[{"_id":"457","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","title":"Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity","status":"public","intvolume":" 2","oa_version":"None","type":"journal_article","abstract":[{"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","lang":"eng"}],"issue":"2","publication":"Nature Ecology and Evolution","citation":{"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.","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.","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","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","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.","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."},"page":"359 - 366","date_published":"2018-02-01T00:00:00Z","scopus_import":"1","day":"01","article_processing_charge":"No","year":"2018","publication_status":"published","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publisher":"Springer Nature","author":[{"id":"4569785E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7460-7479","first_name":"Maros","last_name":"Pleska","full_name":"Pleska, Maros"},{"id":"29E0800A-F248-11E8-B48F-1D18A9856A87","first_name":"Moritz","last_name":"Lang","full_name":"Lang, Moritz"},{"full_name":"Refardt, Dominik","last_name":"Refardt","first_name":"Dominik"},{"full_name":"Levin, Bruce","first_name":"Bruce","last_name":"Levin"},{"full_name":"Guet, Calin C","last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"}],"related_material":{"record":[{"id":"202","status":"public","relation":"dissertation_contains"}]},"date_created":"2018-12-11T11:46:35Z","date_updated":"2023-09-15T12:04:57Z","volume":2,"ec_funded":1,"publist_id":"7364","external_id":{"isi":["000426516400027"]},"isi":1,"quality_controlled":"1","project":[{"_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734","name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7"},{"_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)"},{"grant_number":"24210","_id":"251D65D8-B435-11E9-9278-68D0E5697425","name":"Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level (DOC Fellowship)"}],"doi":"10.1038/s41559-017-0424-z","language":[{"iso":"eng"}],"month":"02"},{"publication_identifier":{"issn":["2041-1723"]},"month":"12","doi":"10.1038/s41467-018-04342-1","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":["000432280000006"]},"oa":1,"project":[{"_id":"25548C20-B435-11E9-9278-68D0E5697425","grant_number":"303564","name":"Microbial Ion Channels for Synthetic Neurobiology","call_identifier":"FP7"},{"_id":"255A6082-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24","call_identifier":"FWF","name":"Molecular Drug Targets"}],"isi":1,"quality_controlled":"1","ec_funded":1,"file_date_updated":"2020-07-14T12:47:14Z","license":"https://creativecommons.org/licenses/by/4.0/","article_number":"1950","author":[{"id":"4863116E-F248-11E8-B48F-1D18A9856A87","first_name":"Maurizio","last_name":"Morri","full_name":"Morri, Maurizio"},{"full_name":"Sanchez-Romero, Inmaculada","id":"3D9C5D30-F248-11E8-B48F-1D18A9856A87","last_name":"Sanchez-Romero","first_name":"Inmaculada"},{"full_name":"Tichy, Alexandra-Madelaine","first_name":"Alexandra-Madelaine","last_name":"Tichy","id":"29D8BB2C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Kainrath","first_name":"Stephanie","id":"32CFBA64-F248-11E8-B48F-1D18A9856A87","full_name":"Kainrath, Stephanie"},{"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","orcid":"0000-0002-8023-9315","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","last_name":"Janovjak","first_name":"Harald L"}],"volume":9,"date_updated":"2023-09-19T14:29:32Z","date_created":"2019-02-14T10:50:24Z","year":"2018","publisher":"Springer Nature","department":[{"_id":"HaJa"},{"_id":"CaGu"},{"_id":"MiSi"}],"publication_status":"published","has_accepted_license":"1","article_processing_charge":"No","day":"01","scopus_import":"1","date_published":"2018-12-01T00:00:00Z","citation":{"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).","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.","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","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"},"publication":"Nature Communications","issue":"1","abstract":[{"lang":"eng","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."}],"type":"journal_article","file":[{"file_id":"5985","relation":"main_file","date_created":"2019-02-14T10:58:29Z","date_updated":"2020-07-14T12:47:14Z","checksum":"8325fcc194264af4749e662a73bf66b5","file_name":"2018_Springer_Morri.pdf","access_level":"open_access","creator":"kschuh","file_size":1349914,"content_type":"application/pdf"}],"oa_version":"Published Version","_id":"5984","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","intvolume":" 9","title":"Optical functionalization of human class A orphan G-protein-coupled receptors","ddc":["570"],"status":"public"},{"publication_identifier":{"issn":["0737-4038"]},"month":"08","oa":1,"external_id":{"pmid":["30169679"],"isi":["000452567200006"]},"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"}],"publist_id":"8036","pmid":1,"year":"2018","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publisher":"Oxford University Press","publication_status":"published","author":[{"last_name":"Palmer","first_name":"Adam","full_name":"Palmer, Adam"},{"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":"Kishony, Roy","first_name":"Roy","last_name":"Kishony"}],"volume":35,"date_updated":"2023-10-17T11:51:06Z","date_created":"2018-12-11T11:44:11Z","scopus_import":"1","article_processing_charge":"No","day":"28","citation":{"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.","short":"A. Palmer, R.P. Chait, R. Kishony, Molecular Biology and Evolution 35 (2018) 2669–2684.","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.","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","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.","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"},"publication":"Molecular Biology and Evolution","page":"2669 - 2684","article_type":"original","date_published":"2018-08-28T00:00:00Z","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."}],"_id":"19","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":" 35","title":"Nonoptimal gene expression creates latent potential for antibiotic resistance","status":"public","oa_version":"Submitted Version"},{"pubrep_id":"971","oa_version":"Published Version","file":[{"relation":"main_file","file_id":"5151","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","file_size":5027978,"content_type":"application/pdf","creator":"system"}],"_id":"438","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","intvolume":" 46","status":"public","ddc":["576"],"title":"Autoregulation of mazEF expression underlies growth heterogeneity in bacterial populations","issue":"6","abstract":[{"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.","lang":"eng"}],"type":"journal_article","date_published":"2018-04-06T00:00:00Z","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","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.","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","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.","short":"N. Nikolic, T. Bergmiller, A. Vandervelde, T. Albanese, L. Gelens, I. Moll, Nucleic Acids Research 46 (2018) 2918–2931.","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.","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."},"publication":"Nucleic Acids Research","page":"2918-2931","article_processing_charge":"Yes (in subscription journal)","has_accepted_license":"1","day":"06","scopus_import":"1","related_material":{"record":[{"id":"5569","status":"public","relation":"popular_science"}]},"author":[{"full_name":"Nikolic, Nela","first_name":"Nela","last_name":"Nikolic","id":"42D9CABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9068-6090"},{"orcid":"0000-0001-5396-4346","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","last_name":"Bergmiller","first_name":"Tobias","full_name":"Bergmiller, Tobias"},{"first_name":"Alexandra","last_name":"Vandervelde","full_name":"Vandervelde, Alexandra"},{"first_name":"Tanino","last_name":"Albanese","full_name":"Albanese, Tanino"},{"first_name":"Lendert","last_name":"Gelens","full_name":"Gelens, Lendert"},{"full_name":"Moll, Isabella","last_name":"Moll","first_name":"Isabella"}],"volume":46,"date_updated":"2024-02-21T13:44:45Z","date_created":"2018-12-11T11:46:29Z","year":"2018","department":[{"_id":"CaGu"}],"publisher":"Oxford University Press","publication_status":"published","file_date_updated":"2020-07-14T12:46:27Z","doi":"10.1093/nar/gky079","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":["000429009500021"]},"oa":1,"project":[{"_id":"3AC91DDA-15DF-11EA-824D-93A3E7B544D1","call_identifier":"FWF","name":"FWF Open Access Fund"}],"isi":1,"quality_controlled":"1","month":"04"},{"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.","mla":"Bergmiller, Tobias, and Nela Nikolic. Time-Lapse Microscopy Data. Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:74.","short":"T. Bergmiller, N. Nikolic, (2018).","ista":"Bergmiller T, Nikolic N. 2018. Time-lapse microscopy data, Institute of Science and Technology Austria, 10.15479/AT:ISTA:74.","apa":"Bergmiller, T., & Nikolic, N. (2018). Time-lapse microscopy data. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:74","ieee":"T. Bergmiller and N. Nikolic, “Time-lapse microscopy data.” Institute of Science and Technology Austria, 2018.","ama":"Bergmiller T, Nikolic N. Time-lapse microscopy data. 2018. doi:10.15479/AT:ISTA:74"},"date_published":"2018-02-07T00:00:00Z","doi":"10.15479/AT:ISTA:74","keyword":["microscopy","microfluidics"],"has_accepted_license":"1","article_processing_charge":"No","day":"07","month":"02","_id":"5569","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","year":"2018","publisher":"Institute of Science and Technology Austria","department":[{"_id":"CaGu"}],"status":"public","ddc":["579"],"title":"Time-lapse microscopy data","related_material":{"record":[{"id":"438","status":"public","relation":"research_paper"}]},"author":[{"first_name":"Tobias","last_name":"Bergmiller","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5396-4346","full_name":"Bergmiller, Tobias"},{"id":"42D9CABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9068-6090","first_name":"Nela","last_name":"Nikolic","full_name":"Nikolic, Nela"}],"oa_version":"Published Version","file":[{"file_id":"5637","relation":"main_file","date_updated":"2020-07-14T12:47:04Z","date_created":"2018-12-12T13:04:39Z","checksum":"61ebb92213cfffeba3ddbaff984b81af","file_name":"IST-2018-74-v1+2_15-11-05.zip","access_level":"open_access","creator":"system","content_type":"application/zip","file_size":3558703796},{"file_id":"5638","relation":"main_file","checksum":"bf26649af310ef6892d68576515cde6d","date_updated":"2020-07-14T12:47:04Z","date_created":"2018-12-12T13:04:55Z","access_level":"open_access","file_name":"IST-2018-74-v1+3_15-07-31.zip","creator":"system","content_type":"application/zip","file_size":1830422606},{"file_id":"5639","relation":"main_file","checksum":"8e46eedce06f22acb2be1a9b9d3f56bd","date_created":"2018-12-12T13:05:11Z","date_updated":"2020-07-14T12:47:04Z","access_level":"open_access","file_name":"IST-2018-74-v1+4_Images_for_analysis.zip","creator":"system","file_size":2140849248,"content_type":"application/zip"}],"date_updated":"2024-02-21T13:44:45Z","date_created":"2018-12-12T12:31:35Z","type":"research_data","datarep_id":"74","publist_id":"7385","file_date_updated":"2020-07-14T12:47:04Z","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"}],"license":"https://creativecommons.org/publicdomain/zero/1.0/"},{"related_material":{"record":[{"relation":"popular_science","status":"public","id":"5587"}]},"author":[{"full_name":"De Martino, Daniele","first_name":"Daniele","last_name":"De Martino","id":"3FF5848A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-5214-4706"},{"first_name":"Andersson Anna","last_name":"Mc","full_name":"Mc, Andersson Anna"},{"first_name":"Tobias","last_name":"Bergmiller","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5396-4346","full_name":"Bergmiller, Tobias"},{"orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C","full_name":"Guet, Calin C"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","first_name":"Gasper","last_name":"Tkacik","full_name":"Tkacik, Gasper"}],"volume":9,"date_updated":"2024-02-21T13:45:39Z","date_created":"2018-12-11T11:44:57Z","year":"2018","department":[{"_id":"GaTk"},{"_id":"CaGu"}],"publisher":"Springer Nature","publication_status":"published","ec_funded":1,"publist_id":"7760","file_date_updated":"2020-07-14T12:45:06Z","article_number":"2988","doi":"10.1038/s41467-018-05417-9","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":["000440149300021"]},"project":[{"name":"Biophysics of information processing in gene regulation","call_identifier":"FWF","_id":"254E9036-B435-11E9-9278-68D0E5697425","grant_number":"P28844-B27"},{"call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734"}],"isi":1,"quality_controlled":"1","month":"07","file":[{"relation":"main_file","file_id":"5728","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","content_type":"application/pdf","file_size":1043205,"creator":"dernst"}],"oa_version":"Published Version","_id":"161","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","intvolume":" 9","status":"public","title":"Statistical mechanics for metabolic networks during steady state growth","ddc":["570"],"issue":"1","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."}],"type":"journal_article","date_published":"2018-07-30T00:00:00Z","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.","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.","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","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)."},"publication":"Nature Communications","has_accepted_license":"1","article_processing_charge":"No","day":"30","scopus_import":"1"},{"day":"30","article_processing_charge":"No","has_accepted_license":"1","page":"109","citation":{"short":"M. Steinrück, The Influence of Sequence Context on the Evolution of Bacterial Gene Expression, Institute of Science and Technology Austria, 2018.","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.","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","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","ieee":"M. Steinrück, “The influence of sequence context on the evolution of bacterial gene expression,” Institute of Science and Technology Austria, 2018.","ista":"Steinrück M. 2018. The influence of sequence context on the evolution of bacterial gene expression. Institute of Science and Technology Austria."},"date_published":"2018-10-30T00:00:00Z","alternative_title":["ISTA Thesis"],"type":"dissertation","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"}],"title":"The influence of sequence context on the evolution of bacterial gene expression","ddc":["576","579"],"status":"public","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"26","file":[{"file_name":"Thesis_Steinrueck_final.docx","embargo_to":"open_access","access_level":"closed","creator":"dernst","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_size":9190845,"file_id":"5941","relation":"source_file","date_updated":"2020-07-14T12:45:43Z","date_created":"2019-02-08T10:51:22Z","checksum":"413cbce1cd1debeae3abe2a25dbc70d1"},{"file_size":7521973,"content_type":"application/pdf","creator":"dernst","access_level":"open_access","file_name":"Thesis_Steinrueck_final.pdf","checksum":"3def8b7854c8b42d643597ce0215efac","date_created":"2019-02-08T10:51:22Z","date_updated":"2021-02-11T11:17:14Z","relation":"main_file","file_id":"5942","embargo":"2019-11-02"}],"oa_version":"Published Version","pubrep_id":"1059","month":"10","publication_identifier":{"issn":["2663-337X"]},"oa":1,"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:th1059","file_date_updated":"2021-02-11T11:17:14Z","publist_id":"8029","publication_status":"published","department":[{"_id":"CaGu"}],"publisher":"Institute of Science and Technology Austria","year":"2018","date_created":"2018-12-11T11:44:14Z","date_updated":"2023-09-07T12:48:43Z","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"}]}},{"ec_funded":1,"publist_id":"7987","file_date_updated":"2020-07-14T12:47:37Z","related_material":{"record":[{"id":"5585","relation":"popular_science","status":"public"},{"id":"6371","status":"public","relation":"dissertation_contains"}]},"author":[{"first_name":"Claudia","last_name":"Igler","id":"46613666-F248-11E8-B48F-1D18A9856A87","full_name":"Igler, Claudia"},{"full_name":"Lagator, Mato","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","last_name":"Lagator","first_name":"Mato"},{"full_name":"Tkacik, Gasper","last_name":"Tkacik","first_name":"Gasper","orcid":"0000-0002-6699-1455","id":"3D494DCA-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"},{"full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet"}],"volume":2,"date_updated":"2024-03-28T23:30:49Z","date_created":"2018-12-11T11:44:27Z","year":"2018","publisher":"Nature Publishing Group","department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"JoBo"}],"publication_status":"published","month":"09","doi":"10.1038/s41559-018-0651-y","language":[{"iso":"eng"}],"external_id":{"isi":["000447947600021"]},"oa":1,"project":[{"name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734"},{"call_identifier":"H2020","name":"Selective Barriers to Horizontal Gene Transfer","grant_number":"648440","_id":"2578D616-B435-11E9-9278-68D0E5697425"},{"name":"Design principles underlying genetic switch architecture (DOC Fellowship)","grant_number":"24573","_id":"251EE76E-B435-11E9-9278-68D0E5697425"}],"isi":1,"quality_controlled":"1","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"}],"type":"journal_article","oa_version":"Submitted Version","file":[{"file_size":1135973,"content_type":"application/pdf","creator":"dernst","file_name":"2018_NatureEcology_Igler.pdf","access_level":"open_access","date_created":"2020-05-14T11:28:52Z","date_updated":"2020-07-14T12:47:37Z","checksum":"383a2e2c944a856e2e821ec8e7bf71b6","relation":"main_file","file_id":"7830"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"67","intvolume":" 2","title":"Evolutionary potential of transcription factors for gene regulatory rewiring","ddc":["570"],"status":"public","has_accepted_license":"1","article_processing_charge":"No","day":"10","scopus_import":"1","date_published":"2018-09-10T00:00:00Z","citation":{"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.","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","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.","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","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.","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."},"publication":"Nature Ecology and Evolution","page":"1633 - 1643","article_type":"original"},{"has_accepted_license":"1","article_processing_charge":"No","month":"07","day":"20","date_published":"2018-07-20T00:00:00Z","doi":"10.15479/AT:ISTA:108","project":[{"call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734"},{"_id":"2578D616-B435-11E9-9278-68D0E5697425","grant_number":"648440","name":"Selective Barriers to Horizontal Gene Transfer","call_identifier":"H2020"},{"grant_number":"24573","_id":"251EE76E-B435-11E9-9278-68D0E5697425","name":"Design principles underlying genetic switch architecture (DOC Fellowship)"}],"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":{"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.","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","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.","ama":"Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. 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Guet, (2018)."},"ec_funded":1,"abstract":[{"lang":"eng","text":"Mean repression values and standard error of the mean are given for all operator mutant libraries."}],"file_date_updated":"2020-07-14T12:47:07Z","type":"research_data","datarep_id":"108","file":[{"access_level":"open_access","file_name":"IST-2018-108-v1+1_data_figures.xlsx","creator":"system","file_size":16507,"content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","file_id":"5611","relation":"main_file","checksum":"1435781526c77413802adee0d4583cce","date_updated":"2020-07-14T12:47:07Z","date_created":"2018-12-12T13:02:45Z"}],"oa_version":"Published Version","date_created":"2018-12-12T12:31:40Z","date_updated":"2024-03-28T23:30:49Z","related_material":{"record":[{"id":"67","relation":"research_paper","status":"public"},{"relation":"research_paper","status":"public","id":"6371"}]},"author":[{"last_name":"Igler","first_name":"Claudia","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","last_name":"Tkacik","first_name":"Gasper","orcid":"0000-0002-6699-1455","id":"3D494DCA-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"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet","full_name":"Guet, Calin C"}],"department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publisher":"Institute of Science and Technology Austria","ddc":["576"],"status":"public","title":"Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring","_id":"5585","year":"2018","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"},{"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":[{"call_identifier":"FP7","name":"Microbial Ion Channels for Synthetic Neurobiology","grant_number":"303564","_id":"25548C20-B435-11E9-9278-68D0E5697425"},{"grant_number":"W1232-B24","_id":"255A6082-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Molecular Drug Targets"}],"doi":"10.1002/ange.201611998","language":[{"iso":"eng"}],"month":"05","year":"2017","publication_status":"published","department":[{"_id":"CaGu"},{"_id":"HaJa"}],"publisher":"Wiley","author":[{"first_name":"Stephanie","last_name":"Kainrath","id":"32CFBA64-F248-11E8-B48F-1D18A9856A87","full_name":"Kainrath, Stephanie"},{"full_name":"Stadler, Manuela","last_name":"Stadler","first_name":"Manuela"},{"last_name":"Gschaider-Reichhart","first_name":"Eva","orcid":"0000-0002-7218-7738","id":"3FEE232A-F248-11E8-B48F-1D18A9856A87","full_name":"Gschaider-Reichhart, Eva"},{"last_name":"Distel","first_name":"Martin","full_name":"Distel, Martin"},{"id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8023-9315","first_name":"Harald L","last_name":"Janovjak","full_name":"Janovjak, Harald L"}],"date_updated":"2021-01-12T08:01:33Z","date_created":"2018-12-11T11:47:02Z","volume":129,"file_date_updated":"2020-07-14T12:46:39Z","ec_funded":1,"publist_id":"7279","publication":"Angewandte Chemie","citation":{"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.","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","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.","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."},"page":"4679 - 4682","date_published":"2017-05-20T00:00:00Z","day":"20","has_accepted_license":"1","_id":"538","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","title":"Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen","ddc":["571"],"intvolume":" 129","pubrep_id":"932","oa_version":"Published Version","file":[{"content_type":"application/pdf","file_size":1668557,"creator":"system","file_name":"IST-2018-932-v1+1_Kainrath_et_al-2017-Angewandte_Chemie.pdf","access_level":"open_access","date_updated":"2020-07-14T12:46:39Z","date_created":"2018-12-12T10:13:24Z","checksum":"d66fee867e7cdbfa3fe276c2fb0778bb","relation":"main_file","file_id":"5007"}],"type":"journal_article","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"},{"title":"Regulatory network structure determines patterns of intermolecular epistasis","status":"public","ddc":["576"],"intvolume":" 6","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"570","oa_version":"Published Version","file":[{"checksum":"273ab17f33305e4eaafd911ff88e7c5b","date_created":"2018-12-12T10:14:42Z","date_updated":"2020-07-14T12:47:10Z","relation":"main_file","file_id":"5096","file_size":8453470,"content_type":"application/pdf","creator":"system","access_level":"open_access","file_name":"IST-2017-918-v1+1_elife-28921-figures-v3.pdf"},{"file_name":"IST-2017-918-v1+2_elife-28921-v3.pdf","access_level":"open_access","creator":"system","content_type":"application/pdf","file_size":1953221,"file_id":"5097","relation":"main_file","date_created":"2018-12-12T10:14:43Z","date_updated":"2020-07-14T12:47:10Z","checksum":"b433f90576c7be597cd43367946f8e7f"}],"pubrep_id":"918","type":"journal_article","abstract":[{"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. ","lang":"eng"}],"publication":"eLife","citation":{"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.","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).","ista":"Lagator M, Sarikas S, Acar H, Bollback JP, Guet CC. 2017. Regulatory network structure determines patterns of intermolecular epistasis. eLife. 