","language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"quality_controlled":"1","project":[{"name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734"}],"abstract":[{"lang":"eng","text":"Changes in gene expression are an important mode of evolution; however, the proximate mechanism of these changes is poorly understood. In particular, little is known about the effects of mutations within cis binding sites for transcription factors, or the nature of epistatic interactions between these mutations. Here, we tested the effects of single and double mutants in two cis binding sites involved in the transcriptional regulation of the Escherichia coli araBAD operon, a component of arabinose metabolism, using a synthetic system. This system decouples transcriptional control from any posttranslational effects on fitness, allowing a precise estimate of the effect of single and double mutations, and hence epistasis, on gene expression. We found that epistatic interactions between mutations in the araBAD cis-regulatory element are common, and that the predominant form of epistasis is negative. The magnitude of the interactions depended on whether the mutations are located in the same or in different operator sites. Importantly, these epistatic interactions were dependent on the presence of arabinose, a native inducer of the araBAD operon in vivo, with some interactions changing in sign (e.g., from negative to positive) in its presence. This study thus reveals that mutations in even relatively simple cis-regulatory elements interact in complex ways such that selection on the level of gene expression in one environment might perturb regulation in the other environment in an unpredictable and uncorrelated manner."}],"issue":"3","type":"journal_article","pubrep_id":"588","file":[{"creator":"system","file_size":648115,"content_type":"application/pdf","access_level":"open_access","file_name":"IST-2016-588-v1+1_Mol_Biol_Evol-2016-Lagator-761-9.pdf","checksum":"1f456ce1d2aa2f67176a1709f9702ecf","date_created":"2018-12-12T10:09:27Z","date_updated":"2020-07-14T12:44:53Z","file_id":"4751","relation":"main_file"}],"oa_version":"Published Version","_id":"1427","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","ddc":["570","576"],"title":"Epistatic interactions in the arabinose cis-regulatory element","status":"public","intvolume":" 33","day":"01","has_accepted_license":"1","scopus_import":1,"date_published":"2016-03-01T00:00:00Z","publication":"Molecular Biology and Evolution","citation":{"chicago":"Lagator, Mato, Claudia Igler, Anaisa Moreno, Calin C Guet, and Jonathan P Bollback. “Epistatic Interactions in the Arabinose Cis-Regulatory Element.” Molecular Biology and Evolution. Oxford University Press, 2016. https://doi.org/10.1093/molbev/msv269.","short":"M. Lagator, C. Igler, A. Moreno, C.C. Guet, J.P. Bollback, Molecular Biology and Evolution 33 (2016) 761–769.","mla":"Lagator, Mato, et al. “Epistatic Interactions in the Arabinose Cis-Regulatory Element.” Molecular Biology and Evolution, vol. 33, no. 3, Oxford University Press, 2016, pp. 761–69, doi:10.1093/molbev/msv269.","ieee":"M. Lagator, C. Igler, A. Moreno, C. C. Guet, and J. P. Bollback, “Epistatic interactions in the arabinose cis-regulatory element,” Molecular Biology and Evolution, vol. 33, no. 3. Oxford University Press, pp. 761–769, 2016.","apa":"Lagator, M., Igler, C., Moreno, A., Guet, C. C., & Bollback, J. P. (2016). Epistatic interactions in the arabinose cis-regulatory element. Molecular Biology and Evolution. Oxford University Press. https://doi.org/10.1093/molbev/msv269","ista":"Lagator M, Igler C, Moreno A, Guet CC, Bollback JP. 2016. Epistatic interactions in the arabinose cis-regulatory element. Molecular Biology and Evolution. 33(3), 761–769.","ama":"Lagator M, Igler C, Moreno A, Guet CC, Bollback JP. Epistatic interactions in the arabinose cis-regulatory element. Molecular Biology and Evolution. 2016;33(3):761-769. doi:10.1093/molbev/msv269"},"page":"761 - 769"},{"_id":"1524","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","intvolume":" 9271","status":"public","title":"Efficient reduction of kappa models by static inspection of the rule-set","oa_version":"Preprint","type":"conference","alternative_title":["LNCS"],"abstract":[{"lang":"eng","text":"When designing genetic circuits, the typical primitives used in major existing modelling formalisms are gene interaction graphs, where edges between genes denote either an activation or inhibition relation. However, when designing experiments, it is important to be precise about the low-level mechanistic details as to how each such relation is implemented. The rule-based modelling language Kappa allows to unambiguously specify mechanistic details such as DNA binding sites, dimerisation of transcription factors, or co-operative interactions. Such a detailed description comes with complexity and computationally costly executions. We propose a general method for automatically transforming a rule-based program, by eliminating intermediate species and adjusting the rate constants accordingly. To the best of our knowledge, we show the first automated reduction of rule-based models based on equilibrium approximations.\r\nOur algorithm is an adaptation of an existing algorithm, which was designed for reducing reaction-based programs; our version of the algorithm scans the rule-based Kappa model in search for those interaction patterns known to be amenable to equilibrium approximations (e.g. Michaelis-Menten scheme). Additional checks are then performed in order to verify if the reduction is meaningful in the context of the full model. The reduced model is efficiently obtained by static inspection over the rule-set. The tool is tested on a detailed rule-based model of a λ-phage switch, which lists 92 rules and 13 agents. The reduced model has 11 rules and 5 agents, and provides a dramatic reduction in simulation time of several orders of magnitude."}],"citation":{"ieee":"A. Beica, C. C. Guet, and T. Petrov, “Efficient reduction of kappa models by static inspection of the rule-set,” presented at the HSB: Hybrid Systems Biology, Madrid, Spain, 2016, vol. 9271, pp. 173–191.","apa":"Beica, A., Guet, C. C., & Petrov, T. (2016). Efficient reduction of kappa models by static inspection of the rule-set (Vol. 9271, pp. 173–191). Presented at the HSB: Hybrid Systems Biology, Madrid, Spain: Springer. https://doi.org/10.1007/978-3-319-26916-0_10","ista":"Beica A, Guet CC, Petrov T. 2016. Efficient reduction of kappa models by static inspection of the rule-set. HSB: Hybrid Systems Biology, LNCS, vol. 9271, 173–191.","ama":"Beica A, Guet CC, Petrov T. Efficient reduction of kappa models by static inspection of the rule-set. In: Vol 9271. Springer; 2016:173-191. doi:10.1007/978-3-319-26916-0_10","chicago":"Beica, Andreea, Calin C Guet, and Tatjana Petrov. “Efficient Reduction of Kappa Models by Static Inspection of the Rule-Set,” 9271:173–91. Springer, 2016. https://doi.org/10.1007/978-3-319-26916-0_10.","short":"A. Beica, C.C. Guet, T. Petrov, in:, Springer, 2016, pp. 173–191.","mla":"Beica, Andreea, et al. Efficient Reduction of Kappa Models by Static Inspection of the Rule-Set. Vol. 9271, Springer, 2016, pp. 173–91, doi:10.1007/978-3-319-26916-0_10."},"page":"173 - 191","date_published":"2016-01-10T00:00:00Z","scopus_import":1,"day":"10","acknowledgement":"This research was supported by the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. 291734, and the SNSF Early Postdoc.Mobility Fellowship, the grant number P2EZP2_148797.","year":"2016","publisher":"Springer","department":[{"_id":"CaGu"},{"_id":"ToHe"}],"publication_status":"published","author":[{"full_name":"Beica, Andreea","last_name":"Beica","first_name":"Andreea"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet","full_name":"Guet, Calin C"},{"first_name":"Tatjana","last_name":"Petrov","id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9041-0905","full_name":"Petrov, Tatjana"}],"volume":9271,"date_created":"2018-12-11T11:52:31Z","date_updated":"2021-01-12T06:51:22Z","publist_id":"5649","ec_funded":1,"oa":1,"main_file_link":[{"url":"http://arxiv.org/abs/1501.00440","open_access":"1"}],"project":[{"_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734","name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7"}],"quality_controlled":"1","doi":"10.1007/978-3-319-26916-0_10","conference":{"end_date":"2015-09-05","start_date":"2015-09-04","location":"Madrid, Spain","name":"HSB: Hybrid Systems Biology"},"language":[{"iso":"eng"}],"month":"01"},{"date_published":"2016-04-19T00:00:00Z","publication":"PLoS Genetics","citation":{"chicago":"Boehm, Alex, Markus Arnoldini, Tobias Bergmiller, Thomas Röösli, Colette Bigosch, and Martin Ackermann. “Genetic Manipulation of Glycogen Allocation Affects Replicative Lifespan in E Coli.” PLoS Genetics. Public Library of Science, 2016. https://doi.org/10.1371/journal.pgen.1005974.","short":"A. Boehm, M. Arnoldini, T. Bergmiller, T. Röösli, C. Bigosch, M. Ackermann, PLoS Genetics 12 (2016).","mla":"Boehm, Alex, et al. “Genetic Manipulation of Glycogen Allocation Affects Replicative Lifespan in E Coli.” PLoS Genetics, vol. 12, no. 4, e1005974, Public Library of Science, 2016, doi:10.1371/journal.pgen.1005974.","ieee":"A. Boehm, M. Arnoldini, T. Bergmiller, T. Röösli, C. Bigosch, and M. Ackermann, “Genetic manipulation of glycogen allocation affects replicative lifespan in E coli,” PLoS Genetics, vol. 12, no. 4. Public Library of Science, 2016.","apa":"Boehm, A., Arnoldini, M., Bergmiller, T., Röösli, T., Bigosch, C., & Ackermann, M. (2016). Genetic manipulation of glycogen allocation affects replicative lifespan in E coli. PLoS Genetics. Public Library of Science. https://doi.org/10.1371/journal.pgen.1005974","ista":"Boehm A, Arnoldini M, Bergmiller T, Röösli T, Bigosch C, Ackermann M. 2016. Genetic manipulation of glycogen allocation affects replicative lifespan in E coli. PLoS Genetics. 12(4), e1005974.","ama":"Boehm A, Arnoldini M, Bergmiller T, Röösli T, Bigosch C, Ackermann M. Genetic manipulation of glycogen allocation affects replicative lifespan in E coli. PLoS Genetics. 2016;12(4). doi:10.1371/journal.pgen.1005974"},"day":"19","has_accepted_license":"1","scopus_import":1,"pubrep_id":"705","file":[{"file_size":6273249,"content_type":"application/pdf","creator":"system","file_name":"IST-2016-705-v1+1_journal.pgen.1005974.PDF","access_level":"open_access","date_updated":"2020-07-14T12:44:41Z","date_created":"2018-12-12T10:14:17Z","checksum":"53d22b2b39e5adc243d34f18b2615a85","relation":"main_file","file_id":"5067"}],"oa_version":"Published Version","_id":"1250","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","ddc":["576","579"],"title":"Genetic manipulation of glycogen allocation affects replicative lifespan in E coli","status":"public","intvolume":" 12","abstract":[{"text":"In bacteria, replicative aging manifests as a difference in growth or survival between the two cells emerging from division. One cell can be regarded as an aging mother with a decreased potential for future survival and division, the other as a rejuvenated daughter. Here, we aimed at investigating some of the processes involved in aging in the bacterium Escherichia coli, where the two types of cells can be distinguished by the age of their cell poles. We found that certain changes in the regulation of the carbohydrate metabolism can affect aging. A mutation in the carbon storage regulator gene, csrA, leads to a dramatically shorter replicative lifespan; csrA mutants stop dividing once their pole exceeds an age of about five divisions. These old-pole cells accumulate glycogen at their old cell poles; after their last division, they do not contain a chromosome, presumably because of spatial exclusion by the glycogen aggregates. The new-pole daughters produced by these aging mothers are born young; they only express the deleterious phenotype once their pole is old. These results demonstrate how manipulations of nutrient allocation can lead to the exclusion of the chromosome and limit replicative lifespan in E. coli, and illustrate how mutations can have phenotypic effects that are specific for cells with old poles. This raises the question how bacteria can avoid the accumulation of such mutations in their genomes over evolutionary times, and how they can achieve the long replicative lifespans that have recently been reported.","lang":"eng"}],"issue":"4","type":"journal_article","doi":"10.1371/journal.pgen.1005974","language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"quality_controlled":"1","month":"04","author":[{"first_name":"Alex","last_name":"Boehm","full_name":"Boehm, Alex"},{"first_name":"Markus","last_name":"Arnoldini","full_name":"Arnoldini, Markus"},{"orcid":"0000-0001-5396-4346","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","last_name":"Bergmiller","first_name":"Tobias","full_name":"Bergmiller, Tobias"},{"last_name":"Röösli","first_name":"Thomas","full_name":"Röösli, Thomas"},{"first_name":"Colette","last_name":"Bigosch","full_name":"Bigosch, Colette"},{"full_name":"Ackermann, Martin","last_name":"Ackermann","first_name":"Martin"}],"related_material":{"record":[{"status":"public","relation":"research_data","id":"9873"}]},"date_updated":"2023-02-23T14:11:39Z","date_created":"2018-12-11T11:50:56Z","volume":12,"year":"2016","acknowledgement":"This manuscript is dedicated to the memory of Alex Böhm, who was a great friend and a passionate biologist. Alex passed away after the initial submission of this manuscript. We thank Vesna Olivera and Ursula Sauder from the Zentrum für Mikroskopie Uni Basel for excellent service, and Olin Silander, Nikki Freed, and Nela Nikolic for helpful discussions. This work was supported by the Swiss National Science Foundation grants to M. Ackermann and Urs Jenal (supporting AB).","publication_status":"published","publisher":"Public Library of Science","department":[{"_id":"CaGu"}],"file_date_updated":"2020-07-14T12:44:41Z","publist_id":"6077","article_number":"e1005974"},{"publisher":"Public Library of Science","department":[{"_id":"CaGu"}],"title":"Quantification of the growth rate reduction as a consequence of age-specific mortality","status":"public","_id":"9873","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","year":"2016","oa_version":"Published Version","date_updated":"2023-02-21T16:50:13Z","date_created":"2021-08-10T09:42:34Z","related_material":{"record":[{"relation":"used_in_publication","status":"public","id":"1250"}]},"author":[{"last_name":"Boehm","first_name":"Alex","full_name":"Boehm, Alex"},{"last_name":"Arnoldini","first_name":"Markus","full_name":"Arnoldini, Markus"},{"orcid":"0000-0001-5396-4346","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","last_name":"Bergmiller","first_name":"Tobias","full_name":"Bergmiller, Tobias"},{"full_name":"Röösli, Thomas","last_name":"Röösli","first_name":"Thomas"},{"first_name":"Colette","last_name":"Bigosch","full_name":"Bigosch, Colette"},{"last_name":"Ackermann","first_name":"Martin","full_name":"Ackermann, Martin"}],"type":"research_data_reference","citation":{"ista":"Boehm A, Arnoldini M, Bergmiller T, Röösli T, Bigosch C, Ackermann M. 2016. Quantification of the growth rate reduction as a consequence of age-specific mortality, Public Library of Science, 10.1371/journal.pgen.1005974.s015.","ieee":"A. Boehm, M. Arnoldini, T. Bergmiller, T. Röösli, C. Bigosch, and M. Ackermann, “Quantification of the growth rate reduction as a consequence of age-specific mortality.” Public Library of Science, 2016.","apa":"Boehm, A., Arnoldini, M., Bergmiller, T., Röösli, T., Bigosch, C., & Ackermann, M. (2016). Quantification of the growth rate reduction as a consequence of age-specific mortality. Public Library of Science. https://doi.org/10.1371/journal.pgen.1005974.s015","ama":"Boehm A, Arnoldini M, Bergmiller T, Röösli T, Bigosch C, Ackermann M. Quantification of the growth rate reduction as a consequence of age-specific mortality. 