6, e28921.","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.","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","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"},"date_published":"2017-11-13T00:00:00Z","scopus_import":1,"day":"13","has_accepted_license":"1","publication_status":"published","publisher":"eLife Sciences Publications","department":[{"_id":"CaGu"},{"_id":"JoBo"},{"_id":"NiBa"}],"year":"2017","date_updated":"2021-01-12T08:03:15Z","date_created":"2018-12-11T11:47:14Z","volume":6,"author":[{"first_name":"Mato","last_name":"Lagator","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","full_name":"Lagator, Mato"},{"full_name":"Sarikas, Srdjan","first_name":"Srdjan","last_name":"Sarikas","id":"35F0286E-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-1986-9753","id":"2DDF136A-F248-11E8-B48F-1D18A9856A87","last_name":"Acar","first_name":"Hande","full_name":"Acar, Hande"},{"full_name":"Bollback, Jonathan P","last_name":"Bollback","first_name":"Jonathan P","orcid":"0000-0002-4624-4612","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C"}],"article_number":"e28921","file_date_updated":"2020-07-14T12:47:10Z","publist_id":"7244","ec_funded":1,"quality_controlled":"1","project":[{"_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734","name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7"},{"call_identifier":"H2020","name":"Selective Barriers to Horizontal Gene Transfer","grant_number":"648440","_id":"2578D616-B435-11E9-9278-68D0E5697425"}],"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":"10.7554/eLife.28921","month":"11","publication_identifier":{"issn":["2050084X"]}},{"oa_version":"Published Version","file":[{"file_size":1951699,"content_type":"application/pdf","creator":"system","access_level":"open_access","file_name":"IST-2017-911-v1+1_s41467-017-01683-1.pdf","checksum":"44bb5d0229926c23a9955d9fe0f9723f","date_created":"2018-12-12T10:16:05Z","date_updated":"2020-07-14T12:47:20Z","relation":"main_file","file_id":"5190"}],"pubrep_id":"911","status":"public","ddc":["576","579"],"title":"Shaping bacterial population behavior through computer interfaced control of individual cells","intvolume":" 8","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","_id":"613","abstract":[{"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.","lang":"eng"}],"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,"date_updated":"2021-01-12T08:06:15Z","date_created":"2018-12-11T11:47:30Z","volume":8,"author":[{"full_name":"Chait, Remy P","orcid":"0000-0003-0876-3187","id":"3464AE84-F248-11E8-B48F-1D18A9856A87","last_name":"Chait","first_name":"Remy P"},{"id":"4A245D00-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1615-3282","first_name":"Jakob","last_name":"Ruess","full_name":"Ruess, Jakob"},{"orcid":"0000-0001-5396-4346","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","last_name":"Bergmiller","first_name":"Tobias","full_name":"Bergmiller, Tobias"},{"last_name":"Tkacik","first_name":"Gasper","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkacik, Gasper"},{"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","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publisher":"Nature Publishing Group","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","publist_id":"7191","ec_funded":1,"article_number":"1535","language":[{"iso":"eng"}],"doi":"10.1038/s41467-017-01683-1","quality_controlled":"1","project":[{"grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme"},{"_id":"254E9036-B435-11E9-9278-68D0E5697425","grant_number":"P28844-B27","name":"Biophysics of information processing in gene regulation","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"},"oa":1,"month":"12","publication_identifier":{"issn":["20411723"]}},{"issue":"9","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."}],"type":"journal_article","pubrep_id":"909","file":[{"content_type":"application/pdf","file_size":682064,"creator":"system","access_level":"open_access","file_name":"IST-2017-909-v1+1_peerj-3830.pdf","checksum":"3d79ae6b6eabc90b0eaaed82ff3493b0","date_created":"2018-12-12T10:11:51Z","date_updated":"2020-07-14T12:47:24Z","relation":"main_file","file_id":"4908"}],"oa_version":"Published Version","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"624","intvolume":" 2017","title":"MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations","ddc":["579"],"status":"public","has_accepted_license":"1","day":"21","scopus_import":1,"date_published":"2017-09-21T00:00:00Z","citation":{"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","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.","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","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.","short":"N. Nikolic, Z. Didara, I. Moll, PeerJ 2017 (2017).","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.","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."},"publication":"PeerJ","publist_id":"7172","file_date_updated":"2020-07-14T12:47:24Z","article_number":"3830","author":[{"full_name":"Nikolic, Nela","orcid":"0000-0001-9068-6090","id":"42D9CABC-F248-11E8-B48F-1D18A9856A87","last_name":"Nikolic","first_name":"Nela"},{"full_name":"Didara, Zrinka","last_name":"Didara","first_name":"Zrinka"},{"first_name":"Isabella","last_name":"Moll","full_name":"Moll, Isabella"}],"volume":2017,"date_updated":"2021-01-12T08:06:48Z","date_created":"2018-12-11T11:47:33Z","acknowledgement":"Austrian Science Fund (FWF): M1697, P22249; Swiss National Science Foundation (SNF): 145706; European Commission;FWF Special Research Program: RNA-REG F43","year":"2017","publisher":"PeerJ","department":[{"_id":"CaGu"}],"publication_status":"published","publication_identifier":{"issn":["21678359"]},"month":"09","doi":"10.7717/peerj.3830","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"},"quality_controlled":"1"},{"_id":"655","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Bacterial flagella grow through an injection diffusion mechanism","status":"public","ddc":["579"],"intvolume":" 6","pubrep_id":"904","file":[{"file_name":"IST-2017-904-v1+1_elife-23136-v2.pdf","access_level":"open_access","creator":"system","content_type":"application/pdf","file_size":5520359,"file_id":"4716","relation":"main_file","date_updated":"2020-07-14T12:47:33Z","date_created":"2018-12-12T10:08:53Z","checksum":"39e1c3e82ddac83a30422fa72fa1a383"},{"relation":"main_file","file_id":"4717","date_created":"2018-12-12T10:08:54Z","date_updated":"2020-07-14T12:47:33Z","checksum":"a6d542253028f52e00aa29739ddffe8f","file_name":"IST-2017-904-v1+2_elife-23136-figures-v2.pdf","access_level":"open_access","file_size":11242920,"content_type":"application/pdf","creator":"system"}],"oa_version":"Published Version","type":"journal_article","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"}],"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.","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).","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.","ieee":"T. Renault et al., “Bacterial flagella grow through an injection diffusion mechanism,” eLife, vol. 6. eLife Sciences Publications, 2017.","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","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.","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"},"date_published":"2017-03-06T00:00:00Z","scopus_import":1,"day":"06","has_accepted_license":"1","year":"2017","publication_status":"published","department":[{"_id":"CaGu"}],"publisher":"eLife Sciences Publications","author":[{"full_name":"Renault, Thibaud","last_name":"Renault","first_name":"Thibaud"},{"full_name":"Abraham, Anthony","first_name":"Anthony","last_name":"Abraham"},{"full_name":"Bergmiller, Tobias","first_name":"Tobias","last_name":"Bergmiller","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5396-4346"},{"first_name":"Guillaume","last_name":"Paradis","full_name":"Paradis, Guillaume"},{"last_name":"Rainville","first_name":"Simon","full_name":"Rainville, Simon"},{"full_name":"Charpentier, Emmanuelle","last_name":"Charpentier","first_name":"Emmanuelle"},{"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":"Yuhai","last_name":"Tu","full_name":"Tu, Yuhai"},{"full_name":"Namba, Keiichi","last_name":"Namba","first_name":"Keiichi"},{"first_name":"James","last_name":"Keener","full_name":"Keener, James"},{"full_name":"Minamino, Tohru","last_name":"Minamino","first_name":"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,"article_number":"e23136","file_date_updated":"2020-07-14T12:47:33Z","publist_id":"7082","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.23136","language":[{"iso":"eng"}],"month":"03","publication_identifier":{"issn":["2050084X"]}},{"year":"2017","department":[{"_id":"CaGu"}],"publisher":"Public Library of Science","publication_status":"published","related_material":{"record":[{"id":"9844","status":"public","relation":"research_data"},{"id":"9845","status":"public","relation":"research_data"},{"relation":"research_data","status":"public","id":"9846"}]},"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","last_name":"Schreiber","first_name":"Frank"},{"full_name":"Dal Co, Alma","first_name":"Alma","last_name":"Dal Co"},{"last_name":"Kiviet","first_name":"Daniel","full_name":"Kiviet, Daniel"},{"id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5396-4346","first_name":"Tobias","last_name":"Bergmiller","full_name":"Bergmiller, Tobias"},{"full_name":"Littmann, Sten","first_name":"Sten","last_name":"Littmann"},{"full_name":"Kuypers, Marcel","last_name":"Kuypers","first_name":"Marcel"},{"full_name":"Ackermann, Martin","first_name":"Martin","last_name":"Ackermann"}],"volume":13,"date_updated":"2023-02-23T14:10:34Z","date_created":"2018-12-11T11:47:04Z","article_number":"e1007122","publist_id":"7275","ec_funded":1,"file_date_updated":"2020-07-14T12:46:46Z","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":[{"_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734","name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7"}],"quality_controlled":"1","doi":"10.1371/journal.pgen.1007122","language":[{"iso":"eng"}],"publication_identifier":{"issn":["15537390"]},"month":"12","_id":"541","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":" 13","title":"Cell-to-cell variation and specialization in sugar metabolism in clonal bacterial populations","ddc":["576","579"],"status":"public","pubrep_id":"959","file":[{"date_created":"2018-12-12T10:14:35Z","date_updated":"2020-07-14T12:46:46Z","checksum":"22426d9382f21554bad5fa5967afcfd0","relation":"main_file","file_id":"5088","content_type":"application/pdf","file_size":1308475,"creator":"system","file_name":"IST-2018-959-v1+1_2017_Nikolic_Cell-to-cell.pdf","access_level":"open_access"}],"oa_version":"Published Version","type":"journal_article","issue":"12","abstract":[{"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.","lang":"eng"}],"citation":{"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.","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"},"publication":"PLoS Genetics","date_published":"2017-12-18T00:00:00Z","scopus_import":1,"has_accepted_license":"1","day":"18"},{"citation":{"chicago":"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.” The Royal Society, 2017. https://doi.org/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. The Royal Society, 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.","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"},"main_file_link":[{"open_access":"1","url":"https://doi.org/10.6084/m9.figshare.5633917.v1"}],"oa":1,"date_published":"2017-11-27T00:00:00Z","doi":"10.6084/m9.figshare.5633917.v1","month":"11","day":"27","article_processing_charge":"No","status":"public","title":"Supplementary materials and methods; Full data set from effects of mutations in phage restriction sites during escape from restriction–modification","publisher":"The Royal Society","department":[{"_id":"CaGu"}],"user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","_id":"9847","year":"2017","date_created":"2021-08-09T13:54:38Z","date_updated":"2023-02-23T12:29:44Z","oa_version":"Published Version","author":[{"full_name":"Pleska, Maros","id":"4569785E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7460-7479","first_name":"Maros","last_name":"Pleska"},{"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":"561","status":"public","relation":"used_in_publication"}]},"type":"research_data_reference","abstract":[{"text":"information on culture conditions, phage mutagenesis, verification and lysate preparation; Raw data","lang":"eng"}]},{"month":"12","day":"18","article_processing_charge":"No","citation":{"ama":"Nikolic N, Schreiber F, Dal Co A, et al. Mathematical model. 2017. doi:10.1371/journal.pgen.1007122.s017","ista":"Nikolic N, Schreiber F, Dal Co A, Kiviet D, Bergmiller T, Littmann S, Kuypers M, Ackermann M. 2017. Mathematical model, Public Library of Science, 10.1371/journal.pgen.1007122.s017.","apa":"Nikolic, N., Schreiber, F., Dal Co, A., Kiviet, D., Bergmiller, T., Littmann, S., … Ackermann, M. (2017). Mathematical model. Public Library of Science. https://doi.org/10.1371/journal.pgen.1007122.s017","ieee":"N. Nikolic et al., “Mathematical model.” Public Library of Science, 2017.","mla":"Nikolic, Nela, et al. Mathematical Model. Public Library of Science, 2017, doi:10.1371/journal.pgen.1007122.s017.","short":"N. Nikolic, F. Schreiber, A. Dal Co, D. Kiviet, T. Bergmiller, S. Littmann, M. Kuypers, M. Ackermann, (2017).","chicago":"Nikolic, Nela, Frank Schreiber, Alma Dal Co, Daniel Kiviet, Tobias Bergmiller, Sten Littmann, Marcel Kuypers, and Martin Ackermann. “Mathematical Model.” Public Library of Science, 2017. https://doi.org/10.1371/journal.pgen.1007122.s017."},"date_published":"2017-12-18T00:00:00Z","doi":"10.1371/journal.pgen.1007122.s017","type":"research_data_reference","abstract":[{"lang":"eng","text":"Estimates of 13 C-arabinose and 2 H-glucose uptake from the fractions of heavy isotopes measured\tin single cells"}],"year":"2017","_id":"9845","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","title":"Mathematical model","status":"public","department":[{"_id":"CaGu"}],"publisher":"Public Library of Science","author":[{"first_name":"Nela","last_name":"Nikolic","id":"42D9CABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9068-6090","full_name":"Nikolic, Nela"},{"full_name":"Schreiber, Frank","last_name":"Schreiber","first_name":"Frank"},{"first_name":"Alma","last_name":"Dal Co","full_name":"Dal Co, Alma"},{"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"},{"full_name":"Ackermann, Martin","first_name":"Martin","last_name":"Ackermann"}],"related_material":{"record":[{"status":"public","relation":"used_in_publication","id":"541"}]},"date_updated":"2023-02-23T12:25:04Z","date_created":"2021-08-09T13:31:51Z","oa_version":"None"},{"day":"18","month":"07","article_processing_charge":"No","doi":"10.1371/journal.pcbi.1005609.s001","date_published":"2017-07-18T00:00:00Z","citation":{"ista":"Lukacisinova M, Novak S, Paixao T. 2017. Modelling and simulation details, Public Library of Science, 10.1371/journal.pcbi.1005609.s001.","ieee":"M. Lukacisinova, S. Novak, and T. Paixao, “Modelling and simulation details.” Public Library of Science, 2017.","apa":"Lukacisinova, M., Novak, S., & Paixao, T. (2017). Modelling and simulation details. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1005609.s001","ama":"Lukacisinova M, Novak S, Paixao T. Modelling and simulation details. 2017. doi:10.1371/journal.pcbi.1005609.s001","chicago":"Lukacisinova, Marta, Sebastian Novak, and Tiago Paixao. “Modelling and Simulation Details.” Public Library of Science, 2017. https://doi.org/10.1371/journal.pcbi.1005609.s001.","mla":"Lukacisinova, Marta, et al. Modelling and Simulation Details. Public Library of Science, 2017, doi:10.1371/journal.pcbi.1005609.s001.","short":"M. Lukacisinova, S. Novak, T. Paixao, (2017)."},"abstract":[{"lang":"eng","text":"This text provides additional information about the model, a derivation of the analytic results in Eq (4), and details about simulations of an additional parameter set."}],"type":"research_data_reference","date_created":"2021-08-09T14:02:34Z","date_updated":"2023-02-23T12:55:39Z","oa_version":"Published Version","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","id":"461468AE-F248-11E8-B48F-1D18A9856A87","first_name":"Sebastian","last_name":"Novak"},{"full_name":"Paixao, Tiago","first_name":"Tiago","last_name":"Paixao","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2361-3953"}],"related_material":{"record":[{"id":"696","status":"public","relation":"used_in_publication"}]},"title":"Modelling and simulation details","status":"public","department":[{"_id":"ToBo"},{"_id":"NiBa"},{"_id":"CaGu"}],"publisher":"Public Library of Science","year":"2017","_id":"9849","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf"},{"article_processing_charge":"No","day":"18","month":"07","doi":"10.1371/journal.pcbi.1005609.s002","date_published":"2017-07-18T00:00:00Z","citation":{"ama":"Lukacisinova M, Novak S, Paixao T. Extensions of the model. 2017. doi:10.1371/journal.pcbi.1005609.s002","ista":"Lukacisinova M, Novak S, Paixao T. 2017. Extensions of the model, Public Library of Science, 10.1371/journal.pcbi.1005609.s002.","apa":"Lukacisinova, M., Novak, S., & Paixao, T. (2017). Extensions of the model. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1005609.s002","ieee":"M. Lukacisinova, S. Novak, and T. Paixao, “Extensions of the model.” Public Library of Science, 2017.","mla":"Lukacisinova, Marta, et al. Extensions of the Model. Public Library of Science, 2017, doi:10.1371/journal.pcbi.1005609.s002.","short":"M. Lukacisinova, S. Novak, T. Paixao, (2017).","chicago":"Lukacisinova, Marta, Sebastian Novak, and Tiago Paixao. “Extensions of the Model.” Public Library of Science, 2017. https://doi.org/10.1371/journal.pcbi.1005609.s002."},"abstract":[{"text":"In this text, we discuss how a cost of resistance and the possibility of lethal mutations impact our model.","lang":"eng"}],"type":"research_data_reference","related_material":{"record":[{"id":"696","relation":"used_in_publication","status":"public"}]},"author":[{"full_name":"Lukacisinova, Marta","first_name":"Marta","last_name":"Lukacisinova","id":"4342E402-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2519-8004"},{"id":"461468AE-F248-11E8-B48F-1D18A9856A87","first_name":"Sebastian","last_name":"Novak","full_name":"Novak, Sebastian"},{"orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","last_name":"Paixao","first_name":"Tiago","full_name":"Paixao, Tiago"}],"oa_version":"Published Version","date_updated":"2023-02-23T12:55:39Z","date_created":"2021-08-09T14:05:24Z","year":"2017","_id":"9850","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","publisher":"Public Library of Science","department":[{"_id":"ToBo"},{"_id":"CaGu"},{"_id":"NiBa"}],"status":"public","title":"Extensions of the model"},{"department":[{"_id":"CaGu"}],"publisher":"Public Library of Science","title":"Supplementary methods","status":"public","_id":"9846","year":"2017","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","oa_version":"Published Version","date_updated":"2023-02-23T12:25:04Z","date_created":"2021-08-09T13:35:17Z","related_material":{"record":[{"id":"541","relation":"used_in_publication","status":"public"}]},"author":[{"first_name":"Nela","last_name":"Nikolic","id":"42D9CABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9068-6090","full_name":"Nikolic, Nela"},{"first_name":"Frank","last_name":"Schreiber","full_name":"Schreiber, Frank"},{"first_name":"Alma","last_name":"Dal Co","full_name":"Dal Co, Alma"},{"first_name":"Daniel","last_name":"Kiviet","full_name":"Kiviet, Daniel"},{"id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5396-4346","first_name":"Tobias","last_name":"Bergmiller","full_name":"Bergmiller, Tobias"},{"full_name":"Littmann, Sten","first_name":"Sten","last_name":"Littmann"},{"full_name":"Kuypers, Marcel","last_name":"Kuypers","first_name":"Marcel"},{"last_name":"Ackermann","first_name":"Martin","full_name":"Ackermann, Martin"}],"type":"research_data_reference","citation":{"chicago":"Nikolic, Nela, Frank Schreiber, Alma Dal Co, Daniel Kiviet, Tobias Bergmiller, Sten Littmann, Marcel Kuypers, and Martin Ackermann. “Supplementary Methods.” Public Library of Science, 2017. https://doi.org/10.1371/journal.pgen.1007122.s016.","mla":"Nikolic, Nela, et al. Supplementary Methods. Public Library of Science, 2017, doi:10.1371/journal.pgen.1007122.s016.","short":"N. Nikolic, F. Schreiber, A. Dal Co, D. Kiviet, T. Bergmiller, S. Littmann, M. Kuypers, M. Ackermann, (2017).","ista":"Nikolic N, Schreiber F, Dal Co A, Kiviet D, Bergmiller T, Littmann S, Kuypers M, Ackermann M. 2017. Supplementary methods, Public Library of Science, 10.1371/journal.pgen.1007122.s016.","ieee":"N. Nikolic et al., “Supplementary methods.” Public Library of Science, 2017.","apa":"Nikolic, N., Schreiber, F., Dal Co, A., Kiviet, D., Bergmiller, T., Littmann, S., … Ackermann, M. (2017). Supplementary methods. Public Library of Science. https://doi.org/10.1371/journal.pgen.1007122.s016","ama":"Nikolic N, Schreiber F, Dal Co A, et al. Supplementary methods. 2017. doi:10.1371/journal.pgen.1007122.s016"},"date_published":"2017-12-18T00:00:00Z","doi":"10.1371/journal.pgen.1007122.s016","article_processing_charge":"No","day":"18","month":"12"},{"abstract":[{"lang":"eng","text":"Based on the intuitive derivation of the dynamics of SIM allele frequency pM in the main text, we present a heuristic prediction for the long-term SIM allele frequencies with χ > 1 stresses and compare it to numerical simulations."}],"type":"research_data_reference","author":[{"full_name":"Lukacisinova, Marta","last_name":"Lukacisinova","first_name":"Marta","orcid":"0000-0002-2519-8004","id":"4342E402-F248-11E8-B48F-1D18A9856A87"},{"id":"461468AE-F248-11E8-B48F-1D18A9856A87","last_name":"Novak","first_name":"Sebastian","full_name":"Novak, Sebastian"},{"last_name":"Paixao","first_name":"Tiago","orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","full_name":"Paixao, Tiago"}],"related_material":{"record":[{"status":"public","relation":"used_in_publication","id":"696"}]},"date_created":"2021-08-09T14:08:14Z","date_updated":"2023-02-23T12:55:39Z","oa_version":"Published Version","_id":"9851","year":"2017","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","title":"Heuristic prediction for multiple stresses","status":"public","publisher":"Public Library of Science","department":[{"_id":"ToBo"},{"_id":"CaGu"},{"_id":"NiBa"}],"day":"18","month":"07","article_processing_charge":"No","doi":"10.1371/journal.pcbi.1005609.s003","date_published":"2017-07-18T00:00:00Z","citation":{"ama":"Lukacisinova M, Novak S, Paixao T. Heuristic prediction for multiple stresses. 2017. doi:10.1371/journal.pcbi.1005609.s003","ista":"Lukacisinova M, Novak S, Paixao T. 2017. Heuristic prediction for multiple stresses, Public Library of Science, 10.1371/journal.pcbi.1005609.s003.","apa":"Lukacisinova, M., Novak, S., & Paixao, T. (2017). Heuristic prediction for multiple stresses. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1005609.s003","ieee":"M. Lukacisinova, S. Novak, and T. Paixao, “Heuristic prediction for multiple stresses.” Public Library of Science, 2017.","mla":"Lukacisinova, Marta, et al. Heuristic Prediction for Multiple Stresses. Public Library of Science, 2017, doi:10.1371/journal.pcbi.1005609.s003.","short":"M. Lukacisinova, S. Novak, T. Paixao, (2017).","chicago":"Lukacisinova, Marta, Sebastian Novak, and Tiago Paixao. “Heuristic Prediction for Multiple Stresses.” Public Library of Science, 2017. https://doi.org/10.1371/journal.pcbi.1005609.s003."}},{"citation":{"ista":"Lukacisinova M, Novak S, Paixao T. 2017. Resistance frequencies for different combination strategies, Public Library of Science, 10.1371/journal.pcbi.1005609.s004.","apa":"Lukacisinova, M., Novak, S., & Paixao, T. (2017). Resistance frequencies for different combination strategies. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1005609.s004","ieee":"M. Lukacisinova, S. Novak, and T. Paixao, “Resistance frequencies for different combination strategies.” Public Library of Science, 2017.","ama":"Lukacisinova M, Novak S, Paixao T. Resistance frequencies for different combination strategies. 