2016. doi:10.1371/journal.pgen.1005974.s015","chicago":"Boehm, Alex, Markus Arnoldini, Tobias Bergmiller, Thomas Röösli, Colette Bigosch, and Martin Ackermann. “Quantification of the Growth Rate Reduction as a Consequence of Age-Specific Mortality.” Public Library of Science, 2016. https://doi.org/10.1371/journal.pgen.1005974.s015.","mla":"Boehm, Alex, et al. Quantification of the Growth Rate Reduction as a Consequence of Age-Specific Mortality. Public Library of Science, 2016, doi:10.1371/journal.pgen.1005974.s015.","short":"A. Boehm, M. Arnoldini, T. Bergmiller, T. Röösli, C. Bigosch, M. Ackermann, (2016)."},"doi":"10.1371/journal.pgen.1005974.s015","article_processing_charge":"No","month":"04","day":"19"},{"_id":"5749","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","title":"Adaptation to parasites and costs of parasite resistance in mutator and nonmutator bacteria","status":"public","ddc":["576"],"intvolume":" 33","pubrep_id":"587","file":[{"file_name":"2016_MolBiolEvol_Wielgoss.pdf","access_level":"open_access","creator":"dernst","file_size":634037,"content_type":"application/pdf","file_id":"5750","relation":"main_file","date_created":"2018-12-18T13:21:45Z","date_updated":"2020-07-14T12:47:10Z","checksum":"47d9010690b6c5c17f2ac830cc63ac5c"}],"oa_version":"Published Version","type":"journal_article","abstract":[{"lang":"eng","text":"Parasitism creates selection for resistance mechanisms in host populations and is hypothesized to promote increased host evolvability. However, the influence of these traits on host evolution when parasites are no longer present is unclear. We used experimental evolution and whole-genome sequencing of Escherichia coli to determine the effects of past and present exposure to parasitic viruses (phages) on the spread of mutator alleles, resistance, and bacterial competitive fitness. We found that mutator alleles spread rapidly during adaptation to any of four different phage species, and this pattern was even more pronounced with multiple phages present simultaneously. However, hypermutability did not detectably accelerate adaptation in the absence of phages and recovery of fitness costs associated with resistance. Several lineages evolved phage resistance through elevated mucoidy, and during subsequent evolution in phage-free conditions they rapidly reverted to nonmucoid, phage-susceptible phenotypes. Genome sequencing revealed that this phenotypic reversion was achieved by additional genetic changes rather than by genotypic reversion of the initial resistance mutations. Insertion sequence (IS) elements played a key role in both the acquisition of resistance and adaptation in the absence of parasites; unlike single nucleotide polymorphisms, IS insertions were not more frequent in mutator lineages. Our results provide a genetic explanation for rapid reversion of mucoidy, a phenotype observed in other bacterial species including human pathogens. Moreover, this demonstrates that the types of genetic change underlying adaptation to fitness costs, and consequently the impact of evolvability mechanisms such as increased point-mutation rates, depend critically on the mechanism of resistance."}],"issue":"3","publication":"Molecular Biology and Evolution","citation":{"chicago":"Wielgoss, Sébastien, Tobias Bergmiller, Anna M. Bischofberger, and Alex R. Hall. “Adaptation to Parasites and Costs of Parasite Resistance in Mutator and Nonmutator Bacteria.” Molecular Biology and Evolution. Oxford University Press, 2016. https://doi.org/10.1093/molbev/msv270.","short":"S. Wielgoss, T. Bergmiller, A.M. Bischofberger, A.R. Hall, Molecular Biology and Evolution 33 (2016) 770–782.","mla":"Wielgoss, Sébastien, et al. “Adaptation to Parasites and Costs of Parasite Resistance in Mutator and Nonmutator Bacteria.” Molecular Biology and Evolution, vol. 33, no. 3, Oxford University Press, 2016, pp. 770–82, doi:10.1093/molbev/msv270.","apa":"Wielgoss, S., Bergmiller, T., Bischofberger, A. M., & Hall, A. R. (2016). Adaptation to parasites and costs of parasite resistance in mutator and nonmutator bacteria. Molecular Biology and Evolution. Oxford University Press. https://doi.org/10.1093/molbev/msv270","ieee":"S. Wielgoss, T. Bergmiller, A. M. Bischofberger, and A. R. Hall, “Adaptation to parasites and costs of parasite resistance in mutator and nonmutator bacteria,” Molecular Biology and Evolution, vol. 33, no. 3. Oxford University Press, pp. 770–782, 2016.","ista":"Wielgoss S, Bergmiller T, Bischofberger AM, Hall AR. 2016. Adaptation to parasites and costs of parasite resistance in mutator and nonmutator bacteria. Molecular Biology and Evolution. 33(3), 770–782.","ama":"Wielgoss S, Bergmiller T, Bischofberger AM, Hall AR. Adaptation to parasites and costs of parasite resistance in mutator and nonmutator bacteria. Molecular Biology and Evolution. 2016;33(3):770-782. doi:10.1093/molbev/msv270"},"page":"770-782","date_published":"2016-03-01T00:00:00Z","scopus_import":"1","day":"01","article_processing_charge":"No","has_accepted_license":"1","year":"2016","acknowledgement":"The authors thank three anonymous reviewers and the editor for helpful comments on the manuscript, as well as Dominique Schneider for feedback on an earlier draft, Jenna Gallie for lytic λ and Julien Capelle for T5 and T6. This work was supported by the Swiss National Science Foundation (PZ00P3_148255 to A.H.) and an EU Marie Curie PEOPLE Postdoctoral Fellowship for Career Development (FP7-PEOPLE-2012-IEF-331824 to S.W.).","pmid":1,"publication_status":"published","publisher":"Oxford University Press","department":[{"_id":"CaGu"}],"author":[{"full_name":"Wielgoss, Sébastien","first_name":"Sébastien","last_name":"Wielgoss"},{"first_name":"Tobias","last_name":"Bergmiller","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5396-4346","full_name":"Bergmiller, Tobias"},{"last_name":"Bischofberger","first_name":"Anna M.","full_name":"Bischofberger, Anna M."},{"full_name":"Hall, Alex R.","first_name":"Alex R.","last_name":"Hall"}],"related_material":{"record":[{"id":"9719","status":"public","relation":"research_data"}]},"date_updated":"2023-09-05T13:46:05Z","date_created":"2018-12-18T13:18:10Z","volume":33,"file_date_updated":"2020-07-14T12:47:10Z","license":"https://creativecommons.org/licenses/by-nc/4.0/","oa":1,"tmp":{"name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","image":"/images/cc_by_nc.png","short":"CC BY-NC (4.0)"},"external_id":{"pmid":["26609077"]},"quality_controlled":"1","doi":"10.1093/molbev/msv270","language":[{"iso":"eng"}],"month":"03","publication_identifier":{"eissn":["1537-1719"],"issn":["0737-4038"]}},{"publication_status":"published","department":[{"_id":"ToHe"},{"_id":"KrCh"},{"_id":"CaGu"}],"publisher":"Schloss Dagstuhl - Leibniz-Zentrum für Informatik","year":"2016","acknowledgement":"This research was funded in part by the European Research Council (ERC) under grant agreement 267989\r\n(QUAREM), the Austrian Science Fund (FWF) under grants project S11402-N23 (RiSE and SHiNE)\r\nand Z211-N23 (Wittgenstein Award), by the Czech Science Foundation Grant No. P202/12/G061, and\r\nby the SNSF Advanced Postdoc. Mobility Fellowship – grant number P300P2_161067.","date_created":"2018-12-11T11:50:06Z","date_updated":"2023-09-07T11:58:33Z","volume":59,"author":[{"full_name":"Daca, Przemyslaw","first_name":"Przemyslaw","last_name":"Daca","id":"49351290-F248-11E8-B48F-1D18A9856A87"},{"id":"40876CD8-F248-11E8-B48F-1D18A9856A87","orcid":"0000−0002−2985−7724","first_name":"Thomas A","last_name":"Henzinger","full_name":"Henzinger, Thomas A"},{"id":"44CEF464-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8122-2881","first_name":"Jan","last_name":"Kretinsky","full_name":"Kretinsky, Jan"},{"id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9041-0905","first_name":"Tatjana","last_name":"Petrov","full_name":"Petrov, Tatjana"}],"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"1155"}]},"article_number":"20","file_date_updated":"2018-12-12T10:11:39Z","publist_id":"6283","ec_funded":1,"quality_controlled":"1","project":[{"name":"Quantitative Reactive Modeling","call_identifier":"FP7","grant_number":"267989","_id":"25EE3708-B435-11E9-9278-68D0E5697425"},{"_id":"25832EC2-B435-11E9-9278-68D0E5697425","grant_number":"S 11407_N23","name":"Rigorous Systems Engineering","call_identifier":"FWF"},{"_id":"25F42A32-B435-11E9-9278-68D0E5697425","grant_number":"Z211","call_identifier":"FWF","name":"The Wittgenstein Prize"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"language":[{"iso":"eng"}],"conference":{"name":"CONCUR: Concurrency Theory","start_date":"2016-08-23","location":"Quebec City; Canada","end_date":"2016-08-26"},"doi":"10.4230/LIPIcs.CONCUR.2016.20","month":"08","status":"public","title":"Linear distances between Markov chains","ddc":["004"],"intvolume":" 59","_id":"1093","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","file":[{"date_created":"2018-12-12T10:11:39Z","date_updated":"2018-12-12T10:11:39Z","file_id":"4895","relation":"main_file","creator":"system","file_size":501827,"content_type":"application/pdf","file_name":"IST-2017-794-v1+1_LIPIcs-CONCUR-2016-20.pdf","access_level":"open_access"}],"oa_version":"Published Version","pubrep_id":"794","alternative_title":["LIPIcs"],"type":"conference","abstract":[{"text":"We introduce a general class of distances (metrics) between Markov chains, which are based on linear behaviour. This class encompasses distances given topologically (such as the total variation distance or trace distance) as well as by temporal logics or automata. We investigate which of the distances can be approximated by observing the systems, i.e. by black-box testing or simulation, and we provide both negative and positive results. ","lang":"eng"}],"citation":{"ista":"Daca P, Henzinger TA, Kretinsky J, Petrov T. 2016. Linear distances between Markov chains. CONCUR: Concurrency Theory, LIPIcs, vol. 59, 20.","apa":"Daca, P., Henzinger, T. A., Kretinsky, J., & Petrov, T. (2016). Linear distances between Markov chains (Vol. 59). Presented at the CONCUR: Concurrency Theory, Quebec City; Canada: Schloss Dagstuhl - Leibniz-Zentrum für Informatik. https://doi.org/10.4230/LIPIcs.CONCUR.2016.20","ieee":"P. Daca, T. A. Henzinger, J. Kretinsky, and T. Petrov, “Linear distances between Markov chains,” presented at the CONCUR: Concurrency Theory, Quebec City; Canada, 2016, vol. 59.","ama":"Daca P, Henzinger TA, Kretinsky J, Petrov T. Linear distances between Markov chains. In: Vol 59. Schloss Dagstuhl - Leibniz-Zentrum für Informatik; 2016. doi:10.4230/LIPIcs.CONCUR.2016.20","chicago":"Daca, Przemyslaw, Thomas A Henzinger, Jan Kretinsky, and Tatjana Petrov. “Linear Distances between Markov Chains,” Vol. 59. Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2016. https://doi.org/10.4230/LIPIcs.CONCUR.2016.20.","mla":"Daca, Przemyslaw, et al. Linear Distances between Markov Chains. Vol. 59, 20, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2016, doi:10.4230/LIPIcs.CONCUR.2016.20.","short":"P. Daca, T.A. Henzinger, J. Kretinsky, T. Petrov, in:, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2016."},"date_published":"2016-08-01T00:00:00Z","scopus_import":1,"day":"01","has_accepted_license":"1"},{"month":"01","conference":{"start_date":"2016-04-02","location":"Eindhoven, The Netherlands","end_date":"2016-04-08","name":"TACAS: Tools and Algorithms for the Construction and Analysis of Systems"},"doi":"10.1007/978-3-662-49674-9_7","language":[{"iso":"eng"}],"oa":1,"main_file_link":[{"open_access":"1","url":"https://arxiv.org/abs/1504.05739"}],"quality_controlled":"1","project":[{"_id":"25EE3708-B435-11E9-9278-68D0E5697425","grant_number":"267989","name":"Quantitative Reactive Modeling","call_identifier":"FP7"},{"call_identifier":"FWF","name":"Rigorous Systems Engineering","grant_number":"S 11407_N23","_id":"25832EC2-B435-11E9-9278-68D0E5697425"},{"_id":"25F42A32-B435-11E9-9278-68D0E5697425","grant_number":"Z211","name":"The Wittgenstein Prize","call_identifier":"FWF"},{"grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425","name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7"}],"publist_id":"6099","ec_funded":1,"author":[{"full_name":"Daca, Przemyslaw","id":"49351290-F248-11E8-B48F-1D18A9856A87","first_name":"Przemyslaw","last_name":"Daca"},{"id":"40876CD8-F248-11E8-B48F-1D18A9856A87","orcid":"0000−0002−2985−7724","first_name":"Thomas A","last_name":"Henzinger","full_name":"Henzinger, Thomas A"},{"full_name":"Kretinsky, Jan","orcid":"0000-0002-8122-2881","id":"44CEF464-F248-11E8-B48F-1D18A9856A87","last_name":"Kretinsky","first_name":"Jan"},{"id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9041-0905","first_name":"Tatjana","last_name":"Petrov","full_name":"Petrov, Tatjana"}],"related_material":{"record":[{"relation":"later_version","status":"public","id":"471"},{"id":"1155","status":"public","relation":"dissertation_contains"}]},"date_updated":"2023-09-07T11:58:33Z","date_created":"2018-12-11T11:50:51Z","volume":9636,"acknowledgement":"This research was funded in part by the European Research Council (ERC) under\r\ngrant agreement 267989 (QUAREM), the Austrian Science Fund (FWF) under\r\ngrants project S11402-N23 (RiSE) and Z211-N23 (Wittgenstein Award), the Peo-\r\nple Programme (Marie Curie Actions) of the European Union’s Seventh Framework\r\nProgramme (FP7/2007-2013) REA Grant No 291734, the SNSF Advanced Postdoc.\r\nMobility Fellowship – grant number P300P2\r\n161067, and the Czech Science Foun-\r\ndation under grant agreement P202/12/G061.","year":"2016","publication_status":"published","department":[{"_id":"ToHe"},{"_id":"CaGu"}],"publisher":"Springer","day":"01","scopus_import":1,"date_published":"2016-01-01T00:00:00Z","citation":{"short":"P. Daca, T.A. Henzinger, J. Kretinsky, T. Petrov, in:, Springer, 2016, pp. 112–129.","mla":"Daca, Przemyslaw, et al. Faster Statistical Model Checking for Unbounded Temporal Properties. Vol. 9636, Springer, 2016, pp. 112–29, doi:10.1007/978-3-662-49674-9_7.","chicago":"Daca, Przemyslaw, Thomas A Henzinger, Jan Kretinsky, and Tatjana Petrov. “Faster Statistical Model Checking for Unbounded Temporal Properties,” 9636:112–29. Springer, 2016. https://doi.org/10.1007/978-3-662-49674-9_7.","ama":"Daca P, Henzinger TA, Kretinsky J, Petrov T. Faster statistical model checking for unbounded temporal properties. In: Vol 9636. Springer; 2016:112-129. doi:10.1007/978-3-662-49674-9_7","apa":"Daca, P., Henzinger, T. A., Kretinsky, J., & Petrov, T. (2016). Faster statistical model checking for unbounded temporal properties (Vol. 9636, pp. 112–129). Presented at the TACAS: Tools and Algorithms for the Construction and Analysis of Systems, Eindhoven, The Netherlands: Springer. https://doi.org/10.1007/978-3-662-49674-9_7","ieee":"P. Daca, T. A. Henzinger, J. Kretinsky, and T. Petrov, “Faster statistical model checking for unbounded temporal properties,” presented at the TACAS: Tools and Algorithms for the Construction and Analysis of Systems, Eindhoven, The Netherlands, 2016, vol. 9636, pp. 112–129.","ista":"Daca P, Henzinger TA, Kretinsky J, Petrov T. 2016. Faster statistical model checking for unbounded temporal properties. TACAS: Tools and Algorithms for the Construction and Analysis of Systems, LNCS, vol. 9636, 112–129."