2017. doi:10.1371/journal.pcbi.1005609.s004","chicago":"Lukacisinova, Marta, Sebastian Novak, and Tiago Paixao. “Resistance Frequencies for Different Combination Strategies.” Public Library of Science, 2017. https://doi.org/10.1371/journal.pcbi.1005609.s004.","mla":"Lukacisinova, Marta, et al. Resistance Frequencies for Different Combination Strategies. Public Library of Science, 2017, doi:10.1371/journal.pcbi.1005609.s004.","short":"M. Lukacisinova, S. Novak, T. Paixao, (2017)."},"doi":"10.1371/journal.pcbi.1005609.s004","date_published":"2017-07-18T00:00:00Z","article_processing_charge":"No","month":"07","day":"18","publisher":"Public Library of Science","department":[{"_id":"ToBo"},{"_id":"CaGu"},{"_id":"NiBa"}],"title":"Resistance frequencies for different combination strategies","status":"public","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","_id":"9852","year":"2017","oa_version":"Published Version","date_created":"2021-08-09T14:11:40Z","date_updated":"2023-02-23T12:55:39Z","related_material":{"record":[{"status":"public","relation":"used_in_publication","id":"696"}]},"author":[{"last_name":"Lukacisinova","first_name":"Marta","orcid":"0000-0002-2519-8004","id":"4342E402-F248-11E8-B48F-1D18A9856A87","full_name":"Lukacisinova, Marta"},{"full_name":"Novak, Sebastian","first_name":"Sebastian","last_name":"Novak","id":"461468AE-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Tiago","last_name":"Paixao","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2361-3953","full_name":"Paixao, Tiago"}],"type":"research_data_reference","abstract":[{"lang":"eng","text":"We show how different combination strategies affect the fraction of individuals that are multi-resistant."}]},{"doi":"10.1371/journal.pgen.1007122.s018","date_published":"2017-12-18T00:00:00Z","citation":{"ama":"Nikolic N, Schreiber F, Dal Co A, et al. Source data for figures and tables. 2017. doi:10.1371/journal.pgen.1007122.s018","ieee":"N. Nikolic et al., “Source data for figures and tables.” Public Library of Science, 2017.","apa":"Nikolic, N., Schreiber, F., Dal Co, A., Kiviet, D., Bergmiller, T., Littmann, S., … Ackermann, M. (2017). Source data for figures and tables. Public Library of Science. https://doi.org/10.1371/journal.pgen.1007122.s018","ista":"Nikolic N, Schreiber F, Dal Co A, Kiviet D, Bergmiller T, Littmann S, Kuypers M, Ackermann M. 2017. Source data for figures and tables, Public Library of Science, 10.1371/journal.pgen.1007122.s018.","short":"N. Nikolic, F. Schreiber, A. Dal Co, D. Kiviet, T. Bergmiller, S. 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.","chicago":"Nikolic, Nela, Frank Schreiber, Alma Dal Co, Daniel Kiviet, Tobias Bergmiller, Sten Littmann, Marcel Kuypers, and Martin Ackermann. “Source Data for Figures and Tables.” Public Library of Science, 2017. https://doi.org/10.1371/journal.pgen.1007122.s018."},"month":"12","day":"18","article_processing_charge":"No","author":[{"full_name":"Nikolic, Nela","last_name":"Nikolic","first_name":"Nela","orcid":"0000-0001-9068-6090","id":"42D9CABC-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Frank","last_name":"Schreiber","full_name":"Schreiber, Frank"},{"full_name":"Dal Co, Alma","first_name":"Alma","last_name":"Dal Co"},{"last_name":"Kiviet","first_name":"Daniel","full_name":"Kiviet, Daniel"},{"first_name":"Tobias","last_name":"Bergmiller","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5396-4346","full_name":"Bergmiller, Tobias"},{"last_name":"Littmann","first_name":"Sten","full_name":"Littmann, Sten"},{"full_name":"Kuypers, Marcel","first_name":"Marcel","last_name":"Kuypers"},{"last_name":"Ackermann","first_name":"Martin","full_name":"Ackermann, Martin"}],"related_material":{"record":[{"id":"541","relation":"used_in_publication","status":"public"}]},"date_updated":"2023-02-23T12:25:04Z","date_created":"2021-08-09T13:27:16Z","oa_version":"Published Version","year":"2017","_id":"9844","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","status":"public","title":"Source data for figures and tables","department":[{"_id":"CaGu"}],"publisher":"Public Library of Science","type":"research_data_reference"},{"oa_version":"Published Version","_id":"561","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":" 13","status":"public","title":"Effects of mutations in phage restriction sites during escape from restriction–modification","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."}],"type":"journal_article","date_published":"2017-12-01T00:00:00Z","citation":{"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.","ista":"Pleska M, Guet CC. 2017. Effects of mutations in phage restriction sites during escape from restriction–modification. Biology Letters. 13(12), 20170646.","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.","short":"M. Pleska, C.C. Guet, Biology Letters 13 (2017).","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."},"publication":"Biology Letters","article_type":"original","article_processing_charge":"No","day":"01","scopus_import":"1","related_material":{"record":[{"id":"9847","relation":"research_data","status":"public"},{"relation":"dissertation_contains","status":"public","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","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C"}],"volume":13,"date_updated":"2023-09-07T11:59:32Z","date_created":"2018-12-11T11:47:11Z","pmid":1,"year":"2017","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.","publisher":"The Royal Society","department":[{"_id":"CaGu"}],"publication_status":"published","publist_id":"7253","article_number":"20170646","doi":"10.1098/rsbl.2017.0646","language":[{"iso":"eng"}],"main_file_link":[{"url":"https://doi.org/10.1098/rsbl.2017.0646","open_access":"1"}],"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)"},{"grant_number":"24210","_id":"251D65D8-B435-11E9-9278-68D0E5697425","name":"Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level (DOC Fellowship)"}],"quality_controlled":"1","publication_identifier":{"issn":["1744-9561"]},"month":"12"},{"alternative_title":["ISTA Thesis"],"type":"dissertation","abstract":[{"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.","lang":"eng"}],"ddc":["576","579"],"title":"Biology of restriction-modification systems at the single-cell and population level","status":"public","_id":"202","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa_version":"Published Version","file":[{"file_name":"IST-2018-916-v1+3_2017_Pleska_Maros_Thesis.pdf","access_level":"open_access","creator":"system","content_type":"application/pdf","file_size":18569590,"file_id":"4710","relation":"main_file","date_updated":"2020-07-14T12:45:24Z","date_created":"2018-12-12T10:08:48Z","checksum":"33cfb59674e91f82e3738396d3fb3776"},{"relation":"source_file","file_id":"6204","checksum":"dcc239968decb233e7f98cf1083d8c26","date_updated":"2020-07-14T12:45:24Z","date_created":"2019-04-05T08:33:14Z","access_level":"closed","file_name":"2017_Pleska_Maros_Thesis.docx","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_size":2801649,"creator":"dernst"}],"pubrep_id":"916","day":"01","article_processing_charge":"No","has_accepted_license":"1","page":"126","citation":{"ista":"Pleska M. 2017. Biology of restriction-modification systems at the single-cell and population level. Institute of Science and Technology Austria.","ieee":"M. Pleska, “Biology of restriction-modification systems at the single-cell and population level,” Institute of Science and Technology Austria, 2017.","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","ama":"Pleska M. Biology of restriction-modification systems at the single-cell and population level. 2017. doi:10.15479/AT:ISTA:th_916","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.","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.","short":"M. Pleska, Biology of Restriction-Modification Systems at the Single-Cell and Population Level, Institute of Science and Technology Austria, 2017."},"date_published":"2017-10-01T00:00:00Z","file_date_updated":"2020-07-14T12:45:24Z","publist_id":"7711","publication_status":"published","publisher":"Institute of Science and Technology Austria","department":[{"_id":"CaGu"}],"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_updated":"2023-09-15T12:04:56Z","date_created":"2018-12-11T11:45:10Z","author":[{"full_name":"Pleska, Maros","last_name":"Pleska","first_name":"Maros","orcid":"0000-0001-7460-7479","id":"4569785E-F248-11E8-B48F-1D18A9856A87"}],"related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"1243"},{"relation":"part_of_dissertation","status":"public","id":"561"},{"relation":"part_of_dissertation","status":"public","id":"457"}]},"month":"10","publication_identifier":{"issn":["2663-337X"]},"project":[{"grant_number":"24210","_id":"251D65D8-B435-11E9-9278-68D0E5697425","name":"Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level (DOC Fellowship)"}],"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"},"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"}],"doi":"10.15479/AT:ISTA:th_916"},{"day":"01","article_processing_charge":"No","has_accepted_license":"1","scopus_import":"1","date_published":"2017-12-01T00:00:00Z","publication":"Acta Informatica","citation":{"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.","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.","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","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.","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","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."},"page":"765 - 787","abstract":[{"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.","lang":"eng"}],"issue":"8","type":"journal_article","pubrep_id":"649","file":[{"creator":"dernst","file_size":755241,"content_type":"application/pdf","file_name":"2017_ActaInformatica_Giacobbe.pdf","access_level":"open_access","date_updated":"2020-07-14T12:44:46Z","date_created":"2019-01-17T15:57:29Z","checksum":"4e661d9135d7f8c342e8e258dee76f3e","file_id":"5841","relation":"main_file"}],"oa_version":"Published Version","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"1351","status":"public","title":"Model checking the evolution of gene regulatory networks","ddc":["006","576"],"intvolume":" 54","month":"12","publication_identifier":{"issn":["00015903"]},"doi":"10.1007/s00236-016-0278-x","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,"external_id":{"isi":["000414343200003"]},"quality_controlled":"1","isi":1,"project":[{"grant_number":"267989","_id":"25EE3708-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"Quantitative Reactive Modeling"},{"grant_number":"S 11407_N23","_id":"25832EC2-B435-11E9-9278-68D0E5697425","name":"Rigorous Systems Engineering","call_identifier":"FWF"},{"_id":"25F42A32-B435-11E9-9278-68D0E5697425","grant_number":"Z211","call_identifier":"FWF","name":"The Wittgenstein Prize"},{"name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","call_identifier":"FP7","grant_number":"618091","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425"},{"name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734"},{"grant_number":"250152","_id":"25B07788-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"Limits to selection in biology and in evolutionary computation"}],"file_date_updated":"2020-07-14T12:44:46Z","publist_id":"5898","ec_funded":1,"author":[{"full_name":"Giacobbe, Mirco","id":"3444EA5E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8180-0904","first_name":"Mirco","last_name":"Giacobbe"},{"last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C"},{"id":"335E5684-F248-11E8-B48F-1D18A9856A87","first_name":"Ashutosh","last_name":"Gupta","full_name":"Gupta, Ashutosh"},{"full_name":"Henzinger, Thomas A","last_name":"Henzinger","first_name":"Thomas A","orcid":"0000−0002−2985−7724","id":"40876CD8-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Paixao","first_name":"Tiago","orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","full_name":"Paixao, Tiago"},{"full_name":"Petrov, Tatjana","orcid":"0000-0002-9041-0905","id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","last_name":"Petrov","first_name":"Tatjana"}],"related_material":{"record":[{"relation":"earlier_version","status":"public","id":"1835"}]},"date_created":"2018-12-11T11:51:32Z","date_updated":"2023-09-20T11:06:03Z","volume":54,"year":"2017","publication_status":"published","publisher":"Springer","department":[{"_id":"ToHe"},{"_id":"CaGu"},{"_id":"NiBa"}]},{"file":[{"creator":"system","content_type":"application/pdf","file_size":710206,"access_level":"open_access","file_name":"IST-2016-658-v1+1_s00453-016-0212-1.pdf","checksum":"7873f665a0c598ac747c908f34cb14b9","date_updated":"2020-07-14T12:44:44Z","date_created":"2018-12-12T10:10:19Z","file_id":"4805","relation":"main_file"}],"oa_version":"Published Version","pubrep_id":"658","intvolume":" 78","status":"public","ddc":["576"],"title":"Towards a runtime comparison of natural and artificial evolution","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"1336","issue":"2","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 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."}],"type":"journal_article","date_published":"2017-06-01T00:00:00Z","page":"681 - 713","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.","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.","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","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"},"publication":"Algorithmica","article_processing_charge":"No","has_accepted_license":"1","day":"01","scopus_import":"1","volume":78,"date_created":"2018-12-11T11:51:27Z","date_updated":"2023-09-20T11:14:42Z","author":[{"orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","last_name":"Paixao","first_name":"Tiago","full_name":"Paixao, Tiago"},{"full_name":"Pérez Heredia, Jorge","last_name":"Pérez Heredia","first_name":"Jorge"},{"first_name":"Dirk","last_name":"Sudholt","full_name":"Sudholt, Dirk"},{"full_name":"Trubenova, Barbora","id":"42302D54-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6873-2967","first_name":"Barbora","last_name":"Trubenova"}],"publisher":"Springer","department":[{"_id":"NiBa"},{"_id":"CaGu"}],"publication_status":"published","year":"2017","publist_id":"5931","ec_funded":1,"file_date_updated":"2020-07-14T12:44:44Z","language":[{"iso":"eng"}],"doi":"10.1007/s00453-016-0212-1","project":[{"_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","grant_number":"618091","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","call_identifier":"FP7"}],"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":["000400379500013"]},"publication_identifier":{"issn":["01784617"]},"month":"06"},{"abstract":[{"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.","lang":"eng"}],"issue":"1","type":"journal_article","oa_version":"None","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"1084","status":"public","title":"Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis","intvolume":" 104","day":"01","article_processing_charge":"No","scopus_import":"1","date_published":"2017-04-01T00:00:00Z","publication":"Molecular Microbiology","citation":{"short":"C. Fang, A.A. Nagy-Staron, M. Grafe, R. Heermann, K. Jung, S. Gebhard, T. Mascher, Molecular Microbiology 104 (2017) 16–31.","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.","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.","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","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.","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."},"page":"16 - 31","publist_id":"6294","author":[{"first_name":"Chong","last_name":"Fang","full_name":"Fang, Chong"},{"full_name":"Nagy-Staron, Anna A","first_name":"Anna A","last_name":"Nagy-Staron","id":"3ABC5BA6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1391-8377"},{"last_name":"Grafe","first_name":"Martin","full_name":"Grafe, Martin"},{"first_name":"Ralf","last_name":"Heermann","full_name":"Heermann, Ralf"},{"first_name":"Kirsten","last_name":"Jung","full_name":"Jung, Kirsten"},{"full_name":"Gebhard, Susanne","last_name":"Gebhard","first_name":"Susanne"},{"first_name":"Thorsten","last_name":"Mascher","full_name":"Mascher, Thorsten"}],"date_created":"2018-12-11T11:50:03Z","date_updated":"2023-09-20T11:48:43Z","volume":104,"year":"2017","publication_status":"published","department":[{"_id":"CaGu"}],"publisher":"Wiley-Blackwell","month":"04","publication_identifier":{"issn":[" 0950382X"]},"doi":"10.1111/mmi.13597","language":[{"iso":"eng"}],"external_id":{"isi":["000398059200002"]},"quality_controlled":"1","isi":1},{"oa_version":"Published Version","file":[{"checksum":"59cdd4400fb41280122d414fea971546","date_created":"2018-12-12T10:17:49Z","date_updated":"2020-07-14T12:48:16Z","relation":"main_file","file_id":"5306","file_size":2441529,"content_type":"application/pdf","creator":"system","access_level":"open_access","file_name":"IST-2017-841-v1+1_elife-25192-v2.pdf"},{"file_size":3752660,"content_type":"application/pdf","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"}],"pubrep_id":"841","ddc":["576"],"title":"On the mechanistic nature of epistasis in a canonical cis-regulatory element","status":"public","intvolume":" 6","_id":"954","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","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","date_published":"2017-05-18T00:00:00Z","publication":"eLife","citation":{"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.","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.","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","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.","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.","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"},"day":"18","has_accepted_license":"1","article_processing_charge":"Yes","scopus_import":"1","date_created":"2018-12-11T11:49:23Z","date_updated":"2023-09-22T10:01:17Z","volume":6,"author":[{"last_name":"Lagator","first_name":"Mato","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","full_name":"Lagator, Mato"},{"orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","last_name":"Paixao","first_name":"Tiago","full_name":"Paixao, Tiago"},{"last_name":"Barton","first_name":"Nicholas H","orcid":"0000-0002-8548-5240","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","full_name":"Barton, Nicholas H"},{"full_name":"Bollback, Jonathan P","last_name":"Bollback","first_name":"Jonathan P","orcid":"0000-0002-4624-4612","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet"}],"publication_status":"published","publisher":"eLife Sciences Publications","department":[{"_id":"CaGu"},{"_id":"NiBa"},{"_id":"JoBo"}],"year":"2017","file_date_updated":"2020-07-14T12:48:16Z","ec_funded":1,"publist_id":"6460","article_number":"e25192","language":[{"iso":"eng"}],"doi":"10.7554/eLife.25192","isi":1,"quality_controlled":"1","project":[{"_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","grant_number":"618091","call_identifier":"FP7","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation"},{"grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme"},{"call_identifier":"H2020","name":"Selective Barriers to Horizontal Gene Transfer","_id":"2578D616-B435-11E9-9278-68D0E5697425","grant_number":"648440"}],"external_id":{"isi":["000404024800001"]},"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":"05","publication_identifier":{"issn":["2050084X"]}},{"publist_id":"6391","ec_funded":1,"file_date_updated":"2018-12-12T10:11:29Z","author":[{"last_name":"Lang","first_name":"Moritz","id":"29E0800A-F248-11E8-B48F-1D18A9856A87","full_name":"Lang, Moritz"},{"first_name":"Eduardo","last_name":"Sontag","full_name":"Sontag, Eduardo"}],"volume":"81C","date_created":"2018-12-11T11:49:39Z","date_updated":"2023-10-17T08:51:18Z","year":"2017","publisher":"International Federation of Automatic Control","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publication_status":"published","publication_identifier":{"issn":["0005-1098"]},"month":"06","doi":"10.1016/j.automatica.2017.03.030","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":["000403513900006"]},"project":[{"call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme","grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425"}],"quality_controlled":"1","isi":1,"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","pubrep_id":"813","oa_version":"Published Version","file":[{"content_type":"application/pdf","file_size":1401954,"creator":"system","access_level":"open_access","file_name":"IST-2017-813-v1+1_ZerosOfNonlinearSystems.pdf","date_updated":"2018-12-12T10:11:29Z","date_created":"2018-12-12T10:11:29Z","relation":"main_file","file_id":"4884"}],"_id":"1007","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","ddc":["000"],"title":"Zeros of nonlinear systems with input invariances","has_accepted_license":"1","article_processing_charge":"Yes (in subscription journal)","day":"01","scopus_import":"1","date_published":"2017-06-01T00:00:00Z","citation":{"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.","short":"M. Lang, E. Sontag, Automatica 81C (2017) 46–55.","chicago":"Lang, Moritz, and Eduardo Sontag. “Zeros of Nonlinear Systems with Input Invariances.” Automatica. International Federation of Automatic Control, 2017. https://doi.org/10.1016/j.automatica.2017.03.030.","ama":"Lang M, Sontag E. Zeros of nonlinear systems with input invariances. Automatica. 2017;81C:46-55. doi:10.1016/j.automatica.2017.03.030","ista":"Lang M, Sontag E. 2017. Zeros of nonlinear systems with input invariances. Automatica. 81C, 46–55.","apa":"Lang, M., & Sontag, E. (2017). Zeros of nonlinear systems with input invariances. Automatica. International Federation of Automatic Control. https://doi.org/10.1016/j.automatica.2017.03.030","ieee":"M. Lang and E. Sontag, “Zeros of nonlinear systems with input invariances,” Automatica, vol. 81C. International Federation of Automatic Control, pp. 46–55, 2017."},"publication":"Automatica","page":"46 - 55"},{"department":[{"_id":"CaGu"}],"publisher":"Institute of Science and Technology Austria","title":"Fastq files for \"Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection\"","ddc":["576"],"status":"public","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"5564","year":"2017","file":[{"creator":"system","content_type":"application/zip","file_size":1225959109,"file_name":"IST-2017-65-v1+1_D_anc_1.fastq.zip","access_level":"open_access","date_created":"2018-12-12T13:03:18Z","date_updated":"2020-07-14T12:47:03Z","checksum":"31a0c01d022721073241a23d192cc37e","file_id":"5627","relation":"main_file"},{"date_created":"2018-12-12T13:03:30Z","date_updated":"2020-07-14T12:47:03Z","checksum":"d8f26f83ce7e7e45436121f9c6cd9b83","relation":"main_file","file_id":"5628","file_size":1422656107,"content_type":"application/zip","creator":"system","file_name":"IST-2017-65-v1+1_D_anc_2.fastq.zip","access_level":"open_access"},{"access_level":"open_access","file_name":"IST-2017-65-v1+2_D_A11_1.fastq.zip","creator":"system","content_type":"application/zip","file_size":565014975,"file_id":"5629","relation":"main_file","checksum":"e07b99bcfe55b5f132ca03b8b48c8cbc","date_updated":"2020-07-14T12:47:03Z","date_created":"2018-12-12T13:03:33Z"},{"relation":"main_file","file_id":"5630","checksum":"eda86143d5f32d844b54f8530041e32b","date_created":"2018-12-12T13:03:42Z","date_updated":"2020-07-14T12:47:03Z","access_level":"open_access","file_name":"IST-2017-65-v1+3_D_A11_2.fastq.zip","content_type":"application/zip","file_size":564490030,"creator":"system"},{"file_id":"5631","relation":"main_file","checksum":"906d44f950c1626d9b99f34fbf89cb12","date_created":"2018-12-12T13:03:46Z","date_updated":"2020-07-14T12:47:03Z","access_level":"open_access","file_name":"IST-2017-65-v1+4_D_C10_1.fastq.zip","creator":"system","file_size":875430169,"content_type":"application/zip"},{"file_id":"5632","relation":"main_file","checksum":"6ca14a032a79e0c787106bdf635725c9","date_updated":"2020-07-14T12:47:03Z","date_created":"2018-12-12T13:03:54Z","access_level":"open_access","file_name":"IST-2017-65-v1+6_D_C08_2.fastq.zip","creator":"system","content_type":"application/zip","file_size":638298201},{"checksum":"66ab16ddb5ba64b2e263ef746ebf2893","date_updated":"2020-07-14T12:47:03Z","date_created":"2018-12-12T13:04:01Z","relation":"main_file","file_id":"5633","file_size":894702866,"content_type":"application/zip","creator":"system","access_level":"open_access","file_name":"IST-2017-65-v1+5_D_C10_2.fastq.zip"},{"content_type":"application/zip","file_size":623648989,"creator":"system","access_level":"open_access","file_name":"IST-2017-65-v1+7_D_C08_1.fastq.zip","checksum":"82607970174f8d37773b7d3acc712195","date_updated":"2020-07-14T12:47:03Z","date_created":"2018-12-12T13:04:07Z","relation":"main_file","file_id":"5634"},{"file_size":259359583,"content_type":"application/zip","creator":"system","access_level":"open_access","file_name":"IST-2017-65-v1+8_D_D08_1.fastq.zip","checksum":"225c30b243268c7dda9d6f8327933252","date_updated":"2020-07-14T12:47:03Z","date_created":"2018-12-12T13:04:11Z","relation":"main_file","file_id":"5635"}],"oa_version":"Published Version","date_updated":"2024-02-21T13:47:28Z","date_created":"2018-12-12T12:31:33Z","related_material":{"record":[{"relation":"research_paper","status":"public","id":"704"}]},"author":[{"full_name":"Steinrück, Magdalena","orcid":"0000-0003-1229-9719","id":"2C023F40-F248-11E8-B48F-1D18A9856A87","last_name":"Steinrück","first_name":"Magdalena"},{"full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C"}],"type":"research_data","datarep_id":"65","file_date_updated":"2020-07-14T12:47:03Z","abstract":[{"text":"Compressed Fastq files with whole-genome sequencing data of IS-wt strain D and clones from four evolved populations (A11, C08, C10, D08). Information on this data collection is available in the Methods Section of the primary publication.","lang":"eng"}],"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":"Steinrück M, Guet CC. Fastq files for “Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection.” 