},"page":"112 - 129","abstract":[{"lang":"eng","text":"We present a new algorithm for the statistical model checking of Markov chains with respect to unbounded temporal properties, including full linear temporal logic. The main idea is that we monitor each simulation run on the fly, in order to detect quickly if a bottom strongly connected component is entered with high probability, in which case the simulation run can be terminated early. As a result, our simulation runs are often much shorter than required by termination bounds that are computed a priori for a desired level of confidence on a large state space. In comparison to previous algorithms for statistical model checking our method is not only faster in many cases but also requires less information about the system, namely, only the minimum transition probability that occurs in the Markov chain. In addition, our method can be generalised to unbounded quantitative properties such as mean-payoff bounds."}],"type":"conference","alternative_title":["LNCS"],"oa_version":"Preprint","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","_id":"1234","status":"public","title":"Faster statistical model checking for unbounded temporal properties","intvolume":" 9636"},{"publist_id":"6087","publisher":"Cell Press","department":[{"_id":"CaGu"}],"publication_status":"published","acknowledgement":"This work was funded by an HFSP Young Investigators’ grant. M.P. is a recipient of a DOC Fellowship of the Austrian Academy of Science at the Institute of Science and Technology Austria. R.O. and Y.W. were supported by the Platform for Dynamic Approaches to Living System from MEXT, Japan. We wish to thank I. Kobayashi for providing us with the EcoRI and EcoRV plasmids, and A. Campbell for providing us with the λ vir phage. We thank D. Siekhaus and C. Uhler and members of the C.C.G. and J.P. Bollback laboratories for in-depth discussions. We thank B. Stern for comments on an earlier version of the manuscript. We especially thank B.R. Levin for advice and comments, and the anonymous reviewers for significantly improving the manuscript.","year":"2016","volume":26,"date_created":"2018-12-11T11:50:54Z","date_updated":"2023-09-07T11:59:32Z","related_material":{"record":[{"id":"202","relation":"dissertation_contains","status":"public"}]},"author":[{"last_name":"Pleska","first_name":"Maros","orcid":"0000-0001-7460-7479","id":"4569785E-F248-11E8-B48F-1D18A9856A87","full_name":"Pleska, Maros"},{"first_name":"Long","last_name":"Qian","full_name":"Qian, Long"},{"last_name":"Okura","first_name":"Reiko","full_name":"Okura, Reiko"},{"first_name":"Tobias","last_name":"Bergmiller","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5396-4346","full_name":"Bergmiller, Tobias"},{"first_name":"Yuichi","last_name":"Wakamoto","full_name":"Wakamoto, Yuichi"},{"full_name":"Kussell, Edo","first_name":"Edo","last_name":"Kussell"},{"last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C"}],"month":"02","project":[{"name":"Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level (DOC Fellowship)","grant_number":"24210","_id":"251D65D8-B435-11E9-9278-68D0E5697425"}],"quality_controlled":"1","language":[{"iso":"eng"}],"doi":"10.1016/j.cub.2015.12.041","type":"journal_article","issue":"3","abstract":[{"lang":"eng","text":"Restriction-modification (RM) systems represent a minimal and ubiquitous biological system of self/non-self discrimination in prokaryotes [1], which protects hosts from exogenous DNA [2]. The mechanism is based on the balance between methyltransferase (M) and cognate restriction endonuclease (R). M tags endogenous DNA as self by methylating short specific DNA sequences called restriction sites, whereas R recognizes unmethylated restriction sites as non-self and introduces a double-stranded DNA break [3]. Restriction sites are significantly underrepresented in prokaryotic genomes [4-7], suggesting that the discrimination mechanism is imperfect and occasionally leads to autoimmunity due to self-DNA cleavage (self-restriction) [8]. Furthermore, RM systems can promote DNA recombination [9] and contribute to genetic variation in microbial populations, thus facilitating adaptive evolution [10]. However, cleavage of self-DNA by RM systems as elements shaping prokaryotic genomes has not been directly detected, and its cause, frequency, and outcome are unknown. We quantify self-restriction caused by two RM systems of Escherichia coli and find that, in agreement with levels of restriction site avoidance, EcoRI, but not EcoRV, cleaves self-DNA at a measurable rate. Self-restriction is a stochastic process, which temporarily induces the SOS response, and is followed by DNA repair, maintaining cell viability. We find that RM systems with higher restriction efficiency against bacteriophage infections exhibit a higher rate of self-restriction, and that this rate can be further increased by stochastic imbalance between R and M. Our results identify molecular noise in RM systems as a factor shaping prokaryotic genomes."}],"intvolume":" 26","status":"public","title":"Bacterial autoimmunity due to a restriction-modification system","_id":"1243","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","oa_version":"None","scopus_import":1,"day":"08","page":"404 - 409","citation":{"short":"M. Pleska, L. Qian, R. Okura, T. Bergmiller, Y. Wakamoto, E. Kussell, C.C. Guet, Current Biology 26 (2016) 404–409.","mla":"Pleska, Maros, et al. “Bacterial Autoimmunity Due to a Restriction-Modification System.” Current Biology, vol. 26, no. 3, Cell Press, 2016, pp. 404–09, doi:10.1016/j.cub.2015.12.041.","chicago":"Pleska, Maros, Long Qian, Reiko Okura, Tobias Bergmiller, Yuichi Wakamoto, Edo Kussell, and Calin C Guet. “Bacterial Autoimmunity Due to a Restriction-Modification System.” Current Biology. Cell Press, 2016. https://doi.org/10.1016/j.cub.2015.12.041.","ama":"Pleska M, Qian L, Okura R, et al. Bacterial autoimmunity due to a restriction-modification system. Current Biology. 2016;26(3):404-409. doi:10.1016/j.cub.2015.12.041","ieee":"M. Pleska et al., “Bacterial autoimmunity due to a restriction-modification system,” Current Biology, vol. 26, no. 3. Cell Press, pp. 404–409, 2016.","apa":"Pleska, M., Qian, L., Okura, R., Bergmiller, T., Wakamoto, Y., Kussell, E., & Guet, C. C. (2016). Bacterial autoimmunity due to a restriction-modification system. Current Biology. Cell Press. https://doi.org/10.1016/j.cub.2015.12.041","ista":"Pleska M, Qian L, Okura R, Bergmiller T, Wakamoto Y, Kussell E, Guet CC. 2016. Bacterial autoimmunity due to a restriction-modification system. Current Biology. 26(3), 404–409."},"publication":"Current Biology","date_published":"2016-02-08T00:00:00Z"},{"article_number":"12307","ec_funded":1,"publist_id":"5887","file_date_updated":"2020-07-14T12:44:46Z","department":[{"_id":"GaTk"},{"_id":"NiBa"},{"_id":"CaGu"}],"publisher":"Nature Publishing Group","publication_status":"published","year":"2016","volume":7,"date_updated":"2023-09-07T12:53:49Z","date_created":"2018-12-11T11:51:34Z","related_material":{"record":[{"id":"6071","relation":"dissertation_contains","status":"public"}]},"author":[{"full_name":"Friedlander, Tamar","last_name":"Friedlander","first_name":"Tamar","id":"36A5845C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Prizak","first_name":"Roshan","id":"4456104E-F248-11E8-B48F-1D18A9856A87","full_name":"Prizak, Roshan"},{"last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C"},{"orcid":"0000-0002-8548-5240","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","last_name":"Barton","first_name":"Nicholas H","full_name":"Barton, Nicholas H"},{"orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","last_name":"Tkacik","first_name":"Gasper","full_name":"Tkacik, Gasper"}],"month":"08","project":[{"name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425"},{"grant_number":"250152","_id":"25B07788-B435-11E9-9278-68D0E5697425","name":"Limits to selection in biology and in evolutionary computation","call_identifier":"FP7"},{"_id":"254E9036-B435-11E9-9278-68D0E5697425","grant_number":"P28844-B27","name":"Biophysics of information processing in gene regulation","call_identifier":"FWF"}],"quality_controlled":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"language":[{"iso":"eng"}],"doi":"10.1038/ncomms12307","type":"journal_article","abstract":[{"lang":"eng","text":"Gene regulation relies on the specificity of transcription factor (TF)–DNA interactions. Limited specificity may lead to crosstalk: a regulatory state in which a gene is either incorrectly activated due to noncognate TF–DNA interactions or remains erroneously inactive. As each TF can have numerous interactions with noncognate cis-regulatory elements, crosstalk is inherently a global problem, yet has previously not been studied as such. We construct a theoretical framework to analyse the effects of global crosstalk on gene regulation. We find that crosstalk presents a significant challenge for organisms with low-specificity TFs, such as metazoans. Crosstalk is not easily mitigated by known regulatory schemes acting at equilibrium, including variants of cooperativity and combinatorial regulation. Our results suggest that crosstalk imposes a previously unexplored global constraint on the functioning and evolution of regulatory networks, which is qualitatively distinct from the known constraints that act at the level of individual gene regulatory elements."}],"intvolume":" 7","status":"public","ddc":["576"],"title":"Intrinsic limits to gene regulation by global crosstalk","_id":"1358","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","oa_version":"Published Version","file":[{"checksum":"fe3f3a1526d180b29fe691ab11435b78","date_created":"2018-12-12T10:12:01Z","date_updated":"2020-07-14T12:44:46Z","relation":"main_file","file_id":"4919","file_size":861805,"content_type":"application/pdf","creator":"system","access_level":"open_access","file_name":"IST-2016-627-v1+1_ncomms12307.pdf"},{"date_created":"2018-12-12T10:12:02Z","date_updated":"2020-07-14T12:44:46Z","checksum":"164864a1a675f3ad80e9917c27aba07f","relation":"main_file","file_id":"4920","content_type":"application/pdf","file_size":1084703,"creator":"system","file_name":"IST-2016-627-v1+2_ncomms12307-s1.pdf","access_level":"open_access"}],"pubrep_id":"627","scopus_import":1,"has_accepted_license":"1","day":"04","citation":{"short":"T. Friedlander, R. Prizak, C.C. Guet, N.H. Barton, G. Tkačik, Nature Communications 7 (2016).","mla":"Friedlander, Tamar, et al. “Intrinsic Limits to Gene Regulation by Global Crosstalk.” Nature Communications, vol. 7, 12307, Nature Publishing Group, 2016, doi:10.1038/ncomms12307.","chicago":"Friedlander, Tamar, Roshan Prizak, Calin C Guet, Nicholas H Barton, and Gašper Tkačik. “Intrinsic Limits to Gene Regulation by Global Crosstalk.” Nature Communications. Nature Publishing Group, 2016. https://doi.org/10.1038/ncomms12307.","ama":"Friedlander T, Prizak R, Guet CC, Barton NH, Tkačik G. Intrinsic limits to gene regulation by global crosstalk. Nature Communications. 2016;7. doi:10.1038/ncomms12307","apa":"Friedlander, T., Prizak, R., Guet, C. C., Barton, N. H., & Tkačik, G. (2016). Intrinsic limits to gene regulation by global crosstalk. Nature Communications. Nature Publishing Group. https://doi.org/10.1038/ncomms12307","ieee":"T. Friedlander, R. Prizak, C. C. Guet, N. H. Barton, and G. Tkačik, “Intrinsic limits to gene regulation by global crosstalk,” Nature Communications, vol. 7. Nature Publishing Group, 2016.","ista":"Friedlander T, Prizak R, Guet CC, Barton NH, Tkačik G. 2016. Intrinsic limits to gene regulation by global crosstalk. Nature Communications. 7, 12307."},"publication":"Nature Communications","date_published":"2016-08-04T00:00:00Z"},{"date_updated":"2021-01-12T06:50:41Z","date_created":"2018-12-11T11:51:58Z","oa_version":"Preprint","author":[{"full_name":"Paixao, Tiago","last_name":"Paixao","first_name":"Tiago","orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Sudholt, Dirk","first_name":"Dirk","last_name":"Sudholt"},{"full_name":"Heredia, Jorge","first_name":"Jorge","last_name":"Heredia"},{"first_name":"Barbora","last_name":"Trubenova","id":"42302D54-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6873-2967","full_name":"Trubenova, Barbora"}],"publication_status":"published","status":"public","title":"First steps towards a runtime comparison of natural and artificial evolution","department":[{"_id":"NiBa"},{"_id":"CaGu"}],"publisher":"ACM","year":"2015","_id":"1430","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","abstract":[{"lang":"eng","text":"Evolutionary algorithms (EAs) form a popular optimisation paradigm inspired by natural evolution. In recent years the field of evolutionary computation has developed a rigorous analytical theory to analyse their runtime on many illustrative problems. Here we apply this theory to a simple model of natural evolution. In the Strong Selection Weak Mutation (SSWM) evolutionary regime the time between occurrence of new mutations is much longer than the time it takes for a new beneficial mutation to take over the population. In this situation, the population only contains copies of one genotype and evolution can be modelled as a (1+1)-type process where the probability of accepting a new genotype (improvements or worsenings) depends on the change in fitness. We present an initial runtime analysis of SSWM, quantifying its performance for various parameters and investigating differences to the (1+1) EA. We show that SSWM can have a moderate advantage over the (1+1) EA at crossing fitness valleys and study an example where SSWM outperforms the (1+1) EA by taking advantage of information on the fitness gradient."}],"ec_funded":1,"publist_id":"5768","type":"conference","language":[{"iso":"eng"}],"conference":{"location":"Madrid, Spain","start_date":"2015-07-11","end_date":"2015-07-15","name":"GECCO: Genetic and evolutionary computation conference"},"doi":"10.1145/2739480.2754758","date_published":"2015-07-11T00:00:00Z","quality_controlled":"1","project":[{"name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","call_identifier":"FP7","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","grant_number":"618091"}],"page":"1455 - 1462","publication":"Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation","citation":{"chicago":"Paixao, Tiago, Dirk Sudholt, Jorge Heredia, and Barbora Trubenova. “First Steps towards a Runtime Comparison of Natural and Artificial Evolution.” In Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation, 1455–62. ACM, 2015. https://doi.org/10.1145/2739480.2754758.","short":"T. Paixao, D. Sudholt, J. Heredia, B. Trubenova, in:, Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation, ACM, 2015, pp. 1455–1462.","mla":"Paixao, Tiago, et al. “First Steps towards a Runtime Comparison of Natural and Artificial Evolution.” Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation, ACM, 2015, pp. 1455–62, doi:10.1145/2739480.2754758.","ieee":"T. Paixao, D. Sudholt, J. Heredia, and B. Trubenova, “First steps towards a runtime comparison of natural and artificial evolution,” in Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation, Madrid, Spain, 2015, pp. 1455–1462.","apa":"Paixao, T., Sudholt, D., Heredia, J., & Trubenova, B. (2015). First steps towards a runtime comparison of natural and artificial evolution. In Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation (pp. 1455–1462). Madrid, Spain: ACM. https://doi.org/10.1145/2739480.2754758","ista":"Paixao T, Sudholt D, Heredia J, Trubenova B. 2015. First steps towards a runtime comparison of natural and artificial evolution. Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation. GECCO: Genetic and evolutionary computation conference, 1455–1462.","ama":"Paixao T, Sudholt D, Heredia J, Trubenova B. First steps towards a runtime comparison of natural and artificial evolution. In: Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation. ACM; 2015:1455-1462. doi:10.1145/2739480.2754758"},"oa":1,"main_file_link":[{"open_access":"1","url":"http://arxiv.org/abs/1504.06260"}],"day":"11","month":"07","scopus_import":1},{"author":[{"full_name":"Paixao, Tiago","last_name":"Paixao","first_name":"Tiago","orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Badkobeh","first_name":"Golnaz","full_name":"Badkobeh, Golnaz"},{"orcid":"0000-0002-8548-5240","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","last_name":"Barton","first_name":"Nicholas H","full_name":"Barton, Nicholas H"},{"full_name":"Çörüş, Doğan","last_name":"Çörüş","first_name":"Doğan"},{"last_name":"Dang","first_name":"Duccuong","full_name":"Dang, Duccuong"},{"full_name":"Friedrich, Tobias","last_name":"Friedrich","first_name":"Tobias"},{"full_name":"Lehre, Per","first_name":"Per","last_name":"Lehre"},{"full_name":"Sudholt, Dirk","last_name":"Sudholt","first_name":"Dirk"},{"first_name":"Andrew","last_name":"Sutton","full_name":"Sutton, Andrew"},{"last_name":"Trubenova","first_name":"Barbora","orcid":"0000-0002-6873-2967","id":"42302D54-F248-11E8-B48F-1D18A9856A87","full_name":"Trubenova, Barbora"}],"date_updated":"2021-01-12T06:51:29Z","date_created":"2018-12-11T11:52:37Z","volume":383,"year":"2015","publication_status":"published","department":[{"_id":"NiBa"},{"_id":"CaGu"}],"publisher":"Elsevier","file_date_updated":"2020-07-14T12:45:01Z","publist_id":"5629","ec_funded":1,"doi":"10.1016/j.jtbi.2015.07.011","language":[{"iso":"eng"}],"oa":1,"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"quality_controlled":"1","project":[{"name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","call_identifier":"FP7","grant_number":"618091","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425"},{"_id":"25B07788-B435-11E9-9278-68D0E5697425","grant_number":"250152","name":"Limits to selection in biology and in evolutionary computation","call_identifier":"FP7"}],"month":"10","pubrep_id":"483","oa_version":"Published Version","file":[{"relation":"main_file","file_id":"5244","date_created":"2018-12-12T10:16:53Z","date_updated":"2020-07-14T12:45:01Z","checksum":"33b60ecfea60764756a9ee9df5eb65ca","file_name":"IST-2016-483-v1+1_1-s2.0-S0022519315003409-main.pdf","access_level":"open_access","content_type":"application/pdf","file_size":595307,"creator":"system"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"1542","title":"Toward a unifying framework for evolutionary processes","ddc":["570"],"status":"public","intvolume":" 383","abstract":[{"text":"The theory of population genetics and evolutionary computation have been evolving separately for nearly 30 years. Many results have been independently obtained in both fields and many others are unique to its respective field. We aim to bridge this gap by developing a unifying framework for evolutionary processes that allows both evolutionary algorithms and population genetics models to be cast in the same formal framework. The framework we present here decomposes the evolutionary process into its several components in order to facilitate the identification of similarities between different models. In particular, we propose a classification of evolutionary operators based on the defining properties of the different components. We cast several commonly used operators from both fields into this common framework. Using this, we map different evolutionary and genetic algorithms to different evolutionary regimes and identify candidates with the most potential for the translation of results between the fields. This provides a unified description of evolutionary processes and represents a stepping stone towards new tools and results to both fields. ","lang":"eng"}],"type":"journal_article","date_published":"2015-10-21T00:00:00Z","publication":" Journal of Theoretical Biology","citation":{"chicago":"Paixao, Tiago, Golnaz Badkobeh, Nicholas H Barton, Doğan Çörüş, Duccuong Dang, Tobias Friedrich, Per Lehre, Dirk Sudholt, Andrew Sutton, and Barbora Trubenova. “Toward a Unifying Framework for Evolutionary Processes.” Journal of Theoretical Biology. Elsevier, 2015. https://doi.org/10.1016/j.jtbi.2015.07.011.","short":"T. Paixao, G. Badkobeh, N.H. Barton, D. Çörüş, D. Dang, T. Friedrich, P. Lehre, D. Sudholt, A. Sutton, B. Trubenova, Journal of Theoretical Biology 383 (2015) 28–43.","mla":"Paixao, Tiago, et al. “Toward a Unifying Framework for Evolutionary Processes.” Journal of Theoretical Biology, vol. 383, Elsevier, 2015, pp. 28–43, doi:10.1016/j.jtbi.2015.07.011.","apa":"Paixao, T., Badkobeh, G., Barton, N. H., Çörüş, D., Dang, D., Friedrich, T., … Trubenova, B. (2015). Toward a unifying framework for evolutionary processes. Journal of Theoretical Biology. Elsevier. https://doi.org/10.1016/j.jtbi.2015.07.011","ieee":"T. Paixao et al., “Toward a unifying framework for evolutionary processes,” Journal of Theoretical Biology, vol. 383. Elsevier, pp. 28–43, 2015.","ista":"Paixao T, Badkobeh G, Barton NH, Çörüş D, Dang D, Friedrich T, Lehre P, Sudholt D, Sutton A, Trubenova B. 2015. Toward a unifying framework for evolutionary processes. Journal of Theoretical Biology. 383, 28–43.","ama":"Paixao T, Badkobeh G, Barton NH, et al. Toward a unifying framework for evolutionary processes. Journal of Theoretical Biology. 2015;383:28-43. doi:10.1016/j.jtbi.2015.07.011"},"page":"28 - 43","day":"21","has_accepted_license":"1","scopus_import":1},{"day":"01","scopus_import":1,"date_published":"2015-04-01T00:00:00Z","publication":"IEEE Transactions on Automatic Control","citation":{"ista":"Geiger B, Petrov T, Kubin G, Koeppl H. 2015. Optimal Kullback-Leibler aggregation via information bottleneck. IEEE Transactions on Automatic Control. 60(4), 1010–1022.","apa":"Geiger, B., Petrov, T., Kubin, G., & Koeppl, H. (2015). Optimal Kullback-Leibler aggregation via information bottleneck. IEEE Transactions on Automatic Control. IEEE. https://doi.org/10.1109/TAC.2014.2364971","ieee":"B. Geiger, T. Petrov, G. Kubin, and H. Koeppl, “Optimal Kullback-Leibler aggregation via information bottleneck,” IEEE Transactions on Automatic Control, vol. 60, no. 4. IEEE, pp. 1010–1022, 2015.","ama":"Geiger B, Petrov T, Kubin G, Koeppl H. Optimal Kullback-Leibler aggregation via information bottleneck. IEEE Transactions on Automatic Control. 2015;60(4):1010-1022. doi:10.1109/TAC.2014.2364971","chicago":"Geiger, Bernhard, Tatjana Petrov, Gernot Kubin, and Heinz Koeppl. “Optimal Kullback-Leibler Aggregation via Information Bottleneck.” IEEE Transactions on Automatic Control. IEEE, 2015. https://doi.org/10.1109/TAC.2014.2364971.","mla":"Geiger, Bernhard, et al. “Optimal Kullback-Leibler Aggregation via Information Bottleneck.” IEEE Transactions on Automatic Control, vol. 60, no. 4, IEEE, 2015, pp. 1010–22, doi:10.1109/TAC.2014.2364971.","short":"B. Geiger, T. Petrov, G. Kubin, H. Koeppl, IEEE Transactions on Automatic Control 60 (2015) 1010–1022."},"page":"1010 - 1022","abstract":[{"lang":"eng","text":"In this paper, we present a method for reducing a regular, discrete-time Markov chain (DTMC) to another DTMC with a given, typically much smaller number of states. The cost of reduction is defined as the Kullback-Leibler divergence rate between a projection of the original process through a partition function and a DTMC on the correspondingly partitioned state space. Finding the reduced model with minimal cost is computationally expensive, as it requires an exhaustive search among all state space partitions, and an exact evaluation of the reduction cost for each candidate partition. Our approach deals with the latter problem by minimizing an upper bound on the reduction cost instead of minimizing the exact cost. The proposed upper bound is easy to compute and it is tight if the original chain is lumpable with respect to the partition. Then, we express the problem in the form of information bottleneck optimization, and propose using the agglomerative information bottleneck algorithm for searching a suboptimal partition greedily, rather than exhaustively. The theory is illustrated with examples and one application scenario in the context of modeling bio-molecular interactions."