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.","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.","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."},"oa":1,"date_published":"2017-04-11T00:00:00Z","doi":"10.15479/AT:ISTA:65","has_accepted_license":"1","article_processing_charge":"No","month":"04","day":"11"},{"abstract":[{"lang":"eng","text":"This repository contains the data collected for the manuscript \"Biased partitioning of the multi-drug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity\".\r\nThe data is compressed into a single archive. 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":[{"id":"665","relation":"research_paper","status":"public"}]},"author":[{"full_name":"Bergmiller, Tobias","orcid":"0000-0001-5396-4346","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","last_name":"Bergmiller","first_name":"Tobias"},{"orcid":"0000-0003-2912-6769","id":"2B8A40DA-F248-11E8-B48F-1D18A9856A87","last_name":"Andersson","first_name":"Anna M","full_name":"Andersson, Anna M"},{"full_name":"Tomasek, Kathrin","orcid":"0000-0003-3768-877X","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","last_name":"Tomasek","first_name":"Kathrin"},{"full_name":"Balleza, Enrique","first_name":"Enrique","last_name":"Balleza"},{"full_name":"Kiviet, Daniel","first_name":"Daniel","last_name":"Kiviet"},{"orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","last_name":"Hauschild","first_name":"Robert","full_name":"Hauschild, Robert"},{"full_name":"Tkacik, Gasper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","first_name":"Gasper","last_name":"Tkacik"},{"full_name":"Guet, Calin C","last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"}],"oa_version":"Published Version","file":[{"relation":"main_file","file_id":"5603","checksum":"d77859af757ac8025c50c7b12b52eaf3","date_updated":"2020-07-14T12:47:03Z","date_created":"2018-12-12T13:02:38Z","access_level":"open_access","file_name":"IST-2017-53-v1+1_Data_MDE.zip","content_type":"application/zip","file_size":6773204,"creator":"system"}],"date_updated":"2024-02-21T13:49:00Z","date_created":"2018-12-12T12:31:32Z","year":"2017","_id":"5560","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"Bio"}],"publisher":"Institute of Science and Technology Austria","status":"public","ddc":["571"],"title":"Biased partitioning of the multi-drug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity","article_processing_charge":"No","has_accepted_license":"1","month":"03","day":"10","keyword":["single cell microscopy","mother machine microfluidic device","AcrAB-TolC pump","multi-drug efflux","Escherichia coli"],"date_published":"2017-03-10T00:00:00Z","doi":"10.15479/AT:ISTA:53","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":{"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","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.","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.","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","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.","short":"T. Bergmiller, A.M. Andersson, K. Tomasek, E. Balleza, D. Kiviet, R. Hauschild, G. Tkačik, C.C. Guet, (2017).","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."}},{"project":[{"_id":"254E9036-B435-11E9-9278-68D0E5697425","grant_number":"P28844-B27","name":"Biophysics of information processing in gene regulation","call_identifier":"FWF"}],"quality_controlled":"1","language":[{"iso":"eng"}],"doi":"10.1126/science.aaf4762","publication_identifier":{"issn":["00368075"]},"month":"04","department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"Bio"}],"publisher":"American Association for the Advancement of Science","publication_status":"published","year":"2017","volume":356,"date_updated":"2024-02-21T13:49:00Z","date_created":"2018-12-11T11:47:48Z","related_material":{"record":[{"id":"5560","status":"public","relation":"popular_science"}]},"author":[{"full_name":"Bergmiller, Tobias","first_name":"Tobias","last_name":"Bergmiller","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5396-4346"},{"full_name":"Andersson, Anna M","first_name":"Anna M","last_name":"Andersson","id":"2B8A40DA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2912-6769"},{"first_name":"Kathrin","last_name":"Tomasek","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3768-877X","full_name":"Tomasek, Kathrin"},{"last_name":"Balleza","first_name":"Enrique","full_name":"Balleza, Enrique"},{"last_name":"Kiviet","first_name":"Daniel","full_name":"Kiviet, Daniel"},{"full_name":"Hauschild, Robert","first_name":"Robert","last_name":"Hauschild","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9843-3522"},{"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","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet"}],"publist_id":"7064","page":"311 - 315","article_type":"original","citation":{"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.","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.","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","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."},"publication":"Science","date_published":"2017-04-21T00:00:00Z","scopus_import":1,"article_processing_charge":"No","day":"21","intvolume":" 356","status":"public","title":"Biased partitioning of the multidrug efflux pump AcrAB TolC underlies long lived phenotypic heterogeneity","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"665","oa_version":"None","type":"journal_article","issue":"6335","abstract":[{"lang":"eng","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."}]},{"issue":"16","abstract":[{"lang":"eng","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."}],"type":"journal_article","oa_version":"Published Version","file":[{"file_name":"2017_communications_Kainrath.pdf","access_level":"open_access","file_size":2614942,"content_type":"application/pdf","creator":"dernst","relation":"main_file","file_id":"5845","date_created":"2019-01-18T09:39:55Z","date_updated":"2019-01-18T09:39:55Z","success":1}],"_id":"1028","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","intvolume":" 56","ddc":["540"],"status":"public","title":"Green-light-induced inactivation of receptor signaling using cobalamin-binding domains","has_accepted_license":"1","article_processing_charge":"No","day":"20","scopus_import":"1","date_published":"2017-03-20T00:00:00Z","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","ec_funded":1,"publist_id":"6362","file_date_updated":"2019-01-18T09:39:55Z","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"418"},{"relation":"part_of_dissertation","status":"public","id":"7680"}]},"author":[{"id":"32CFBA64-F248-11E8-B48F-1D18A9856A87","first_name":"Stephanie","last_name":"Kainrath","full_name":"Kainrath, Stephanie"},{"full_name":"Stadler, Manuela","last_name":"Stadler","first_name":"Manuela"},{"last_name":"Gschaider-Reichhart","first_name":"Eva","orcid":"0000-0002-7218-7738","id":"3FEE232A-F248-11E8-B48F-1D18A9856A87","full_name":"Gschaider-Reichhart, Eva"},{"full_name":"Distel, Martin","last_name":"Distel","first_name":"Martin"},{"first_name":"Harald L","last_name":"Janovjak","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8023-9315","full_name":"Janovjak, Harald L"}],"volume":56,"date_created":"2018-12-11T11:49:46Z","date_updated":"2024-03-28T23:30:13Z","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","publisher":"Wiley-Blackwell","department":[{"_id":"CaGu"},{"_id":"HaJa"}],"publication_status":"published","publication_identifier":{"issn":["14337851"]},"month":"03","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"},"external_id":{"isi":["000398154000038"]},"oa":1,"project":[{"grant_number":"303564","_id":"25548C20-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"Microbial Ion Channels for Synthetic Neurobiology"},{"grant_number":"W1232-B24","_id":"26AA4EF2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Molecular Drug Targets [do not use to be deleted]"}],"quality_controlled":"1","isi":1},{"related_material":{"record":[{"relation":"popular_science","status":"public","id":"5564"},{"status":"public","relation":"dissertation_contains","id":"26"}]},"author":[{"id":"2C023F40-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1229-9719","first_name":"Magdalena","last_name":"Steinrück","full_name":"Steinrück, 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","year":"2017","department":[{"_id":"CaGu"}],"publisher":"eLife Sciences Publications","publication_status":"published","publist_id":"6990","file_date_updated":"2020-07-14T12:47:48Z","article_number":"e25100","doi":"10.7554/eLife.25100","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"},"quality_controlled":"1","publication_identifier":{"issn":["2050084X"]},"month":"07","pubrep_id":"890","file":[{"date_created":"2018-12-12T10:12:54Z","date_updated":"2020-07-14T12:47:48Z","checksum":"6b908b5db9f61f6820ebd7f8fa815571","relation":"main_file","file_id":"4975","content_type":"application/pdf","file_size":2092088,"creator":"system","file_name":"IST-2017-890-v1+1_elife-25100-v1.pdf","access_level":"open_access"},{"file_id":"4976","relation":"main_file","date_updated":"2020-07-14T12:47:48Z","date_created":"2018-12-12T10:12:55Z","checksum":"ca21530389b720243552678125fdba35","file_name":"IST-2017-890-v1+2_elife-25100-figures-v1.pdf","access_level":"open_access","creator":"system","file_size":3428681,"content_type":"application/pdf"}],"oa_version":"Published Version","_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","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"}],"type":"journal_article","date_published":"2017-07-25T00:00:00Z","citation":{"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","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","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.","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)."},"publication":"eLife","has_accepted_license":"1","day":"25","scopus_import":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"},"quality_controlled":"1","project":[{"grant_number":"618091","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","call_identifier":"FP7"}],"doi":"10.1371/journal.pcbi.1005609","language":[{"iso":"eng"}],"month":"07","publication_identifier":{"issn":["1553734X"]},"year":"2017","publication_status":"published","department":[{"_id":"ToBo"},{"_id":"NiBa"},{"_id":"CaGu"}],"publisher":"Public Library of Science","author":[{"first_name":"Marta","last_name":"Lukacisinova","id":"4342E402-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2519-8004","full_name":"Lukacisinova, Marta"},{"id":"461468AE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2519-824X","first_name":"Sebastian","last_name":"Novak","full_name":"Novak, Sebastian"},{"full_name":"Paixao, Tiago","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2361-3953","first_name":"Tiago","last_name":"Paixao"}],"related_material":{"record":[{"status":"public","relation":"research_data","id":"9849"},{"id":"9850","status":"public","relation":"research_data"},{"relation":"research_data","status":"public","id":"9851"},{"status":"public","relation":"research_data","id":"9852"},{"id":"6263","relation":"dissertation_contains","status":"public"}]},"date_created":"2018-12-11T11:47:58Z","date_updated":"2024-03-28T23:30:28Z","volume":13,"article_number":"e1005609","file_date_updated":"2020-07-14T12:47:46Z","ec_funded":1,"publist_id":"7004","publication":"PLoS Computational Biology","citation":{"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.","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.","short":"M. Lukacisinova, S. Novak, T. Paixao, PLoS Computational Biology 13 (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.","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.","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","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"},"article_type":"original","date_published":"2017-07-18T00:00:00Z","scopus_import":1,"day":"18","has_accepted_license":"1","_id":"696","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Stress induced mutagenesis: Stress diversity facilitates the persistence of mutator genes","ddc":["576"],"status":"public","intvolume":" 13","pubrep_id":"894","oa_version":"Published Version","file":[{"file_id":"5117","relation":"main_file","date_created":"2018-12-12T10:15:01Z","date_updated":"2020-07-14T12:47:46Z","checksum":"9143c290fa6458ed2563bff4b295554a","file_name":"IST-2017-894-v1+1_journal.pcbi.1005609.pdf","access_level":"open_access","creator":"system","file_size":3775716,"content_type":"application/pdf"}],"type":"journal_article","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."}],"issue":"7"},{"date_published":"2017-10-23T00:00:00Z","publication":"Developmental Cell","citation":{"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.","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.","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.","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","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.","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."},"page":"198 - 211","day":"23","article_processing_charge":"No","scopus_import":"1","oa_version":"None","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"735","title":"An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate","status":"public","intvolume":" 43","abstract":[{"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.","lang":"eng"}],"issue":"2","type":"journal_article","doi":"10.1016/j.devcel.2017.09.014","language":[{"iso":"eng"}],"external_id":{"isi":["000413443700011"]},"quality_controlled":"1","isi":1,"project":[{"name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425"},{"_id":"252DD2A6-B435-11E9-9278-68D0E5697425","grant_number":"I2058","name":"Cell segregation in gastrulation: the role of cell fate specification","call_identifier":"FWF"}],"month":"10","publication_identifier":{"issn":["15345807"]},"author":[{"full_name":"Barone, Vanessa","orcid":"0000-0003-2676-3367","id":"419EECCC-F248-11E8-B48F-1D18A9856A87","last_name":"Barone","first_name":"Vanessa"},{"full_name":"Lang, Moritz","last_name":"Lang","first_name":"Moritz","id":"29E0800A-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Gabriel","last_name":"Krens","id":"2B819732-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4761-5996","full_name":"Krens, Gabriel"},{"last_name":"Pradhan","first_name":"Saurabh","full_name":"Pradhan, Saurabh"},{"id":"40B34FE2-F248-11E8-B48F-1D18A9856A87","last_name":"Shamipour","first_name":"Shayan","full_name":"Shamipour, Shayan"},{"full_name":"Sako, Keisuke","last_name":"Sako","first_name":"Keisuke","orcid":"0000-0002-6453-8075","id":"3BED66BE-F248-11E8-B48F-1D18A9856A87"},{"id":"2F74BCDE-F248-11E8-B48F-1D18A9856A87","first_name":"Mateusz K","last_name":"Sikora","full_name":"Sikora, Mateusz K"},{"full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C"},{"orcid":"0000-0002-0912-4566","id":"39427864-F248-11E8-B48F-1D18A9856A87","last_name":"Heisenberg","first_name":"Carl-Philipp J","full_name":"Heisenberg, Carl-Philipp J"}],"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"961"},{"id":"8350","status":"public","relation":"dissertation_contains"}]},"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","ec_funded":1,"publist_id":"6934"},{"abstract":[{"lang":"eng","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."}],"issue":"10","publist_id":"6390","type":"journal_article","date_created":"2018-12-11T11:49:40Z","date_updated":"2021-01-12T06:47:37Z","oa_version":"None","volume":5,"author":[{"full_name":"Gnügge, Robert","first_name":"Robert","last_name":"Gnügge"},{"first_name":"Lekshmi","last_name":"Dharmarajan","full_name":"Dharmarajan, Lekshmi"},{"first_name":"Moritz","last_name":"Lang","id":"29E0800A-F248-11E8-B48F-1D18A9856A87","full_name":"Lang, Moritz"},{"full_name":"Stelling, Jörg","first_name":"Jörg","last_name":"Stelling"}],"status":"public","publication_status":"published","title":"An orthogonal permease–inducer–repressor feedback loop shows bistability","publisher":"American Chemical Society","department":[{"_id":"CaGu"}],"intvolume":" 5","_id":"1008","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","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.","year":"2016","day":"05","month":"05","language":[{"iso":"eng"}],"date_published":"2016-05-05T00:00:00Z","doi":"10.1021/acssynbio.6b00013","quality_controlled":"1","page":"1098 - 1107","publication":"ACS Synthetic Biology","citation":{"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.","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.","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","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","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.","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.","short":"R. Gnügge, L. Dharmarajan, M. Lang, J. Stelling, ACS Synthetic Biology 5 (2016) 1098–1107."}},{"quality_controlled":"1","language":[{"iso":"eng"}],"doi":"10.1137/15M103306X","month":"11","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publisher":"Society for Industrial and Applied Mathematics ","publication_status":"published","year":"2016","volume":38,"date_updated":"2021-01-12T06:48:49Z","date_created":"2018-12-11T11:50:31Z","author":[{"full_name":"Lang, Moritz","first_name":"Moritz","last_name":"Lang","id":"29E0800A-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Stelling, Jörg","last_name":"Stelling","first_name":"Jörg"}],"publist_id":"6186","file_date_updated":"2020-07-14T12:44:37Z","page":"B988 - B1008","citation":{"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.","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.","short":"M. Lang, J. Stelling, SIAM Journal on Scientific Computing 38 (2016) B988–B1008.","ista":"Lang M, Stelling J. 2016. Modular parameter identification of biomolecular networks. SIAM Journal on Scientific Computing. 38(6), B988–B1008.","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","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.","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"},"publication":"SIAM Journal on Scientific Computing","date_published":"2016-11-15T00:00:00Z","scopus_import":1,"has_accepted_license":"1","day":"15","intvolume":" 38","ddc":["003","518","570","621"],"title":"Modular parameter identification of biomolecular networks","status":"public","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","_id":"1170","file":[{"file_id":"5095","relation":"main_file","date_created":"2018-12-12T10:14:41Z","date_updated":"2020-07-14T12:44:37Z","checksum":"781bc3ffd30b2dd65b7727c5a285fc78","file_name":"IST-2017-811-v1+1_modular_parameter_identification.pdf","access_level":"local","creator":"system","content_type":"application/pdf","file_size":871964}],"oa_version":"Submitted Version","pubrep_id":"811","type":"journal_article","issue":"6","abstract":[{"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.","lang":"eng"}]},{"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."}],"publist_id":"6114","type":"conference","author":[{"full_name":"Mikić, Gregor","first_name":"Gregor","last_name":"Mikić"},{"first_name":"Alex","last_name":"Stoll","full_name":"Stoll, Alex"},{"full_name":"Bevirt, Joe","last_name":"Bevirt","first_name":"Joe"},{"full_name":"Grah, Rok","id":"483E70DE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2539-3560","first_name":"Rok","last_name":"Grah"},{"last_name":"Moore","first_name":"Mark","full_name":"Moore, Mark"}],"date_updated":"2023-02-21T10:17:50Z","date_created":"2018-12-11T11:50:47Z","oa_version":"Preprint","year":"2016","_id":"1220","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","status":"public","title":"Fuselage boundary layer ingestion propulsion applied to a thin haul commuter aircraft for optimal efficiency","publication_status":"published","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publisher":"AIAA","month":"06","day":"01","scopus_import":1,"conference":{"name":"AIAA: Aviation Technology, Integration, and Operations Conference","end_date":"2016-06-17","location":"Washington, D.C., USA","start_date":"2016-06-13"},"date_published":"2016-06-01T00:00:00Z","doi":"10.2514/6.2016-3764","language":[{"iso":"eng"}],"citation":{"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.","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.","short":"G. Mikić, A. Stoll, J. Bevirt, R. Grah, M. Moore, in:, AIAA, 2016, pp. 1–19.","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.","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","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"},"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"}],"oa":1,"quality_controlled":"1","page":"1 - 19"},{"main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5069154/"}],"oa":1,"quality_controlled":"1","doi":"10.1038/nchembio.2176","language":[{"iso":"eng"}],"month":"11","year":"2016","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","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publisher":"Nature Publishing Group","publication_status":"published","author":[{"first_name":"Laura","last_name":"Stone","full_name":"Stone, Laura"},{"last_name":"Baym","first_name":"Michael","full_name":"Baym, Michael"},{"last_name":"Lieberman","first_name":"Tami","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"},{"first_name":"Jon","last_name":"Clardy","full_name":"Clardy, Jon"},{"last_name":"Kishony","first_name":"Roy","full_name":"Kishony, Roy"}],"volume":12,"date_created":"2018-12-11T11:51:10Z","date_updated":"2021-01-12T06:49:39Z","publist_id":"6026","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","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.","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","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.","short":"L. Stone, M. Baym, T. Lieberman, R.P. Chait, J. Clardy, R. Kishony, Nature Chemical Biology 12 (2016) 902–904.","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.","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","page":"902 - 904","date_published":"2016-11-01T00:00:00Z","scopus_import":1,"day":"01","_id":"1290","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","intvolume":" 12","title":"Compounds that select against the tetracycline-resistance efflux pump","status":"public","oa_version":"Preprint","type":"journal_article","issue":"11","abstract":[{"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.","lang":"eng"}]},{"month":"07","quality_controlled":"1","project":[{"_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734","call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme"}],"conference":{"name":"ACC: American Control Conference","end_date":"2016-07-08","start_date":"2016-07-06","location":"Boston, MA, USA"},"doi":"10.1109/ACC.2016.7526722","language":[{"iso":"eng"}],"article_number":"7526722","file_date_updated":"2020-07-14T12:44:43Z","ec_funded":1,"publist_id":"5950","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.","year":"2016","publication_status":"published","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publisher":"IEEE","author":[{"last_name":"Lang","first_name":"Moritz","id":"29E0800A-F248-11E8-B48F-1D18A9856A87","full_name":"Lang, Moritz"},{"full_name":"Sontag, Eduardo","first_name":"Eduardo","last_name":"Sontag"}],"date_updated":"2021-01-12T06:49:51Z","date_created":"2018-12-11T11:51:21Z","volume":"2016-July","scopus_import":1,"day":"28","has_accepted_license":"1","citation":{"ama":"Lang M, Sontag E. Scale-invariant systems realize nonlinear differential operators. In: Vol 2016-July. IEEE; 2016. doi:10.1109/ACC.2016.7526722","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.","ista":"Lang M, Sontag E. 2016. Scale-invariant systems realize nonlinear differential operators. ACC: American Control Conference vol. 2016–July, 7526722.","short":"M. Lang, E. Sontag, in:, IEEE, 2016.","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.","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."