}],"issue":"4","type":"journal_article","oa_version":"Preprint","_id":"1840","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Optimal Kullback-Leibler aggregation via information bottleneck","status":"public","intvolume":" 60","month":"04","publication_identifier":{"issn":["0018-9286"]},"doi":"10.1109/TAC.2014.2364971","language":[{"iso":"eng"}],"main_file_link":[{"open_access":"1","url":"http://arxiv.org/abs/1304.6603"}],"oa":1,"quality_controlled":"1","publist_id":"5262","author":[{"first_name":"Bernhard","last_name":"Geiger","full_name":"Geiger, Bernhard"},{"full_name":"Petrov, Tatjana","id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9041-0905","first_name":"Tatjana","last_name":"Petrov"},{"full_name":"Kubin, Gernot","first_name":"Gernot","last_name":"Kubin"},{"first_name":"Heinz","last_name":"Koeppl","full_name":"Koeppl, Heinz"}],"date_created":"2018-12-11T11:54:18Z","date_updated":"2021-01-12T06:53:33Z","volume":60,"year":"2015","acknowledgement":"This work was supported by the Austrian Research Association under Project 06/12684, by the Swiss National Science Foundation (SNSF) under Grant PP00P2 128503/1, by the SystemsX.ch (the Swiss Inititative for Systems Biology), and by a SNSF Early Postdoc.Mobility Fellowship grant P2EZP2_148797.\r\n","publication_status":"published","department":[{"_id":"CaGu"},{"_id":"ToHe"}],"publisher":"IEEE"},{"date_created":"2021-07-23T12:00:37Z","date_updated":"2023-02-23T10:09:08Z","oa_version":"Published Version","author":[{"full_name":"Tugrul, Murat","last_name":"Tugrul","first_name":"Murat","orcid":"0000-0002-8523-0758","id":"37C323C6-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Paixao, Tiago","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2361-3953","first_name":"Tiago","last_name":"Paixao"},{"full_name":"Barton, Nicholas H","first_name":"Nicholas H","last_name":"Barton","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8548-5240"},{"full_name":"Tkačik, Gašper","last_name":"Tkačik","first_name":"Gašper","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"}],"related_material":{"record":[{"status":"public","relation":"used_in_publication","id":"1666"}]},"status":"public","title":"Other fitness models for comparison & for interacting TFBSs","publisher":"Public Library of Science","department":[{"_id":"NiBa"},{"_id":"CaGu"},{"_id":"GaTk"}],"_id":"9712","year":"2015","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","type":"research_data_reference","date_published":"2015-11-06T00:00:00Z","doi":"10.1371/journal.pgen.1005639.s001","citation":{"chicago":"Tugrul, Murat, Tiago Paixao, Nicholas H Barton, and Gašper Tkačik. “Other Fitness Models for Comparison & for Interacting TFBSs.” Public Library of Science, 2015. https://doi.org/10.1371/journal.pgen.1005639.s001.","short":"M. Tugrul, T. Paixao, N.H. Barton, G. Tkačik, (2015).","mla":"Tugrul, Murat, et al. Other Fitness Models for Comparison & for Interacting TFBSs. Public Library of Science, 2015, doi:10.1371/journal.pgen.1005639.s001.","ieee":"M. Tugrul, T. Paixao, N. H. Barton, and G. Tkačik, “Other fitness models for comparison & for interacting TFBSs.” Public Library of Science, 2015.","apa":"Tugrul, M., Paixao, T., Barton, N. H., & Tkačik, G. (2015). Other fitness models for comparison & for interacting TFBSs. Public Library of Science. https://doi.org/10.1371/journal.pgen.1005639.s001","ista":"Tugrul M, Paixao T, Barton NH, Tkačik G. 2015. Other fitness models for comparison & for interacting TFBSs, Public Library of Science, 10.1371/journal.pgen.1005639.s001.","ama":"Tugrul M, Paixao T, Barton NH, Tkačik G. Other fitness models for comparison & for interacting TFBSs. 2015. doi:10.1371/journal.pgen.1005639.s001"},"day":"06","month":"11","article_processing_charge":"No"},{"day":"21","month":"12","article_processing_charge":"No","main_file_link":[{"url":"https://doi.org/10.5061/dryad.cj910","open_access":"1"}],"oa":1,"citation":{"mla":"Wielgoss, Sébastien, et al. Data from: Adaptation to Parasites and Costs of Parasite Resistance in Mutator and Non-Mutator Bacteria. Dryad, 2015, doi:10.5061/dryad.cj910.","short":"S. Wielgoss, T. Bergmiller, A.M. Bischofberger, A.R. Hall, (2015).","chicago":"Wielgoss, Sébastien, Tobias Bergmiller, Anna M. Bischofberger, and Alex R. Hall. “Data from: Adaptation to Parasites and Costs of Parasite Resistance in Mutator and Non-Mutator Bacteria.” Dryad, 2015. https://doi.org/10.5061/dryad.cj910.","ama":"Wielgoss S, Bergmiller T, Bischofberger AM, Hall AR. Data from: Adaptation to parasites and costs of parasite resistance in mutator and non-mutator bacteria. 2015. doi:10.5061/dryad.cj910","ista":"Wielgoss S, Bergmiller T, Bischofberger AM, Hall AR. 2015. Data from: Adaptation to parasites and costs of parasite resistance in mutator and non-mutator bacteria, Dryad, 10.5061/dryad.cj910.","ieee":"S. Wielgoss, T. Bergmiller, A. M. Bischofberger, and A. R. Hall, “Data from: Adaptation to parasites and costs of parasite resistance in mutator and non-mutator bacteria.” Dryad, 2015.","apa":"Wielgoss, S., Bergmiller, T., Bischofberger, A. M., & Hall, A. R. (2015). Data from: Adaptation to parasites and costs of parasite resistance in mutator and non-mutator bacteria. Dryad. https://doi.org/10.5061/dryad.cj910"},"doi":"10.5061/dryad.cj910","date_published":"2015-12-21T00:00:00Z","type":"research_data_reference","abstract":[{"text":"Parasitism creates selection for resistance mechanisms in host populations and is hypothesized to promote increased host evolvability. However, the influence of these traits on host evolution when parasites are no longer present is unclear. We used experimental evolution and whole-genome sequencing of Escherichia coli to determine the effects of past and present exposure to parasitic viruses (phages) on the spread of mutator alleles, resistance, and bacterial competitive fitness. We found that mutator alleles spread rapidly during adaptation to any of four different phage species, and this pattern was even more pronounced with multiple phages present simultaneously. However, hypermutability did not detectably accelerate adaptation in the absence of phages and recovery of fitness costs associated with resistance. Several lineages evolved phage resistance through elevated mucoidy, and during subsequent evolution in phage-free conditions they rapidly reverted to nonmucoid, phage-susceptible phenotypes. Genome sequencing revealed that this phenotypic reversion was achieved by additional genetic changes rather than by genotypic reversion of the initial resistance mutations. Insertion sequence (IS) elements played a key role in both the acquisition of resistance and adaptation in the absence of parasites; unlike single nucleotide polymorphisms, IS insertions were not more frequent in mutator lineages. Our results provide a genetic explanation for rapid reversion of mucoidy, a phenotype observed in other bacterial species including human pathogens. Moreover, this demonstrates that the types of genetic change underlying adaptation to fitness costs, and consequently the impact of evolvability mechanisms such as increased point-mutation rates, depend critically on the mechanism of resistance.","lang":"eng"}],"_id":"9719","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","year":"2015","status":"public","title":"Data from: Adaptation to parasites and costs of parasite resistance in mutator and non-mutator bacteria","publisher":"Dryad","department":[{"_id":"CaGu"}],"author":[{"full_name":"Wielgoss, Sébastien","last_name":"Wielgoss","first_name":"Sébastien"},{"full_name":"Bergmiller, Tobias","last_name":"Bergmiller","first_name":"Tobias","orcid":"0000-0001-5396-4346","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Bischofberger, Anna M.","first_name":"Anna M.","last_name":"Bischofberger"},{"first_name":"Alex R.","last_name":"Hall","full_name":"Hall, Alex R."}],"related_material":{"record":[{"status":"public","relation":"used_in_publication","id":"5749"}]},"date_created":"2021-07-26T08:44:04Z","date_updated":"2023-09-05T13:46:04Z","oa_version":"Published Version"}]