},"date_published":"2016-07-28T00:00:00Z","type":"conference","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"}],"_id":"1320","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","title":"Scale-invariant systems realize nonlinear differential operators","status":"public","ddc":["003","621"],"pubrep_id":"810","file":[{"access_level":"local","file_name":"IST-2017-810-v1+1_root.pdf","creator":"system","content_type":"application/pdf","file_size":539166,"file_id":"5203","relation":"main_file","checksum":"7219432b43defc62a0d45f48d4ce6a19","date_created":"2018-12-12T10:16:17Z","date_updated":"2020-07-14T12:44:43Z"}],"oa_version":"Preprint"},{"month":"01","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":"10.1038/ncomms10333","article_number":"10333","publist_id":"5936","file_date_updated":"2020-07-14T12:44:44Z","publisher":"Nature Publishing Group","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publication_status":"published","year":"2016","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.","volume":7,"date_updated":"2021-01-12T06:49:57Z","date_created":"2018-12-11T11:51:25Z","author":[{"id":"3464AE84-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0876-3187","first_name":"Remy P","last_name":"Chait","full_name":"Chait, Remy P"},{"full_name":"Palmer, Adam","last_name":"Palmer","first_name":"Adam"},{"last_name":"Yelin","first_name":"Idan","full_name":"Yelin, Idan"},{"last_name":"Kishony","first_name":"Roy","full_name":"Kishony, Roy"}],"scopus_import":1,"has_accepted_license":"1","day":"20","citation":{"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.","short":"R.P. Chait, A. Palmer, I. Yelin, R. Kishony, Nature Communications 7 (2016).","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.","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","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.","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."},"publication":"Nature Communications","date_published":"2016-01-20T00:00:00Z","type":"journal_article","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."}],"intvolume":" 7","ddc":["570","579"],"status":"public","title":"Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments","_id":"1332","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","file":[{"file_id":"5039","relation":"main_file","date_created":"2018-12-12T10:13:52Z","date_updated":"2020-07-14T12:44:44Z","checksum":"ef147bcbb8bd37e9079cf3ce06f5815d","file_name":"IST-2016-662-v1+1_ncomms10333.pdf","access_level":"open_access","creator":"system","file_size":1844107,"content_type":"application/pdf"}],"oa_version":"Published Version","pubrep_id":"662"},{"scopus_import":1,"day":"09","month":"09","publication":"Science","oa":1,"main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5534434/","open_access":"1"}],"citation":{"short":"M. Baym, T. Lieberman, E. Kelsic, R.P. Chait, R. Gross, I. Yelin, R. Kishony, Science 353 (2016) 1147–1151.","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.","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.","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","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","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.","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."},"quality_controlled":"1","page":"1147 - 1151","date_published":"2016-09-09T00:00:00Z","doi":"10.1126/science.aag0822","language":[{"iso":"eng"}],"type":"journal_article","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"}],"publist_id":"5911","issue":"6304","_id":"1342","year":"2016","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","title":"Spatiotemporal microbial evolution on antibiotic landscapes","status":"public","publication_status":"published","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publisher":"American Association for the Advancement of Science","intvolume":" 353","author":[{"full_name":"Baym, Michael","last_name":"Baym","first_name":"Michael"},{"last_name":"Lieberman","first_name":"Tami","full_name":"Lieberman, Tami"},{"full_name":"Kelsic, Eric","last_name":"Kelsic","first_name":"Eric"},{"orcid":"0000-0003-0876-3187","id":"3464AE84-F248-11E8-B48F-1D18A9856A87","last_name":"Chait","first_name":"Remy P","full_name":"Chait, Remy P"},{"full_name":"Gross, Rotem","last_name":"Gross","first_name":"Rotem"},{"last_name":"Yelin","first_name":"Idan","full_name":"Yelin, Idan"},{"first_name":"Roy","last_name":"Kishony","full_name":"Kishony, Roy"}],"date_created":"2018-12-11T11:51:29Z","date_updated":"2021-01-12T06:50:01Z","volume":353,"oa_version":"Preprint"},{"month":"07","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":"Speed of Adaptation in Population Genetics and Evolutionary Computation","call_identifier":"FP7","grant_number":"618091","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425"}],"quality_controlled":"1","doi":"10.1145/2908812.2908909","conference":{"name":"GECCO: Genetic and evolutionary computation conference","end_date":"2016-07-24","location":"Denver, CO, USA","start_date":"2016-07-20"},"language":[{"iso":"eng"}],"publist_id":"5900","ec_funded":1,"file_date_updated":"2020-07-14T12:44:45Z","year":"2016","department":[{"_id":"NiBa"},{"_id":"CaGu"}],"publisher":"ACM","publication_status":"published","author":[{"first_name":"Pietro","last_name":"Oliveto","full_name":"Oliveto, Pietro"},{"full_name":"Paixao, Tiago","orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","last_name":"Paixao","first_name":"Tiago"},{"full_name":"Heredia, Jorge","first_name":"Jorge","last_name":"Heredia"},{"first_name":"Dirk","last_name":"Sudholt","full_name":"Sudholt, Dirk"},{"id":"42302D54-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6873-2967","first_name":"Barbora","last_name":"Trubenova","full_name":"Trubenova, Barbora"}],"date_created":"2018-12-11T11:51:31Z","date_updated":"2021-01-12T06:50:03Z","scopus_import":1,"has_accepted_license":"1","day":"20","citation":{"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.","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","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.","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","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.","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.","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."},"publication":"Proceedings of the Genetic and Evolutionary Computation Conference 2016 ","page":"1163 - 1170","date_published":"2016-07-20T00:00:00Z","type":"conference","abstract":[{"lang":"eng","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."}],"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","_id":"1349","ddc":["576"],"status":"public","title":"When non-elitism outperforms elitism for crossing fitness valleys","pubrep_id":"650","file":[{"date_created":"2018-12-12T10:16:27Z","date_updated":"2020-07-14T12:44:45Z","checksum":"a1896e39e4113f2711e46b435d5f3e69","relation":"main_file","file_id":"5214","file_size":979026,"content_type":"application/pdf","creator":"system","file_name":"IST-2016-650-v1+1_p1163-oliveto.pdf","access_level":"open_access"}],"oa_version":"Published Version"},{"publist_id":"5886","ec_funded":1,"department":[{"_id":"NiBa"},{"_id":"CaGu"}],"publisher":"National Academy of Sciences","publication_status":"published","pmid":1,"year":"2016","volume":113,"date_updated":"2021-01-12T06:50:08Z","date_created":"2018-12-11T11:51:34Z","author":[{"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","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8548-5240","first_name":"Nicholas H","last_name":"Barton"}],"month":"04","project":[{"_id":"25B07788-B435-11E9-9278-68D0E5697425","grant_number":"250152","call_identifier":"FP7","name":"Limits to selection in biology and in evolutionary computation"},{"name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","call_identifier":"FP7","grant_number":"618091","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425"}],"quality_controlled":"1","external_id":{"pmid":["27044080"]},"oa":1,"main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4843425/","open_access":"1"}],"language":[{"iso":"eng"}],"doi":"10.1073/pnas.1518830113","type":"journal_article","issue":"16","abstract":[{"lang":"eng","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."}],"intvolume":" 113","title":"The effect of gene interactions on the long-term response to selection","status":"public","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"1359","oa_version":"Published Version","scopus_import":1,"article_processing_charge":"No","day":"19","page":"4422 - 4427","article_type":"original","citation":{"ista":"Paixao T, Barton NH. 2016. The effect of gene interactions on the long-term response to selection. PNAS. 113(16), 4422–4427.","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.","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","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","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.","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."},"publication":"PNAS","date_published":"2016-04-19T00:00:00Z"},{"type":"journal_article","abstract":[{"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.","lang":"eng"}],"issue":"3","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","_id":"1427","status":"public","ddc":["570","576"],"title":"Epistatic interactions in the arabinose cis-regulatory element","intvolume":" 33","pubrep_id":"588","oa_version":"Published Version","file":[{"file_name":"IST-2016-588-v1+1_Mol_Biol_Evol-2016-Lagator-761-9.pdf","access_level":"open_access","file_size":648115,"content_type":"application/pdf","creator":"system","relation":"main_file","file_id":"4751","date_updated":"2020-07-14T12:44:53Z","date_created":"2018-12-12T10:09:27Z","checksum":"1f456ce1d2aa2f67176a1709f9702ecf"}],"scopus_import":1,"day":"01","has_accepted_license":"1","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.","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.","short":"M. Lagator, C. Igler, A. Moreno, C.C. Guet, J.P. Bollback, Molecular Biology and Evolution 33 (2016) 761–769.","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.","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","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","date_published":"2016-03-01T00:00:00Z","file_date_updated":"2020-07-14T12:44:53Z","ec_funded":1,"publist_id":"5772","year":"2016","publication_status":"published","publisher":"Oxford University Press","department":[{"_id":"CaGu"},{"_id":"JoBo"}],"author":[{"full_name":"Lagator, Mato","last_name":"Lagator","first_name":"Mato","id":"345D25EC-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Igler","first_name":"Claudia","id":"46613666-F248-11E8-B48F-1D18A9856A87","full_name":"Igler, Claudia"},{"last_name":"Moreno","first_name":"Anaisa","full_name":"Moreno, Anaisa"},{"full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C"},{"id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4624-4612","first_name":"Jonathan P","last_name":"Bollback","full_name":"Bollback, Jonathan P"}],"date_updated":"2021-01-12T06:50:39Z","date_created":"2018-12-11T11:51:57Z","volume":33,"month":"03","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":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425","name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7"}],"doi":"10.1093/molbev/msv269","language":[{"iso":"eng"}]},{"day":"10","scopus_import":1,"date_published":"2016-01-10T00:00:00Z","page":"173 - 191","citation":{"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","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.","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","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.","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.","short":"A. Beica, C.C. Guet, T. Petrov, in:, Springer, 2016, pp. 173–191.","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."},"abstract":[{"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.","lang":"eng"}],"alternative_title":["LNCS"],"type":"conference","oa_version":"Preprint","title":"Efficient reduction of kappa models by static inspection of the rule-set","status":"public","intvolume":" 9271","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","_id":"1524","month":"01","language":[{"iso":"eng"}],"conference":{"end_date":"2015-09-05","start_date":"2015-09-04","location":"Madrid, Spain","name":"HSB: Hybrid Systems Biology"},"doi":"10.1007/978-3-319-26916-0_10","quality_controlled":"1","project":[{"_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734","call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme"}],"oa":1,"main_file_link":[{"open_access":"1","url":"http://arxiv.org/abs/1501.00440"}],"publist_id":"5649","ec_funded":1,"date_created":"2018-12-11T11:52:31Z","date_updated":"2021-01-12T06:51:22Z","volume":9271,"author":[{"first_name":"Andreea","last_name":"Beica","full_name":"Beica, Andreea"},{"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":"Petrov, Tatjana","first_name":"Tatjana","last_name":"Petrov","id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9041-0905"}],"publication_status":"published","publisher":"Springer","department":[{"_id":"CaGu"},{"_id":"ToHe"}],"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"},{"type":"journal_article","issue":"4","abstract":[{"lang":"eng","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."}],"intvolume":" 12","status":"public","ddc":["576","579"],"title":"Genetic manipulation of glycogen allocation affects replicative lifespan in E coli","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","_id":"1250","oa_version":"Published Version","file":[{"creator":"system","content_type":"application/pdf","file_size":6273249,"file_name":"IST-2016-705-v1+1_journal.pgen.1005974.PDF","access_level":"open_access","date_created":"2018-12-12T10:14:17Z","date_updated":"2020-07-14T12:44:41Z","checksum":"53d22b2b39e5adc243d34f18b2615a85","file_id":"5067","relation":"main_file"}],"pubrep_id":"705","scopus_import":1,"has_accepted_license":"1","day":"19","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.","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","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.","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"},"publication":"PLoS Genetics","date_published":"2016-04-19T00:00:00Z","article_number":"e1005974","publist_id":"6077","file_date_updated":"2020-07-14T12:44:41Z","publisher":"Public Library of Science","department":[{"_id":"CaGu"}],"publication_status":"published","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).","volume":12,"date_created":"2018-12-11T11:50:56Z","date_updated":"2023-02-23T14:11:39Z","related_material":{"record":[{"id":"9873","status":"public","relation":"research_data"}]},"author":[{"last_name":"Boehm","first_name":"Alex","full_name":"Boehm, Alex"},{"full_name":"Arnoldini, Markus","last_name":"Arnoldini","first_name":"Markus"},{"full_name":"Bergmiller, Tobias","orcid":"0000-0001-5396-4346","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","last_name":"Bergmiller","first_name":"Tobias"},{"full_name":"Röösli, Thomas","first_name":"Thomas","last_name":"Röösli"},{"last_name":"Bigosch","first_name":"Colette","full_name":"Bigosch, Colette"},{"full_name":"Ackermann, Martin","first_name":"Martin","last_name":"Ackermann"}],"month":"04","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":"10.1371/journal.pgen.1005974"},{"day":"19","month":"04","article_processing_charge":"No","doi":"10.1371/journal.pgen.1005974.s015","citation":{"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.","short":"A. Boehm, M. Arnoldini, T. Bergmiller, T. Röösli, C. Bigosch, M. Ackermann, (2016).","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.","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","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.","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"},"type":"research_data_reference","author":[{"last_name":"Boehm","first_name":"Alex","full_name":"Boehm, Alex"},{"first_name":"Markus","last_name":"Arnoldini","full_name":"Arnoldini, Markus"},{"id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5396-4346","first_name":"Tobias","last_name":"Bergmiller","full_name":"Bergmiller, Tobias"},{"full_name":"Röösli, Thomas","first_name":"Thomas","last_name":"Röösli"},{"first_name":"Colette","last_name":"Bigosch","full_name":"Bigosch, Colette"},{"last_name":"Ackermann","first_name":"Martin","full_name":"Ackermann, Martin"}],"related_material":{"record":[{"status":"public","relation":"used_in_publication","id":"1250"}]},"date_created":"2021-08-10T09:42:34Z","date_updated":"2023-02-21T16:50:13Z","oa_version":"Published Version","_id":"9873","year":"2016","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","title":"Quantification of the growth rate reduction as a consequence of age-specific mortality","status":"public","publisher":"Public Library of Science","department":[{"_id":"CaGu"}]},{"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":{"issn":["0737-4038"],"eissn":["1537-1719"]},"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.).","year":"2016","pmid":1,"publication_status":"published","department":[{"_id":"CaGu"}],"publisher":"Oxford University Press","author":[{"last_name":"Wielgoss","first_name":"Sébastien","full_name":"Wielgoss, Sébastien"},{"last_name":"Bergmiller","first_name":"Tobias","orcid":"0000-0001-5396-4346","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","full_name":"Bergmiller, Tobias"},{"first_name":"Anna M.","last_name":"Bischofberger","full_name":"Bischofberger, Anna M."},{"full_name":"Hall, Alex R.","last_name":"Hall","first_name":"Alex R."}],"related_material":{"record":[{"id":"9719","relation":"research_data","status":"public"}]},"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/","publication":"Molecular Biology and Evolution","citation":{"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.","short":"S. Wielgoss, T. Bergmiller, A.M. Bischofberger, A.R. Hall, Molecular Biology and Evolution 33 (2016) 770–782.","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.","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","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.","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."},"page":"770-782","date_published":"2016-03-01T00:00:00Z","scopus_import":"1","day":"01","has_accepted_license":"1","article_processing_charge":"No","_id":"5749","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","ddc":["576"],"title":"Adaptation to parasites and costs of parasite resistance in mutator and nonmutator bacteria","status":"public","intvolume":" 33","pubrep_id":"587","oa_version":"Published Version","file":[{"date_updated":"2020-07-14T12:47:10Z","date_created":"2018-12-18T13:21:45Z","checksum":"47d9010690b6c5c17f2ac830cc63ac5c","file_id":"5750","relation":"main_file","creator":"dernst","file_size":634037,"content_type":"application/pdf","file_name":"2016_MolBiolEvol_Wielgoss.pdf","access_level":"open_access"}],"type":"journal_article","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"}],"issue":"3"},{"volume":59,"date_updated":"2023-09-07T11:58:33Z","date_created":"2018-12-11T11:50:06Z","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"1155"}]},"author":[{"id":"49351290-F248-11E8-B48F-1D18A9856A87","last_name":"Daca","first_name":"Przemyslaw","full_name":"Daca, Przemyslaw"},{"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","last_name":"Kretinsky","first_name":"Jan","orcid":"0000-0002-8122-2881","id":"44CEF464-F248-11E8-B48F-1D18A9856A87"},{"id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9041-0905","first_name":"Tatjana","last_name":"Petrov","full_name":"Petrov, Tatjana"}],"department":[{"_id":"ToHe"},{"_id":"KrCh"},{"_id":"CaGu"}],"publisher":"Schloss Dagstuhl - Leibniz-Zentrum für Informatik","publication_status":"published","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.","year":"2016","ec_funded":1,"publist_id":"6283","file_date_updated":"2018-12-12T10:11:39Z","article_number":"20","language":[{"iso":"eng"}],"doi":"10.4230/LIPIcs.CONCUR.2016.20","conference":{"name":"CONCUR: Concurrency Theory","start_date":"2016-08-23","location":"Quebec City; Canada","end_date":"2016-08-26"},"project":[{"_id":"25EE3708-B435-11E9-9278-68D0E5697425","grant_number":"267989","call_identifier":"FP7","name":"Quantitative Reactive Modeling"},{"_id":"25832EC2-B435-11E9-9278-68D0E5697425","grant_number":"S 11407_N23","call_identifier":"FWF","name":"Rigorous Systems Engineering"},{"_id":"25F42A32-B435-11E9-9278-68D0E5697425","grant_number":"Z211","name":"The Wittgenstein Prize","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,"month":"08","file":[{"date_updated":"2018-12-12T10:11:39Z","date_created":"2018-12-12T10:11:39Z","relation":"main_file","file_id":"4895","file_size":501827,"content_type":"application/pdf","creator":"system","file_name":"IST-2017-794-v1+1_LIPIcs-CONCUR-2016-20.pdf","access_level":"open_access"}],"oa_version":"Published Version","pubrep_id":"794","intvolume":" 59","status":"public","title":"Linear distances between Markov chains","ddc":["004"],"_id":"1093","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","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"}],"alternative_title":["LIPIcs"],"type":"conference","date_published":"2016-08-01T00:00:00Z","citation":{"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.","short":"P. Daca, T.A. Henzinger, J. Kretinsky, T. Petrov, in:, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2016.","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.","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.","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","ista":"Daca P, Henzinger TA, Kretinsky J, Petrov T. 2016. Linear distances between Markov chains. CONCUR: Concurrency Theory, LIPIcs, vol. 59, 20.","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"},"has_accepted_license":"1","day":"01","scopus_import":1},{"language":[{"iso":"eng"}],"doi":"10.1007/978-3-662-49674-9_7","conference":{"name":"TACAS: Tools and Algorithms for the Construction and Analysis of Systems","start_date":"2016-04-02","location":"Eindhoven, The Netherlands","end_date":"2016-04-08"},"project":[{"call_identifier":"FP7","name":"Quantitative Reactive Modeling","grant_number":"267989","_id":"25EE3708-B435-11E9-9278-68D0E5697425"},{"name":"Rigorous Systems Engineering","call_identifier":"FWF","grant_number":"S 11407_N23","_id":"25832EC2-B435-11E9-9278-68D0E5697425"},{"name":"The Wittgenstein Prize","call_identifier":"FWF","grant_number":"Z211","_id":"25F42A32-B435-11E9-9278-68D0E5697425"},{"grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme"}],"quality_controlled":"1","main_file_link":[{"url":"https://arxiv.org/abs/1504.05739","open_access":"1"}],"oa":1,"month":"01","volume":9636,"date_created":"2018-12-11T11:50:51Z","date_updated":"2023-09-07T11:58:33Z","related_material":{"record":[{"id":"471","status":"public","relation":"later_version"},{"id":"1155","status":"public","relation":"dissertation_contains"}]},"author":[{"last_name":"Daca","first_name":"Przemyslaw","id":"49351290-F248-11E8-B48F-1D18A9856A87","full_name":"Daca, Przemyslaw"},{"full_name":"Henzinger, Thomas A","orcid":"0000−0002−2985−7724","id":"40876CD8-F248-11E8-B48F-1D18A9856A87","last_name":"Henzinger","first_name":"Thomas A"},{"full_name":"Kretinsky, Jan","first_name":"Jan","last_name":"Kretinsky","id":"44CEF464-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8122-2881"},{"full_name":"Petrov, Tatjana","id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9041-0905","first_name":"Tatjana","last_name":"Petrov"}],"department":[{"_id":"ToHe"},{"_id":"CaGu"}],"publisher":"Springer","publication_status":"published","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","ec_funded":1,"publist_id":"6099","date_published":"2016-01-01T00:00:00Z","page":"112 - 129","citation":{"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.","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.","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","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","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.","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.","short":"P. Daca, T.A. Henzinger, J. Kretinsky, T. Petrov, in:, Springer, 2016, pp. 112–129."},"day":"01","scopus_import":1,"oa_version":"Preprint","intvolume":" 9636","title":"Faster statistical model checking for unbounded temporal properties","status":"public","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","_id":"1234","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."}],"alternative_title":["LNCS"],"type":"conference"},{"language":[{"iso":"eng"}],"doi":"10.1016/j.cub.2015.12.041","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 (DOC Fellowship)"}],"quality_controlled":"1","month":"02","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":[{"orcid":"0000-0001-7460-7479","id":"4569785E-F248-11E8-B48F-1D18A9856A87","last_name":"Pleska","first_name":"Maros","full_name":"Pleska, Maros"},{"last_name":"Qian","first_name":"Long","full_name":"Qian, Long"},{"full_name":"Okura, Reiko","first_name":"Reiko","last_name":"Okura"},{"full_name":"Bergmiller, Tobias","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5396-4346","first_name":"Tobias","last_name":"Bergmiller"},{"last_name":"Wakamoto","first_name":"Yuichi","full_name":"Wakamoto, Yuichi"},{"first_name":"Edo","last_name":"Kussell","full_name":"Kussell, Edo"},{"full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C"}],"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","publist_id":"6087","date_published":"2016-02-08T00:00:00Z","page":"404 - 409","citation":{"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.","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.","short":"M. Pleska, L. Qian, R. Okura, T. Bergmiller, Y. Wakamoto, E. Kussell, C.C. Guet, Current Biology 26 (2016) 404–409.","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.","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","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.","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"},"publication":"Current Biology","day":"08","scopus_import":1,"oa_version":"None","intvolume":" 26","status":"public","title":"Bacterial autoimmunity due to a restriction-modification system","_id":"1243","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","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."}],"type":"journal_article"},{"month":"08","language":[{"iso":"eng"}],"doi":"10.1038/ncomms12307","quality_controlled":"1","project":[{"call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734"},{"name":"Limits to selection in biology and in evolutionary computation","call_identifier":"FP7","grant_number":"250152","_id":"25B07788-B435-11E9-9278-68D0E5697425"},{"name":"Biophysics of information processing in gene regulation","call_identifier":"FWF","grant_number":"P28844-B27","_id":"254E9036-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,"file_date_updated":"2020-07-14T12:44:46Z","ec_funded":1,"publist_id":"5887","article_number":"12307","date_updated":"2023-09-07T12:53:49Z","date_created":"2018-12-11T11:51:34Z","volume":7,"author":[{"full_name":"Friedlander, Tamar","first_name":"Tamar","last_name":"Friedlander","id":"36A5845C-F248-11E8-B48F-1D18A9856A87"},{"id":"4456104E-F248-11E8-B48F-1D18A9856A87","last_name":"Prizak","first_name":"Roshan","full_name":"Prizak, Roshan"},{"full_name":"Guet, Calin C","last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Nicholas H","last_name":"Barton","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8548-5240","full_name":"Barton, Nicholas H"},{"first_name":"Gasper","last_name":"Tkacik","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","full_name":"Tkacik, Gasper"}],"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"6071"}]},"publication_status":"published","department":[{"_id":"GaTk"},{"_id":"NiBa"},{"_id":"CaGu"}],"publisher":"Nature Publishing Group","year":"2016","day":"04","has_accepted_license":"1","scopus_import":1,"date_published":"2016-08-04T00:00:00Z","publication":"Nature Communications","citation":{"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.","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.","short":"T. Friedlander, R. Prizak, C.C. Guet, N.H. Barton, G. Tkačik, Nature Communications 7 (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.","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.","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"},"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."}],"type":"journal_article","oa_version":"Published Version","file":[{"content_type":"application/pdf","file_size":861805,"creator":"system","file_name":"IST-2016-627-v1+1_ncomms12307.pdf","access_level":"open_access","date_created":"2018-12-12T10:12:01Z","date_updated":"2020-07-14T12:44:46Z","checksum":"fe3f3a1526d180b29fe691ab11435b78","relation":"main_file","file_id":"4919"},{"checksum":"164864a1a675f3ad80e9917c27aba07f","date_created":"2018-12-12T10:12:02Z","date_updated":"2020-07-14T12:44:46Z","file_id":"4920","relation":"main_file","creator":"system","file_size":1084703,"content_type":"application/pdf","access_level":"open_access","file_name":"IST-2016-627-v1+2_ncomms12307-s1.pdf"}],"pubrep_id":"627","status":"public","title":"Intrinsic limits to gene regulation by global crosstalk","ddc":["576"],"intvolume":" 7","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","_id":"1358"},{"language":[{"iso":"eng"}],"date_published":"2015-07-11T00:00:00Z","doi":"10.1145/2739480.2754758","conference":{"start_date":"2015-07-11","location":"Madrid, Spain","end_date":"2015-07-15","name":"GECCO: Genetic and evolutionary computation conference"},"project":[{"call_identifier":"FP7","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","grant_number":"618091","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425"}],"page":"1455 - 1462","quality_controlled":"1","citation":{"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.","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.","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","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","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.","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."},"oa":1,"main_file_link":[{"url":"http://arxiv.org/abs/1504.06260","open_access":"1"}],"publication":"Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation","day":"11","month":"07","scopus_import":1,"oa_version":"Preprint","date_updated":"2021-01-12T06:50:41Z","date_created":"2018-12-11T11:51:58Z","author":[{"orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","last_name":"Paixao","first_name":"Tiago","full_name":"Paixao, Tiago"},{"first_name":"Dirk","last_name":"Sudholt","full_name":"Sudholt, Dirk"},{"full_name":"Heredia, Jorge","first_name":"Jorge","last_name":"Heredia"},{"last_name":"Trubenova","first_name":"Barbora","orcid":"0000-0002-6873-2967","id":"42302D54-F248-11E8-B48F-1D18A9856A87","full_name":"Trubenova, Barbora"}],"department":[{"_id":"NiBa"},{"_id":"CaGu"}],"publisher":"ACM","publication_status":"published","status":"public","title":"First steps towards a runtime comparison of natural and artificial evolution","_id":"1430","year":"2015","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ec_funded":1,"publist_id":"5768","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 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.","lang":"eng"}],"type":"conference"},{"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","ec_funded":1,"publist_id":"5629","file_date_updated":"2020-07-14T12:45:01Z","publisher":"Elsevier","department":[{"_id":"NiBa"},{"_id":"CaGu"}],"publication_status":"published","year":"2015","volume":383,"date_created":"2018-12-11T11:52:37Z","date_updated":"2021-01-12T06:51:29Z","author":[{"full_name":"Paixao, Tiago","last_name":"Paixao","first_name":"Tiago","orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Golnaz","last_name":"Badkobeh","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"},{"last_name":"Çörüş","first_name":"Doğan","full_name":"Çörüş, Doğan"},{"last_name":"Dang","first_name":"Duccuong","full_name":"Dang, Duccuong"},{"first_name":"Tobias","last_name":"Friedrich","full_name":"Friedrich, Tobias"},{"full_name":"Lehre, Per","first_name":"Per","last_name":"Lehre"},{"full_name":"Sudholt, Dirk","last_name":"Sudholt","first_name":"Dirk"},{"last_name":"Sutton","first_name":"Andrew","full_name":"Sutton, Andrew"},{"full_name":"Trubenova, Barbora","id":"42302D54-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6873-2967","first_name":"Barbora","last_name":"Trubenova"}],"month":"10","project":[{"_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","grant_number":"618091","call_identifier":"FP7","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation"},{"name":"Limits to selection in biology and in evolutionary computation","call_identifier":"FP7","grant_number":"250152","_id":"25B07788-B435-11E9-9278-68D0E5697425"}],"quality_controlled":"1","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"},"language":[{"iso":"eng"}],"doi":"10.1016/j.jtbi.2015.07.011","type":"journal_article","abstract":[{"lang":"eng","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. "}],"intvolume":" 383","ddc":["570"],"status":"public","title":"Toward a unifying framework for evolutionary processes","_id":"1542","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Published Version","file":[{"access_level":"open_access","file_name":"IST-2016-483-v1+1_1-s2.0-S0022519315003409-main.pdf","file_size":595307,"content_type":"application/pdf","creator":"system","relation":"main_file","file_id":"5244","checksum":"33b60ecfea60764756a9ee9df5eb65ca","date_created":"2018-12-12T10:16:53Z","date_updated":"2020-07-14T12:45:01Z"}],"pubrep_id":"483","scopus_import":1,"has_accepted_license":"1","day":"21","page":"28 - 43","citation":{"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.","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.","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.","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","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.","ieee":"T. Paixao et al., “Toward a unifying framework for evolutionary processes,” Journal of Theoretical Biology, vol. 383. Elsevier, pp. 28–43, 2015.","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"},"publication":" Journal of Theoretical Biology","date_published":"2015-10-21T00:00:00Z"},{"publication_status":"published","department":[{"_id":"CaGu"},{"_id":"ToHe"}],"publisher":"IEEE","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","date_updated":"2021-01-12T06:53:33Z","date_created":"2018-12-11T11:54:18Z","volume":60,"author":[{"full_name":"Geiger, Bernhard","first_name":"Bernhard","last_name":"Geiger"},{"id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9041-0905","first_name":"Tatjana","last_name":"Petrov","full_name":"Petrov, Tatjana"},{"full_name":"Kubin, Gernot","last_name":"Kubin","first_name":"Gernot"},{"full_name":"Koeppl, Heinz","last_name":"Koeppl","first_name":"Heinz"}],"publist_id":"5262","quality_controlled":"1","oa":1,"main_file_link":[{"url":"http://arxiv.org/abs/1304.6603","open_access":"1"}],"language":[{"iso":"eng"}],"doi":"10.1109/TAC.2014.2364971","month":"04","publication_identifier":{"issn":["0018-9286"]},"title":"Optimal Kullback-Leibler aggregation via information bottleneck","status":"public","intvolume":" 60","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"1840","oa_version":"Preprint","type":"journal_article","abstract":[{"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.","lang":"eng"}],"issue":"4","page":"1010 - 1022","publication":"IEEE Transactions on Automatic Control","citation":{"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","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.","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.","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."},"date_published":"2015-04-01T00:00:00Z","scopus_import":1,"day":"01"},{"_id":"9712","year":"2015","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","department":[{"_id":"NiBa"},{"_id":"CaGu"},{"_id":"GaTk"}],"publisher":"Public Library of Science","status":"public","title":"Other fitness models for comparison & for interacting TFBSs","related_material":{"record":[{"id":"1666","relation":"used_in_publication","status":"public"}]},"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","first_name":"Tiago","last_name":"Paixao","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2361-3953"},{"full_name":"Barton, Nicholas H","last_name":"Barton","first_name":"Nicholas H","orcid":"0000-0002-8548-5240","id":"4880FE40-F248-11E8-B48F-1D18A9856A87"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","first_name":"Gašper","last_name":"Tkačik","full_name":"Tkačik, Gašper"}],"oa_version":"Published Version","date_updated":"2023-02-23T10:09:08Z","date_created":"2021-07-23T12:00:37Z","type":"research_data_reference","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.","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.","short":"M. Tugrul, T. Paixao, N.H. Barton, G. Tkačik, (2015).","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.","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","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"},"doi":"10.1371/journal.pgen.1005639.s001","date_published":"2015-11-06T00:00:00Z","article_processing_charge":"No","day":"06","month":"11"},{"title":"Data from: Adaptation to parasites and costs of parasite resistance in mutator and non-mutator bacteria","status":"public","department":[{"_id":"CaGu"}],"publisher":"Dryad","_id":"9719","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","year":"2015","date_created":"2021-07-26T08:44:04Z","date_updated":"2023-09-05T13:46:04Z","oa_version":"Published Version","author":[{"full_name":"Wielgoss, Sébastien","last_name":"Wielgoss","first_name":"Sébastien"},{"full_name":"Bergmiller, Tobias","orcid":"0000-0001-5396-4346","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","last_name":"Bergmiller","first_name":"Tobias"},{"full_name":"Bischofberger, Anna M.","first_name":"Anna M.","last_name":"Bischofberger"},{"full_name":"Hall, Alex R.","first_name":"Alex R.","last_name":"Hall"}],"related_material":{"record":[{"status":"public","relation":"used_in_publication","id":"5749"}]},"type":"research_data_reference","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."}],"citation":{"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.","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).","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.","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","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.","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"},"main_file_link":[{"url":"https://doi.org/10.5061/dryad.cj910","open_access":"1"}],"oa":1,"date_published":"2015-12-21T00:00:00Z","doi":"10.5061/dryad.cj910","month":"12","day":"21","article_processing_charge":"No"},{"publist_id":"5483","ec_funded":1,"file_date_updated":"2020-07-14T12:45:10Z","department":[{"_id":"NiBa"},{"_id":"CaGu"},{"_id":"GaTk"}],"publisher":"Public Library of Science","publication_status":"published","year":"2015","volume":11,"date_created":"2018-12-11T11:53:21Z","date_updated":"2023-09-07T11:53:49Z","related_material":{"record":[{"relation":"research_data","status":"public","id":"9712"},{"id":"1131","relation":"dissertation_contains","status":"public"}]},"author":[{"first_name":"Murat","last_name":"Tugrul","id":"37C323C6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8523-0758","full_name":"Tugrul, Murat"},{"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","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8548-5240","first_name":"Nicholas H","last_name":"Barton"},{"orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","last_name":"Tkacik","first_name":"Gasper","full_name":"Tkacik, Gasper"}],"month":"11","project":[{"grant_number":"250152","_id":"25B07788-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"Limits to selection in biology and in evolutionary computation"}],"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.pgen.1005639","type":"journal_article","issue":"11","abstract":[{"lang":"eng","text":"Evolution of gene regulation is crucial for our understanding of the phenotypic differences between species, populations and individuals. Sequence-specific binding of transcription factors to the regulatory regions on the DNA is a key regulatory mechanism that determines gene expression and hence heritable phenotypic variation. We use a biophysical model for directional selection on gene expression to estimate the rates of gain and loss of transcription factor binding sites (TFBS) in finite populations under both point and insertion/deletion mutations. Our results show that these rates are typically slow for a single TFBS in an isolated DNA region, unless the selection is extremely strong. These rates decrease drastically with increasing TFBS length or increasingly specific protein-DNA interactions, making the evolution of sites longer than ∼ 10 bp unlikely on typical eukaryotic speciation timescales. Similarly, evolution converges to the stationary distribution of binding sequences very slowly, making the equilibrium assumption questionable. The availability of longer regulatory sequences in which multiple binding sites can evolve simultaneously, the presence of “pre-sites” or partially decayed old sites in the initial sequence, and biophysical cooperativity between transcription factors, can all facilitate gain of TFBS and reconcile theoretical calculations with timescales inferred from comparative genomics."}],"intvolume":" 11","title":"Dynamics of transcription factor binding site evolution","status":"public","ddc":["576"],"_id":"1666","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file":[{"file_id":"4657","relation":"main_file","checksum":"a4e72fca5ccf40ddacf4d08c8e46b554","date_updated":"2020-07-14T12:45:10Z","date_created":"2018-12-12T10:07:58Z","access_level":"open_access","file_name":"IST-2016-463-v1+1_journal.pgen.1005639.pdf","creator":"system","content_type":"application/pdf","file_size":2580778}],"oa_version":"Published Version","pubrep_id":"463","scopus_import":1,"has_accepted_license":"1","day":"06","citation":{"short":"M. Tugrul, T. Paixao, N.H. Barton, G. Tkačik, PLoS Genetics 11 (2015).","mla":"Tugrul, Murat, et al. “Dynamics of Transcription Factor Binding Site Evolution.” PLoS Genetics, vol. 11, no. 11, Public Library of Science, 2015, doi:10.1371/journal.pgen.1005639.","chicago":"Tugrul, Murat, Tiago Paixao, Nicholas H Barton, and Gašper Tkačik. “Dynamics of Transcription Factor Binding Site Evolution.” PLoS Genetics. Public Library of Science, 2015. https://doi.org/10.1371/journal.pgen.1005639.","ama":"Tugrul M, Paixao T, Barton NH, Tkačik G. Dynamics of transcription factor binding site evolution. PLoS Genetics. 2015;11(11). doi:10.1371/journal.pgen.1005639","ieee":"M. Tugrul, T. Paixao, N. H. Barton, and G. Tkačik, “Dynamics of transcription factor binding site evolution,” PLoS Genetics, vol. 11, no. 11. Public Library of Science, 2015.","apa":"Tugrul, M., Paixao, T., Barton, N. H., & Tkačik, G. (2015). Dynamics of transcription factor binding site evolution. PLoS Genetics. Public Library of Science. https://doi.org/10.1371/journal.pgen.1005639","ista":"Tugrul M, Paixao T, Barton NH, Tkačik G. 2015. Dynamics of transcription factor binding site evolution. PLoS Genetics. 11(11)."},"publication":"PLoS Genetics","date_published":"2015-11-06T00:00:00Z"},{"main_file_link":[{"open_access":"1","url":"http://arxiv.org/abs/1410.7704"}],"oa":1,"project":[{"call_identifier":"FP7","name":"Quantitative Reactive Modeling","_id":"25EE3708-B435-11E9-9278-68D0E5697425","grant_number":"267989"},{"grant_number":"S 11407_N23","_id":"25832EC2-B435-11E9-9278-68D0E5697425","name":"Rigorous Systems Engineering","call_identifier":"FWF"},{"_id":"25F42A32-B435-11E9-9278-68D0E5697425","grant_number":"Z211","call_identifier":"FWF","name":"The Wittgenstein Prize"},{"_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","grant_number":"618091","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","call_identifier":"FP7"},{"_id":"25B07788-B435-11E9-9278-68D0E5697425","grant_number":"250152","call_identifier":"FP7","name":"Limits to selection in biology and in evolutionary computation"},{"grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425","name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7"}],"quality_controlled":"1","doi":"10.1007/978-3-662-46681-0_47","conference":{"end_date":"2015-04-18","location":"London, United Kingdom","start_date":"2015-04-11","name":"TACAS: Tools and Algorithms for the Construction and Analysis of Systems"},"language":[{"iso":"eng"}],"month":"04","year":"2015","acknowledgement":"SNSF Early Postdoc.Mobility Fellowship, the grant number P2EZP2 148797.\r\n","publisher":"Springer","department":[{"_id":"ToHe"},{"_id":"CaGu"},{"_id":"NiBa"}],"publication_status":"published","related_material":{"record":[{"status":"public","relation":"later_version","id":"1351"}]},"author":[{"last_name":"Giacobbe","first_name":"Mirco","orcid":"0000-0001-8180-0904","id":"3444EA5E-F248-11E8-B48F-1D18A9856A87","full_name":"Giacobbe, Mirco"},{"first_name":"Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C"},{"full_name":"Gupta, Ashutosh","first_name":"Ashutosh","last_name":"Gupta","id":"335E5684-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Henzinger","first_name":"Thomas A","orcid":"0000−0002−2985−7724","id":"40876CD8-F248-11E8-B48F-1D18A9856A87","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"},{"first_name":"Tatjana","last_name":"Petrov","id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9041-0905","full_name":"Petrov, Tatjana"}],"volume":9035,"date_updated":"2023-09-20T11:06:03Z","date_created":"2018-12-11T11:54:16Z","publist_id":"5267","ec_funded":1,"citation":{"ama":"Giacobbe M, Guet CC, Gupta A, Henzinger TA, Paixao T, Petrov T. Model checking gene regulatory networks. 2015;9035:469-483. doi:10.1007/978-3-662-46681-0_47","apa":"Giacobbe, M., Guet, C. C., Gupta, A., Henzinger, T. A., Paixao, T., & Petrov, T. (2015). Model checking gene regulatory networks. Presented at the TACAS: Tools and Algorithms for the Construction and Analysis of Systems, London, United Kingdom: Springer. https://doi.org/10.1007/978-3-662-46681-0_47","ieee":"M. Giacobbe, C. C. Guet, A. Gupta, T. A. Henzinger, T. Paixao, and T. Petrov, “Model checking gene regulatory networks,” vol. 9035. Springer, pp. 469–483, 2015.","ista":"Giacobbe M, Guet CC, Gupta A, Henzinger TA, Paixao T, Petrov T. 2015. Model checking gene regulatory networks. 9035, 469–483.","short":"M. Giacobbe, C.C. Guet, A. Gupta, T.A. Henzinger, T. Paixao, T. Petrov, 9035 (2015) 469–483.","mla":"Giacobbe, Mirco, et al. Model Checking Gene Regulatory Networks. Vol. 9035, Springer, 2015, pp. 469–83, doi:10.1007/978-3-662-46681-0_47.","chicago":"Giacobbe, Mirco, Calin C Guet, Ashutosh Gupta, Thomas A Henzinger, Tiago Paixao, and Tatjana Petrov. “Model Checking Gene Regulatory Networks.” Lecture Notes in Computer Science. Springer, 2015. https://doi.org/10.1007/978-3-662-46681-0_47."},"page":"469 - 483","date_published":"2015-04-01T00:00:00Z","scopus_import":1,"series_title":"Lecture Notes in Computer Science","day":"01","_id":"1835","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":" 9035","title":"Model checking gene regulatory networks","status":"public","oa_version":"Preprint","type":"conference","alternative_title":["LNCS"],"abstract":[{"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 logics. 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.","lang":"eng"}]},{"pubrep_id":"438","oa_version":"Published Version","file":[{"access_level":"open_access","file_name":"IST-2016-438-v1+1_journal.pone.0106247.pdf","content_type":"application/pdf","file_size":4248801,"creator":"system","relation":"main_file","file_id":"5205","checksum":"7d02c3da7f72b82bb5d7932d80c3251f","date_updated":"2020-07-14T12:45:20Z","date_created":"2018-12-12T10:16:19Z"}],"_id":"1894","user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","intvolume":" 9","ddc":["570"],"status":"public","title":"Functional and bioinformatics analysis of two Campylobacter jejuni homologs of the thiol-disulfide oxidoreductase, DsbA","issue":"9","abstract":[{"lang":"eng","text":"Background: Bacterial Dsb enzymes are involved in the oxidative folding of many proteins, through the formation of disulfide bonds between their cysteine residues. The Dsb protein network has been well characterized in cells of the model microorganism Escherichia coli. To gain insight into the functioning of the Dsb system in epsilon-Proteobacteria, where it plays an important role in the colonization process, we studied two homologs of the main Escherichia coli Dsb oxidase (EcDsbA) that are present in the cells of the enteric pathogen Campylobacter jejuni, the most frequently reported bacterial cause of human enteritis in the world. Methods and Results: Phylogenetic analysis suggests the horizontal transfer of the epsilon-Proteobacterial DsbAs from a common ancestor to gamma-Proteobacteria, which then gave rise to the DsbL lineage. Phenotype and enzymatic assays suggest that the two C. jejuni DsbAs play different roles in bacterial cells and have divergent substrate spectra. CjDsbA1 is essential for the motility and autoagglutination phenotypes, while CjDsbA2 has no impact on those processes. CjDsbA1 plays a critical role in the oxidative folding that ensures the activity of alkaline phosphatase CjPhoX, whereas CjDsbA2 is crucial for the activity of arylsulfotransferase CjAstA, encoded within the dsbA2-dsbB-astA operon. Conclusions: Our results show that CjDsbA1 is the primary thiol-oxidoreductase affecting life processes associated with bacterial spread and host colonization, as well as ensuring the oxidative folding of particular protein substrates. In contrast, CjDsbA2 activity does not affect the same processes and so far its oxidative folding activity has been demonstrated for one substrate, arylsulfotransferase CjAstA. The results suggest the cooperation between CjDsbA2 and CjDsbB. In the case of the CjDsbA1, this cooperation is not exclusive and there is probably another protein to be identified in C. jejuni cells that acts to re-oxidize CjDsbA1. Altogether the data presented here constitute the considerable insight to the Epsilonproteobacterial Dsb systems, which have been poorly understood so far."}],"type":"journal_article","date_published":"2014-09-02T00:00:00Z","citation":{"ieee":"A. Grabowska et al., “Functional and bioinformatics analysis of two Campylobacter jejuni homologs of the thiol-disulfide oxidoreductase, DsbA,” PLoS One, vol. 9, no. 9. Public Library of Science, 2014.","apa":"Grabowska, A., Wywiał, E., Dunin Horkawicz, S., Łasica, A., Wösten, M., Nagy-Staron, A. A., … Jagusztyn Krynicka, E. (2014). Functional and bioinformatics analysis of two Campylobacter jejuni homologs of the thiol-disulfide oxidoreductase, DsbA. PLoS One. Public Library of Science. https://doi.org/10.1371/journal.pone.0106247","ista":"Grabowska A, Wywiał E, Dunin Horkawicz S, Łasica A, Wösten M, Nagy-Staron AA, Godlewska R, Bocian Ostrzycka K, Pieńkowska K, Łaniewski P, Bujnicki J, Van Putten J, Jagusztyn Krynicka E. 2014. Functional and bioinformatics analysis of two Campylobacter jejuni homologs of the thiol-disulfide oxidoreductase, DsbA. PLoS One. 9(9), e106247.","ama":"Grabowska A, Wywiał E, Dunin Horkawicz S, et al. Functional and bioinformatics analysis of two Campylobacter jejuni homologs of the thiol-disulfide oxidoreductase, DsbA. PLoS One. 2014;9(9). doi:10.1371/journal.pone.0106247","chicago":"Grabowska, Anna, Ewa Wywiał, Stanislaw Dunin Horkawicz, Anna Łasica, Marc Wösten, Anna A Nagy-Staron, Renata Godlewska, et al. “Functional and Bioinformatics Analysis of Two Campylobacter Jejuni Homologs of the Thiol-Disulfide Oxidoreductase, DsbA.” PLoS One. Public Library of Science, 2014. https://doi.org/10.1371/journal.pone.0106247.","short":"A. Grabowska, E. Wywiał, S. Dunin Horkawicz, A. Łasica, M. Wösten, A.A. Nagy-Staron, R. Godlewska, K. Bocian Ostrzycka, K. Pieńkowska, P. Łaniewski, J. Bujnicki, J. Van Putten, E. Jagusztyn Krynicka, PLoS One 9 (2014).","mla":"Grabowska, Anna, et al. “Functional and Bioinformatics Analysis of Two Campylobacter Jejuni Homologs of the Thiol-Disulfide Oxidoreductase, DsbA.” PLoS One, vol. 9, no. 9, e106247, Public Library of Science, 2014, doi:10.1371/journal.pone.0106247."},"publication":"PLoS One","has_accepted_license":"1","day":"02","scopus_import":1,"author":[{"first_name":"Anna","last_name":"Grabowska","full_name":"Grabowska, Anna"},{"full_name":"Wywiał, Ewa","first_name":"Ewa","last_name":"Wywiał"},{"last_name":"Dunin Horkawicz","first_name":"Stanislaw","full_name":"Dunin Horkawicz, Stanislaw"},{"last_name":"Łasica","first_name":"Anna","full_name":"Łasica, Anna"},{"full_name":"Wösten, Marc","last_name":"Wösten","first_name":"Marc"},{"full_name":"Nagy-Staron, Anna A","id":"3ABC5BA6-F248-11E8-B48F-1D18A9856A87","first_name":"Anna A","last_name":"Nagy-Staron"},{"last_name":"Godlewska","first_name":"Renata","full_name":"Godlewska, Renata"},{"full_name":"Bocian Ostrzycka, Katarzyna","last_name":"Bocian Ostrzycka","first_name":"Katarzyna"},{"last_name":"Pieńkowska","first_name":"Katarzyna","full_name":"Pieńkowska, Katarzyna"},{"full_name":"Łaniewski, Paweł","first_name":"Paweł","last_name":"Łaniewski"},{"first_name":"Janusz","last_name":"Bujnicki","full_name":"Bujnicki, Janusz"},{"last_name":"Van Putten","first_name":"Jos","full_name":"Van Putten, Jos"},{"last_name":"Jagusztyn Krynicka","first_name":"Elzbieta","full_name":"Jagusztyn Krynicka, Elzbieta"}],"volume":9,"date_updated":"2021-01-12T06:53:54Z","date_created":"2018-12-11T11:54:35Z","year":"2014","publisher":"Public Library of Science","department":[{"_id":"CaGu"}],"publication_status":"published","publist_id":"5201","file_date_updated":"2020-07-14T12:45:20Z","article_number":"e106247","doi":"10.1371/journal.pone.0106247","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"},"quality_controlled":"1","month":"09"},{"scopus_import":1,"day":"20","page":"767 - 797","citation":{"chicago":"Ganguly, Arnab, Tatjana Petrov, and Heinz Koeppl. “Markov Chain Aggregation and Its Applications to Combinatorial Reaction Networks.” Journal of Mathematical Biology. Springer, 2014. https://doi.org/10.1007/s00285-013-0738-7.","short":"A. Ganguly, T. Petrov, H. Koeppl, Journal of Mathematical Biology 69 (2014) 767–797.","mla":"Ganguly, Arnab, et al. “Markov Chain Aggregation and Its Applications to Combinatorial Reaction Networks.” Journal of Mathematical Biology, vol. 69, no. 3, Springer, 2014, pp. 767–97, doi:10.1007/s00285-013-0738-7.","apa":"Ganguly, A., Petrov, T., & Koeppl, H. (2014). Markov chain aggregation and its applications to combinatorial reaction networks. Journal of Mathematical Biology. Springer. https://doi.org/10.1007/s00285-013-0738-7","ieee":"A. Ganguly, T. Petrov, and H. Koeppl, “Markov chain aggregation and its applications to combinatorial reaction networks,” Journal of Mathematical Biology, vol. 69, no. 3. Springer, pp. 767–797, 2014.","ista":"Ganguly A, Petrov T, Koeppl H. 2014. Markov chain aggregation and its applications to combinatorial reaction networks. Journal of Mathematical Biology. 69(3), 767–797.","ama":"Ganguly A, Petrov T, Koeppl H. Markov chain aggregation and its applications to combinatorial reaction networks. Journal of Mathematical Biology. 2014;69(3):767-797. doi:10.1007/s00285-013-0738-7"},"publication":"Journal of Mathematical Biology","date_published":"2014-11-20T00:00:00Z","type":"journal_article","issue":"3","abstract":[{"text":"We consider a continuous-time Markov chain (CTMC) whose state space is partitioned into aggregates, and each aggregate is assigned a probability measure. A sufficient condition for defining a CTMC over the aggregates is presented as a variant of weak lumpability, which also characterizes that the measure over the original process can be recovered from that of the aggregated one. We show how the applicability of de-aggregation depends on the initial distribution. The application section is devoted to illustrate how the developed theory aids in reducing CTMC models of biochemical systems particularly in connection to protein-protein interactions. We assume that the model is written by a biologist in form of site-graph-rewrite rules. Site-graph-rewrite rules compactly express that, often, only a local context of a protein (instead of a full molecular species) needs to be in a certain configuration in order to trigger a reaction event. This observation leads to suitable aggregate Markov chains with smaller state spaces, thereby providing sufficient reduction in computational complexity. This is further exemplified in two case studies: simple unbounded polymerization and early EGFR/insulin crosstalk.","lang":"eng"}],"intvolume":" 69","status":"public","title":"Markov chain aggregation and its applications to combinatorial reaction networks","_id":"2056","user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","oa_version":"Submitted Version","month":"11","quality_controlled":"1","oa":1,"main_file_link":[{"open_access":"1","url":"http://arxiv.org/abs/1303.4532"}],"language":[{"iso":"eng"}],"doi":"10.1007/s00285-013-0738-7","publist_id":"4990","department":[{"_id":"CaGu"},{"_id":"ToHe"}],"publisher":"Springer","publication_status":"published","year":"2014","acknowledgement":"T. Petrov is supported by SystemsX.ch—the Swiss Inititative for Systems Biology.","volume":69,"date_updated":"2021-01-12T06:55:01Z","date_created":"2018-12-11T11:55:28Z","author":[{"last_name":"Ganguly","first_name":"Arnab","full_name":"Ganguly, Arnab"},{"full_name":"Petrov, Tatjana","orcid":"0000-0002-9041-0905","id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","last_name":"Petrov","first_name":"Tatjana"},{"last_name":"Koeppl","first_name":"Heinz","full_name":"Koeppl, Heinz"}]},{"publist_id":"4954","file_date_updated":"2020-07-14T12:45:28Z","year":"2014","acknowledgement":"The authors are grateful to the Leverhulme Trust (F/00 215/AW) for funding this work.","publisher":"Wiley","department":[{"_id":"CaGu"}],"publication_status":"published","related_material":{"record":[{"id":"9747","status":"public","relation":"research_data"}]},"author":[{"last_name":"Lagator","first_name":"Mato","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","full_name":"Lagator, Mato"},{"first_name":"Andrew","last_name":"Morgan","full_name":"Morgan, Andrew"},{"first_name":"Paul","last_name":"Neve","full_name":"Neve, Paul"},{"full_name":"Colegrave, Nick","last_name":"Colegrave","first_name":"Nick"}],"volume":68,"date_created":"2018-12-11T11:55:36Z","date_updated":"2023-02-23T14:06:51Z","month":"04","oa":1,"quality_controlled":"1","doi":"10.1111/evo.12440","language":[{"iso":"eng"}],"type":"journal_article","issue":"8","abstract":[{"lang":"eng","text":"Understanding the effects of sex and migration on adaptation to novel environments remains a key problem in evolutionary biology. Using a single-cell alga Chlamydomonas reinhardtii, we investigated how sex and migration affected rates of evolutionary rescue in a sink environment, and subsequent changes in fitness following evolutionary rescue. We show that sex and migration affect both the rate of evolutionary rescue and subsequent adaptation. However, their combined effects change as the populations adapt to a sink habitat. Both sex and migration independently increased rates of evolutionary rescue, but the effect of sex on subsequent fitness improvements, following initial rescue, changed with migration, as sex was beneficial in the absence of migration but constraining adaptation when combined with migration. These results suggest that sex and migration are beneficial during the initial stages of adaptation, but can become detrimental as the population adapts to its environment."}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"2083","intvolume":" 68","title":"Role of sex and migration in adaptation to sink environments","ddc":["570"],"status":"public","file":[{"creator":"dernst","file_size":467254,"content_type":"application/pdf","access_level":"open_access","file_name":"2014_Evolution_Lagator.pdf","checksum":"8d459b07e4a11bb5fde92d969184fe48","date_created":"2020-05-14T16:40:31Z","date_updated":"2020-07-14T12:45:28Z","file_id":"7845","relation":"main_file"}],"oa_version":"Published Version","scopus_import":1,"has_accepted_license":"1","article_processing_charge":"No","day":"25","citation":{"ieee":"M. Lagator, A. Morgan, P. Neve, and N. Colegrave, “Role of sex and migration in adaptation to sink environments,” Evolution, vol. 68, no. 8. Wiley, pp. 2296–2305, 2014.","apa":"Lagator, M., Morgan, A., Neve, P., & Colegrave, N. (2014). Role of sex and migration in adaptation to sink environments. Evolution. Wiley. https://doi.org/10.1111/evo.12440","ista":"Lagator M, Morgan A, Neve P, Colegrave N. 2014. Role of sex and migration in adaptation to sink environments. Evolution. 68(8), 2296–2305.","ama":"Lagator M, Morgan A, Neve P, Colegrave N. Role of sex and migration in adaptation to sink environments. Evolution. 2014;68(8):2296-2305. doi:10.1111/evo.12440","chicago":"Lagator, Mato, Andrew Morgan, Paul Neve, and Nick Colegrave. “Role of Sex and Migration in Adaptation to Sink Environments.” Evolution. Wiley, 2014. https://doi.org/10.1111/evo.12440.","short":"M. Lagator, A. Morgan, P. Neve, N. Colegrave, Evolution 68 (2014) 2296–2305.","mla":"Lagator, Mato, et al. “Role of Sex and Migration in Adaptation to Sink Environments.” Evolution, vol. 68, no. 8, Wiley, 2014, pp. 2296–305, doi:10.1111/evo.12440."},"publication":"Evolution","page":"2296 - 2305","article_type":"original","date_published":"2014-04-25T00:00:00Z"},{"article_processing_charge":"No","month":"04","day":"17","date_published":"2014-04-17T00:00:00Z","doi":"10.5061/dryad.s42n1","oa":1,"main_file_link":[{"url":"https://doi.org/10.5061/dryad.s42n1","open_access":"1"}],"citation":{"apa":"Lagator, M., Morgan, A., Neve, P., & Colegrave, N. (2014). Data from: Role of sex and migration in adaptation to sink environments. Dryad. https://doi.org/10.5061/dryad.s42n1","ieee":"M. Lagator, A. Morgan, P. Neve, and N. Colegrave, “Data from: Role of sex and migration in adaptation to sink environments.” Dryad, 2014.","ista":"Lagator M, Morgan A, Neve P, Colegrave N. 2014. Data from: Role of sex and migration in adaptation to sink environments, Dryad, 10.5061/dryad.s42n1.","ama":"Lagator M, Morgan A, Neve P, Colegrave N. Data from: Role of sex and migration in adaptation to sink environments. 2014. doi:10.5061/dryad.s42n1","chicago":"Lagator, Mato, Andrew Morgan, Paul Neve, and Nick Colegrave. “Data from: Role of Sex and Migration in Adaptation to Sink Environments.” Dryad, 2014. https://doi.org/10.5061/dryad.s42n1.","short":"M. Lagator, A. Morgan, P. Neve, N. Colegrave, (2014).","mla":"Lagator, Mato, et al. Data from: Role of Sex and Migration in Adaptation to Sink Environments. Dryad, 2014, doi:10.5061/dryad.s42n1."},"abstract":[{"lang":"eng","text":"Understanding the effects of sex and migration on adaptation to novel environments remains a key problem in evolutionary biology. Using a single-cell alga Chlamydomonas reinhardtii, we investigated how sex and migration affected rates of evolutionary rescue in a sink environment, and subsequent changes in fitness following evolutionary rescue. We show that sex and migration affect both the rate of evolutionary rescue and subsequent adaptation. However, their combined effects change as the populations adapt to a sink habitat. Both sex and migration independently increased rates of evolutionary rescue, but the effect of sex on subsequent fitness improvements, following initial rescue, changed with migration, as sex was beneficial in the absence of migration but constraining adaptation when combined with migration. These results suggest that sex and migration are beneficial during the initial stages of adaptation, but can become detrimental as the population adapts to its environment."}],"type":"research_data_reference","related_material":{"record":[{"relation":"used_in_publication","status":"public","id":"2083"}]},"author":[{"id":"345D25EC-F248-11E8-B48F-1D18A9856A87","first_name":"Mato","last_name":"Lagator","full_name":"Lagator, Mato"},{"full_name":"Morgan, Andrew","last_name":"Morgan","first_name":"Andrew"},{"last_name":"Neve","first_name":"Paul","full_name":"Neve, Paul"},{"full_name":"Colegrave, Nick","last_name":"Colegrave","first_name":"Nick"}],"oa_version":"Published Version","date_created":"2021-07-28T15:32:55Z","date_updated":"2023-02-23T10:27:31Z","_id":"9747","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","year":"2014","publisher":"Dryad","department":[{"_id":"CaGu"}],"title":"Data from: Role of sex and migration in adaptation to sink environments","status":"public"},{"doi":"10.1098/rspb.2014.1679","language":[{"iso":"eng"}],"main_file_link":[{"url":"http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4211454/","open_access":"1"}],"oa":1,"quality_controlled":"1","month":"09","related_material":{"record":[{"relation":"research_data","status":"public","id":"9741"}]},"author":[{"first_name":"Mato","last_name":"Lagator","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","full_name":"Lagator, Mato"},{"first_name":"Nick","last_name":"Colegrave","full_name":"Colegrave, Nick"},{"full_name":"Neve, Paul","last_name":"Neve","first_name":"Paul"}],"volume":281,"date_created":"2018-12-11T11:55:21Z","date_updated":"2023-02-23T14:06:44Z","year":"2014","acknowledgement":"The project was supported by Leverhulme Trust.","department":[{"_id":"CaGu"}],"publisher":"Royal Society, The","publication_status":"published","publist_id":"5019","article_number":"20141679","date_published":"2014-09-17T00:00:00Z","citation":{"ama":"Lagator M, Colegrave N, Neve P. Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses. Proceedings of the Royal Society of London Series B Biological Sciences. 2014;281(1794). doi:10.1098/rspb.2014.1679","ista":"Lagator M, Colegrave N, Neve P. 2014. Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses. Proceedings of the Royal Society of London Series B Biological Sciences. 281(1794), 20141679.","ieee":"M. Lagator, N. Colegrave, and P. Neve, “Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses,” Proceedings of the Royal Society of London Series B Biological Sciences, vol. 281, no. 1794. Royal Society, The, 2014.","apa":"Lagator, M., Colegrave, N., & Neve, P. (2014). Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses. Proceedings of the Royal Society of London Series B Biological Sciences. Royal Society, The. https://doi.org/10.1098/rspb.2014.1679","mla":"Lagator, Mato, et al. “Selection History and Epistatic Interactions Impact Dynamics of Adaptation to Novel Environmental Stresses.” Proceedings of the Royal Society of London Series B Biological Sciences, vol. 281, no. 1794, 20141679, Royal Society, The, 2014, doi:10.1098/rspb.2014.1679.","short":"M. Lagator, N. Colegrave, P. Neve, Proceedings of the Royal Society of London Series B Biological Sciences 281 (2014).","chicago":"Lagator, Mato, Nick Colegrave, and Paul Neve. “Selection History and Epistatic Interactions Impact Dynamics of Adaptation to Novel Environmental Stresses.” Proceedings of the Royal Society of London Series B Biological Sciences. Royal Society, The, 2014. https://doi.org/10.1098/rspb.2014.1679."},"publication":"Proceedings of the Royal Society of London Series B Biological Sciences","day":"17","scopus_import":1,"oa_version":"Submitted Version","user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","_id":"2036","intvolume":" 281","status":"public","title":"Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses","issue":"1794","abstract":[{"lang":"eng","text":" In rapidly changing environments, selection history may impact the dynamics of adaptation. Mutations selected in one environment may result in pleiotropic fitness trade-offs in subsequent novel environments, slowing the rates of adaptation. Epistatic interactions between mutations selected in sequential stressful environments may slow or accelerate subsequent rates of adaptation, depending on the nature of that interaction. We explored the dynamics of adaptation during sequential exposure to herbicides with different modes of action in Chlamydomonas reinhardtii. Evolution of resistance to two of the herbicides was largely independent of selection history. For carbetamide, previous adaptation to other herbicide modes of action positively impacted the likelihood of adaptation to this herbicide. Furthermore, while adaptation to all individual herbicides was associated with pleiotropic fitness costs in stress-free environments, we observed that accumulation of resistance mechanisms was accompanied by a reduction in overall fitness costs. We suggest that antagonistic epistasis may be a driving mechanism that enables populations to more readily adapt in novel environments. These findings highlight the potential for sequences of xenobiotics to facilitate the rapid evolution of multiple-drug and -pesticide resistance, as well as the potential for epistatic interactions between adaptive mutations to facilitate evolutionary rescue in rapidly changing environments. "}],"type":"journal_article"},{"type":"research_data_reference","abstract":[{"text":"In rapidly changing environments, selection history may impact the dynamics of adaptation. Mutations selected in one environment may result in pleiotropic fitness trade-offs in subsequent novel environments, slowing the rates of adaptation. Epistatic interactions between mutations selected in sequential stressful environments may slow or accelerate subsequent rates of adaptation, depending on the nature of that interaction. We explored the dynamics of adaptation during sequential exposure to herbicides with different modes of action in Chlamydomonas reinhardtii. Evolution of resistance to two of the herbicides was largely independent of selection history. For carbetamide, previous adaptation to other herbicide modes of action positively impacted the likelihood of adaptation to this herbicide. Furthermore, while adaptation to all individual herbicides was associated with pleiotropic fitness costs in stress-free environments, we observed that accumulation of resistance mechanisms was accompanied by a reduction in overall fitness costs. We suggest that antagonistic epistasis may be a driving mechanism that enables populations to more readily adapt in novel environments. These findings highlight the potential for sequences of xenobiotics to facilitate the rapid evolution of multiple-drug and -pesticide resistance, as well as the potential for epistatic interactions between adaptive mutations to facilitate evolutionary rescue in rapidly changing environments.","lang":"eng"}],"year":"2014","_id":"9741","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","publisher":"Dryad","department":[{"_id":"CaGu"}],"title":"Data from: Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses","status":"public","related_material":{"record":[{"status":"public","relation":"used_in_publication","id":"2036"}]},"author":[{"id":"345D25EC-F248-11E8-B48F-1D18A9856A87","first_name":"Mato","last_name":"Lagator","full_name":"Lagator, Mato"},{"last_name":"Colegrave","first_name":"Nick","full_name":"Colegrave, Nick"},{"last_name":"Neve","first_name":"Paul","full_name":"Neve, Paul"}],"oa_version":"Published Version","date_updated":"2023-02-23T10:25:31Z","date_created":"2021-07-28T08:48:06Z","article_processing_charge":"No","month":"08","day":"21","main_file_link":[{"open_access":"1","url":"https://doi.org/10.5061/dryad.85dn7"}],"oa":1,"citation":{"ama":"Lagator M, Colegrave N, Neve P. Data from: Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses. 2014. doi:10.5061/dryad.85dn7","ista":"Lagator M, Colegrave N, Neve P. 2014. Data from: Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses, Dryad, 10.5061/dryad.85dn7.","ieee":"M. Lagator, N. Colegrave, and P. Neve, “Data from: Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses.” Dryad, 2014.","apa":"Lagator, M., Colegrave, N., & Neve, P. (2014). Data from: Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses. Dryad. https://doi.org/10.5061/dryad.85dn7","mla":"Lagator, Mato, et al. Data from: Selection History and Epistatic Interactions Impact Dynamics of Adaptation to Novel Environmental Stresses. Dryad, 2014, doi:10.5061/dryad.85dn7.","short":"M. Lagator, N. Colegrave, P. Neve, (2014).","chicago":"Lagator, Mato, Nick Colegrave, and Paul Neve. “Data from: Selection History and Epistatic Interactions Impact Dynamics of Adaptation to Novel Environmental Stresses.” Dryad, 2014. https://doi.org/10.5061/dryad.85dn7."},"doi":"10.5061/dryad.85dn7","date_published":"2014-08-21T00:00:00Z"},{"publication_identifier":{"eissn":["1558-5646"],"issn":["0014-3820"]},"month":"06","external_id":{"pmid":["24495000"]},"quality_controlled":"1","doi":"10.1111/evo.12373","language":[{"iso":"eng"}],"pmid":1,"acknowledgement":"We thank the Functional Genomics Center Zurich for its service in generating sequencing data, M. Ackermann and E. Hayden for helpful discussions, A. de Visser for comments on earlier versions of this manuscript, and M. Moser for help with quantitative PCR. This work was supported by Swiss National Science Foundation (grant 315230–129708), as well as through the YeastX project of SystemsX.ch, and the University Priority Research Program in Systems Biology at the University of Zurich. RD acknowledges support from the Forschungskredit program of the University of Zurich. The authors declare no conflict of interest.","year":"2014","publisher":"Wiley","department":[{"_id":"CaGu"}],"publication_status":"published","related_material":{"record":[{"id":"9932","relation":"research_data","status":"public"}]},"author":[{"full_name":"Dhar, Riddhiman","last_name":"Dhar","first_name":"Riddhiman"},{"full_name":"Bergmiller, Tobias","last_name":"Bergmiller","first_name":"Tobias","orcid":"0000-0001-5396-4346","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Wagner, Andreas","last_name":"Wagner","first_name":"Andreas"}],"volume":68,"date_updated":"2023-02-23T14:13:27Z","date_created":"2021-08-17T09:03:09Z","scopus_import":"1","article_processing_charge":"No","day":"03","citation":{"apa":"Dhar, R., Bergmiller, T., & Wagner, A. (2014). Increased gene dosage plays a predominant role in the initial stages of evolution of duplicate TEM-1 beta lactamase genes. Evolution. Wiley. https://doi.org/10.1111/evo.12373","ieee":"R. Dhar, T. Bergmiller, and A. Wagner, “Increased gene dosage plays a predominant role in the initial stages of evolution of duplicate TEM-1 beta lactamase genes,” Evolution, vol. 68, no. 6. Wiley, pp. 1775–1791, 2014.","ista":"Dhar R, Bergmiller T, Wagner A. 2014. Increased gene dosage plays a predominant role in the initial stages of evolution of duplicate TEM-1 beta lactamase genes. Evolution. 68(6), 1775–1791.","ama":"Dhar R, Bergmiller T, Wagner A. Increased gene dosage plays a predominant role in the initial stages of evolution of duplicate TEM-1 beta lactamase genes. Evolution. 2014;68(6):1775-1791. doi:10.1111/evo.12373","chicago":"Dhar, Riddhiman, Tobias Bergmiller, and Andreas Wagner. “Increased Gene Dosage Plays a Predominant Role in the Initial Stages of Evolution of Duplicate TEM-1 Beta Lactamase Genes.” Evolution. Wiley, 2014. https://doi.org/10.1111/evo.12373.","short":"R. Dhar, T. Bergmiller, A. Wagner, Evolution 68 (2014) 1775–1791.","mla":"Dhar, Riddhiman, et al. “Increased Gene Dosage Plays a Predominant Role in the Initial Stages of Evolution of Duplicate TEM-1 Beta Lactamase Genes.” Evolution, vol. 68, no. 6, Wiley, 2014, pp. 1775–91, doi:10.1111/evo.12373."},"publication":"Evolution","page":"1775-1791","article_type":"original","date_published":"2014-06-03T00:00:00Z","type":"journal_article","issue":"6","abstract":[{"lang":"eng","text":"Gene duplication is important in evolution, because it provides new raw material for evolutionary adaptations. Several existing hypotheses about the causes of duplicate retention and diversification differ in their emphasis on gene dosage, subfunctionalization, and neofunctionalization. Little experimental data exist on the relative importance of gene expression changes and changes in coding regions for the evolution of duplicate genes. Furthermore, we do not know how strongly the environment could affect this importance. To address these questions, we performed evolution experiments with the TEM-1 beta lactamase gene in Escherichia coli to study the initial stages of duplicate gene evolution in the laboratory. We mimicked tandem duplication by inserting two copies of the TEM-1 gene on the same plasmid. We then subjected these copies to repeated cycles of mutagenesis and selection in various environments that contained antibiotics in different combinations and concentrations. Our experiments showed that gene dosage is the most important factor in the initial stages of duplicate gene evolution, and overshadows the importance of point mutations in the coding region."}],"user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","_id":"9931","intvolume":" 68","status":"public","title":"Increased gene dosage plays a predominant role in the initial stages of evolution of duplicate TEM-1 beta lactamase genes","oa_version":"None"},{"article_processing_charge":"No","day":"27","month":"01","oa":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.5061/dryad.jc402"}],"citation":{"mla":"Dhar, Riddhiman, et al. Data from: Increased Gene Dosage Plays a Predominant Role in the Initial Stages of Evolution of Duplicate TEM-1 Beta Lactamase Genes. Dryad, 2014, doi:10.5061/dryad.jc402.","short":"R. Dhar, T. Bergmiller, A. Wagner, (2014).","chicago":"Dhar, Riddhiman, Tobias Bergmiller, and Andreas Wagner. “Data from: Increased Gene Dosage Plays a Predominant Role in the Initial Stages of Evolution of Duplicate TEM-1 Beta Lactamase Genes.” Dryad, 2014. https://doi.org/10.5061/dryad.jc402.","ama":"Dhar R, Bergmiller T, Wagner A. Data from: Increased gene dosage plays a predominant role in the initial stages of evolution of duplicate TEM-1 beta lactamase genes. 2014. doi:10.5061/dryad.jc402","ista":"Dhar R, Bergmiller T, Wagner A. 2014. Data from: Increased gene dosage plays a predominant role in the initial stages of evolution of duplicate TEM-1 beta lactamase genes, Dryad, 10.5061/dryad.jc402.","ieee":"R. Dhar, T. Bergmiller, and A. Wagner, “Data from: Increased gene dosage plays a predominant role in the initial stages of evolution of duplicate TEM-1 beta lactamase genes.” Dryad, 2014.","apa":"Dhar, R., Bergmiller, T., & Wagner, A. (2014). Data from: Increased gene dosage plays a predominant role in the initial stages of evolution of duplicate TEM-1 beta lactamase genes. Dryad. https://doi.org/10.5061/dryad.jc402"},"date_published":"2014-01-27T00:00:00Z","doi":"10.5061/dryad.jc402","type":"research_data_reference","abstract":[{"text":"Gene duplication is important in evolution, because it provides new raw material for evolutionary adaptations. Several existing hypotheses about the causes of duplicate retention and diversification differ in their emphasis on gene dosage, sub-functionalization, and neo-functionalization. Little experimental data exists on the relative importance of gene expression changes and changes in coding regions for the evolution of duplicate genes. Furthermore, we do not know how strongly the environment could affect this importance. To address these questions, we performed evolution experiments with the TEM-1 beta lactamase gene in E. coli to study the initial stages of duplicate gene evolution in the laboratory. We mimicked tandem duplication by inserting two copies of the TEM-1 gene on the same plasmid. We then subjected these copies to repeated cycles of mutagenesis and selection in various environments that contained antibiotics in different combinations and concentrations. Our experiments showed that gene dosage is the most important factor in the initial stages of duplicate gene evolution, and overshadows the importance of point mutations in the coding region.","lang":"eng"}],"_id":"9932","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","year":"2014","publisher":"Dryad","department":[{"_id":"CaGu"}],"status":"public","title":"Data from: Increased gene dosage plays a predominant role in the initial stages of evolution of duplicate TEM-1 beta lactamase genes","related_material":{"record":[{"id":"9931","status":"public","relation":"used_in_publication"}]},"author":[{"first_name":"Riddhiman","last_name":"Dhar","full_name":"Dhar, Riddhiman"},{"last_name":"Bergmiller","first_name":"Tobias","orcid":"0000-0001-5396-4346","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","full_name":"Bergmiller, Tobias"},{"full_name":"Wagner, Andreas","last_name":"Wagner","first_name":"Andreas"}],"oa_version":"Published Version","date_updated":"2023-02-23T14:13:24Z","date_created":"2021-08-17T09:11:40Z"},{"article_processing_charge":"No","day":"07","scopus_import":"1","date_published":"2014-11-07T00:00:00Z","citation":{"mla":"Milenković, Ivan, et al. “Patterns of Hippocampal Tau Pathology Differentiate Neurodegenerative Dementias.” Dementia and Geriatric Cognitive Disorders, vol. 38, no. 5–6, Karger Publishers, 2014, pp. 375–88, doi:10.1159/000365548.","short":"I. Milenković, T. Petrov, G. Kovács, Dementia and Geriatric Cognitive Disorders 38 (2014) 375–388.","chicago":"Milenković, Ivan, Tatjana Petrov, and Gábor Kovács. “Patterns of Hippocampal Tau Pathology Differentiate Neurodegenerative Dementias.” Dementia and Geriatric Cognitive Disorders. Karger Publishers, 2014. https://doi.org/10.1159/000365548.","ama":"Milenković I, Petrov T, Kovács G. Patterns of hippocampal tau pathology differentiate neurodegenerative dementias. Dementia and Geriatric Cognitive Disorders. 2014;38(5-6):375-388. doi:10.1159/000365548","ista":"Milenković I, Petrov T, Kovács G. 2014. Patterns of hippocampal tau pathology differentiate neurodegenerative dementias. Dementia and Geriatric Cognitive Disorders. 38(5–6), 375–388.","apa":"Milenković, I., Petrov, T., & Kovács, G. (2014). Patterns of hippocampal tau pathology differentiate neurodegenerative dementias. Dementia and Geriatric Cognitive Disorders. Karger Publishers. https://doi.org/10.1159/000365548","ieee":"I. Milenković, T. Petrov, and G. Kovács, “Patterns of hippocampal tau pathology differentiate neurodegenerative dementias,” Dementia and Geriatric Cognitive Disorders, vol. 38, no. 5–6. Karger Publishers, pp. 375–388, 2014."},"publication":"Dementia and Geriatric Cognitive Disorders","page":"375 - 388","article_type":"original","issue":"5-6","abstract":[{"text":"Deposits of phosphorylated tau protein and convergence of pathology in the hippocampus are the hallmarks of neurodegenerative tauopathies. Thus we aimed to evaluate whether regional and cellular vulnerability patterns in the hippocampus distinguish tauopathies or are influenced by their concomitant presence. Methods: We created a heat map of phospho-tau (AT8) immunoreactivity patterns in 24 hippocampal subregions/layers in individuals with Alzheimer's disease (AD)-related neurofibrillary degeneration (n = 40), Pick's disease (n = 8), progressive supranuclear palsy (n = 7), corticobasal degeneration (n = 6), argyrophilic grain disease (AGD, n = 18), globular glial tauopathy (n = 5), and tau-astrogliopathy of the elderly (n = 10). AT8 immunoreactivity patterns were compared by mathematical analysis. Results: Our study reveals disease-specific hot spots and regional selective vulnerability for these disorders. The pattern of hippocampal AD-related tau pathology is strongly influenced by concomitant AGD. Mathematical analysis reveals that hippocampal involvement in primary tauopathies is distinguishable from early-stage AD-related neurofibrillary degeneration. Conclusion: Our data demonstrate disease-specific AT8 immunoreactivity patterns and hot spots in the hippocampus even in tauopathies, which primarily do not affect the hippocampus. These hot spots can be shifted to other regions by the co-occurrence of tauopathies like AGD. Our observations support the notion that globular glial tauopathies and tau-astrogliopathy of the elderly are distinct entities.","lang":"eng"}],"type":"journal_article","oa_version":"Published Version","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"1913","intvolume":" 38","status":"public","title":"Patterns of hippocampal tau pathology differentiate neurodegenerative dementias","publication_identifier":{"issn":["1420-8008"]},"month":"11","doi":"10.1159/000365548","language":[{"iso":"eng"}],"external_id":{"pmid":["25195847"]},"main_file_link":[{"open_access":"1","url":"https://kops.uni-konstanz.de/bitstream/123456789/42127/1/Milenkovic_2-17ivylo2up0798.pdf"}],"oa":1,"quality_controlled":"1","publist_id":"5181","author":[{"first_name":"Ivan","last_name":"Milenković","full_name":"Milenković, Ivan"},{"first_name":"Tatjana","last_name":"Petrov","id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9041-0905","full_name":"Petrov, Tatjana"},{"full_name":"Kovács, Gábor","first_name":"Gábor","last_name":"Kovács"}],"volume":38,"date_updated":"2023-10-17T10:21:17Z","date_created":"2018-12-11T11:54:41Z","pmid":1,"acknowledgement":"This study was supported by the European Commission’s 7th Framework Programme under GA No. 278486, ‘DEVELAGE’.","year":"2014","publisher":"Karger Publishers","department":[{"_id":"CaGu"}],"publication_status":"published"},{"language":[{"iso":"eng"}],"conference":{"start_date":"2013-07-06","location":"Amsterdam, Netherlands","end_date":"2013-07-10","name":"GECCO: Genetic and evolutionary computation conference"},"doi":"10.1145/2463372.2463568","quality_controlled":"1","project":[{"call_identifier":"FP7","name":"Limits to selection in biology and in evolutionary computation","_id":"25B07788-B435-11E9-9278-68D0E5697425","grant_number":"250152"}],"oa":1,"month":"07","date_updated":"2021-01-12T06:59:15Z","date_created":"2018-12-11T11:59:14Z","author":[{"full_name":"Barton, Nicholas H","last_name":"Barton","first_name":"Nicholas H","orcid":"0000-0002-8548-5240","id":"4880FE40-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Paixao, Tiago","orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","last_name":"Paixao","first_name":"Tiago"}],"publication_status":"published","department":[{"_id":"NiBa"},{"_id":"CaGu"}],"publisher":"ACM","year":"2013","file_date_updated":"2020-07-14T12:45:45Z","ec_funded":1,"publist_id":"4174","date_published":"2013-07-01T00:00:00Z","page":"1573 - 1580","publication":"Proceedings of the 15th annual conference on Genetic and evolutionary computation","citation":{"chicago":"Barton, Nicholas H, and Tiago Paixao. “Can Quantitative and Population Genetics Help Us Understand Evolutionary Computation?” In Proceedings of the 15th Annual Conference on Genetic and Evolutionary Computation, 1573–80. ACM, 2013. https://doi.org/10.1145/2463372.2463568.","mla":"Barton, Nicholas H., and Tiago Paixao. “Can Quantitative and Population Genetics Help Us Understand Evolutionary Computation?” Proceedings of the 15th Annual Conference on Genetic and Evolutionary Computation, ACM, 2013, pp. 1573–80, doi:10.1145/2463372.2463568.","short":"N.H. Barton, T. Paixao, in:, Proceedings of the 15th Annual Conference on Genetic and Evolutionary Computation, ACM, 2013, pp. 1573–1580.","ista":"Barton NH, Paixao T. 2013. Can quantitative and population genetics help us understand evolutionary computation? Proceedings of the 15th annual conference on Genetic and evolutionary computation. GECCO: Genetic and evolutionary computation conference, 1573–1580.","apa":"Barton, N. H., & Paixao, T. (2013). Can quantitative and population genetics help us understand evolutionary computation? In Proceedings of the 15th annual conference on Genetic and evolutionary computation (pp. 1573–1580). Amsterdam, Netherlands: ACM. https://doi.org/10.1145/2463372.2463568","ieee":"N. H. Barton and T. Paixao, “Can quantitative and population genetics help us understand evolutionary computation?,” in Proceedings of the 15th annual conference on Genetic and evolutionary computation, Amsterdam, Netherlands, 2013, pp. 1573–1580.","ama":"Barton NH, Paixao T. Can quantitative and population genetics help us understand evolutionary computation? In: Proceedings of the 15th Annual Conference on Genetic and Evolutionary Computation. ACM; 2013:1573-1580. doi:10.1145/2463372.2463568"},"day":"01","has_accepted_license":"1","scopus_import":1,"file":[{"creator":"system","content_type":"application/pdf","file_size":475844,"file_name":"IST-2016-564-v1+1_NickGECCO_2013_1_-1.pdf","access_level":"open_access","date_created":"2018-12-12T10:15:38Z","date_updated":"2020-07-14T12:45:45Z","checksum":"9d9be9090ce5c20766e0eb076ace5b98","file_id":"5159","relation":"main_file"}],"oa_version":"Submitted Version","pubrep_id":"564","title":"Can quantitative and population genetics help us understand evolutionary computation?","ddc":["570"],"status":"public","_id":"2718","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","abstract":[{"text":"Even though both population and quantitative genetics, and evolutionary computation, deal with the same questions, they have developed largely independently of each other. I review key results from each field, emphasising those that apply independently of the (usually unknown) relation between genotype and phenotype. The infinitesimal model provides a simple framework for predicting the response of complex traits to selection, which in biology has proved remarkably successful. This allows one to choose the schedule of population sizes and selection intensities that will maximise the response to selection, given that the total number of individuals realised, C = ∑t Nt, is constrained. This argument shows that for an additive trait (i.e., determined by the sum of effects of the genes), the optimum population size and the maximum possible response (i.e., the total change in trait mean) are both proportional to √C.","lang":"eng"}],"type":"conference"},{"quality_controlled":"1","project":[{"grant_number":"250152","_id":"25B07788-B435-11E9-9278-68D0E5697425","name":"Limits to selection in biology and in evolutionary computation","call_identifier":"FP7"}],"main_file_link":[{"open_access":"1","url":"http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3781978/"}],"external_id":{"pmid":["23934880"]},"oa":1,"language":[{"iso":"eng"}],"doi":"10.1534/genetics.113.153536","month":"10","publication_status":"published","department":[{"_id":"NiBa"},{"_id":"CaGu"}],"publisher":"Genetics Society of America","year":"2013","pmid":1,"date_created":"2018-12-11T11:59:15Z","date_updated":"2021-01-12T06:59:16Z","volume":195,"author":[{"full_name":"Long, Hongan","last_name":"Long","first_name":"Hongan"},{"full_name":"Paixao, Tiago","last_name":"Paixao","first_name":"Tiago","orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Azevedo, Ricardo","first_name":"Ricardo","last_name":"Azevedo"},{"full_name":"Zufall, Rebecca","last_name":"Zufall","first_name":"Rebecca"}],"ec_funded":1,"publist_id":"4172","page":"527-540","publication":"Genetics","citation":{"short":"H. Long, T. Paixao, R. Azevedo, R. Zufall, Genetics 195 (2013) 527–540.","mla":"Long, Hongan, et al. “Accumulation of Spontaneous Mutations in the Ciliate Tetrahymena Thermophila.” Genetics, vol. 195, no. 2, Genetics Society of America, 2013, pp. 527–40, doi:10.1534/genetics.113.153536.","chicago":"Long, Hongan, Tiago Paixao, Ricardo Azevedo, and Rebecca Zufall. “Accumulation of Spontaneous Mutations in the Ciliate Tetrahymena Thermophila.” Genetics. Genetics Society of America, 2013. https://doi.org/10.1534/genetics.113.153536.","ama":"Long H, Paixao T, Azevedo R, Zufall R. Accumulation of spontaneous mutations in the ciliate Tetrahymena thermophila. Genetics. 2013;195(2):527-540. doi:10.1534/genetics.113.153536","apa":"Long, H., Paixao, T., Azevedo, R., & Zufall, R. (2013). Accumulation of spontaneous mutations in the ciliate Tetrahymena thermophila. Genetics. Genetics Society of America. https://doi.org/10.1534/genetics.113.153536","ieee":"H. Long, T. Paixao, R. Azevedo, and R. Zufall, “Accumulation of spontaneous mutations in the ciliate Tetrahymena thermophila,” Genetics, vol. 195, no. 2. Genetics Society of America, pp. 527–540, 2013.","ista":"Long H, Paixao T, Azevedo R, Zufall R. 2013. Accumulation of spontaneous mutations in the ciliate Tetrahymena thermophila. Genetics. 195(2), 527–540."},"date_published":"2013-10-01T00:00:00Z","scopus_import":1,"day":"01","article_processing_charge":"No","status":"public","title":"Accumulation of spontaneous mutations in the ciliate Tetrahymena thermophila","intvolume":" 195","_id":"2720","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","oa_version":"Submitted Version","type":"journal_article","abstract":[{"text":"Knowledge of the rate and fitness effects of mutations is essential for understanding the process of evolution. Mutations are inherently difficult to study because they are rare and are frequently eliminated by natural selection. In the ciliate Tetrahymena thermophila, mutations can accumulate in the germline genome without being exposed to selection. We have conducted a mutation accumulation (MA) experiment in this species. Assuming that all mutations are deleterious and have the same effect, we estimate that the deleterious mutation rate per haploid germline genome per generation is U = 0.0047 (95% credible interval: 0.0015, 0.0125), and that germline mutations decrease fitness by s = 11% when expressed in a homozygous state (95% CI: 4.4%, 27%). We also estimate that deleterious mutations are partially recessive on average (h = 0.26; 95% CI: –0.022, 0.62) and that the rate of lethal mutations is <10% of the deleterious mutation rate. Comparisons between the observed evolutionary responses in the germline and somatic genomes and the results from individual-based simulations of MA suggest that the two genomes have similar mutational parameters. These are the first estimates of the deleterious mutation rate and fitness effects from the eukaryotic supergroup Chromalveolata and are within the range of those of other eukaryotes.","lang":"eng"}],"issue":"2"},{"abstract":[{"lang":"eng","text":"Prediction of the evolutionary process is a long standing problem both in the theory of evolutionary biology and evolutionary computation (EC). It has long been realized that heritable variation is crucial to both the response to selection and the success of genetic algorithms. However, not all variation contributes in the same way to the response. Quantitative genetics has developed a large body of work trying to estimate and understand how different components of the variance in fitness in the population contribute to the response to selection. We illustrate how to apply some concepts of quantitative genetics to the analysis of genetic algorithms. In particular, we derive estimates for the short term prediction of the response to selection and we use variance decomposition to gain insight on local aspects of the landscape. Finally, we propose a new population based genetic algorithm that uses these methods to improve its operation."}],"publist_id":"4173","ec_funded":1,"type":"conference","date_created":"2018-12-11T11:59:15Z","date_updated":"2021-01-12T06:59:15Z","oa_version":"None","author":[{"full_name":"Paixao, Tiago","orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","last_name":"Paixao","first_name":"Tiago"},{"id":"4880FE40-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8548-5240","first_name":"Nicholas H","last_name":"Barton","full_name":"Barton, Nicholas H"}],"title":"A variance decomposition approach to the analysis of genetic algorithms","status":"public","publication_status":"published","department":[{"_id":"NiBa"},{"_id":"CaGu"}],"publisher":"ACM","_id":"2719","year":"2013","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"07","day":"01","scopus_import":1,"language":[{"iso":"eng"}],"conference":{"location":"Amsterdam, Netherlands","start_date":"2013-07-06","end_date":"2013-07-10","name":"GECCO: Genetic and evolutionary computation conference"},"date_published":"2013-07-01T00:00:00Z","doi":"10.1145/2463372.2463470","quality_controlled":"1","page":"845 - 852","project":[{"call_identifier":"FP7","name":"Limits to selection in biology and in evolutionary computation","grant_number":"250152","_id":"25B07788-B435-11E9-9278-68D0E5697425"}],"publication":"Proceedings of the 15th annual conference on Genetic and evolutionary computation","citation":{"ieee":"T. Paixao and N. H. Barton, “A variance decomposition approach to the analysis of genetic algorithms,” in Proceedings of the 15th annual conference on Genetic and evolutionary computation, Amsterdam, Netherlands, 2013, pp. 845–852.","apa":"Paixao, T., & Barton, N. H. (2013). A variance decomposition approach to the analysis of genetic algorithms. In Proceedings of the 15th annual conference on Genetic and evolutionary computation (pp. 845–852). Amsterdam, Netherlands: ACM. https://doi.org/10.1145/2463372.2463470","ista":"Paixao T, Barton NH. 2013. A variance decomposition approach to the analysis of genetic algorithms. Proceedings of the 15th annual conference on Genetic and evolutionary computation. GECCO: Genetic and evolutionary computation conference, 845–852.","ama":"Paixao T, Barton NH. A variance decomposition approach to the analysis of genetic algorithms. In: Proceedings of the 15th Annual Conference on Genetic and Evolutionary Computation. ACM; 2013:845-852. doi:10.1145/2463372.2463470","chicago":"Paixao, Tiago, and Nicholas H Barton. “A Variance Decomposition Approach to the Analysis of Genetic Algorithms.” In Proceedings of the 15th Annual Conference on Genetic and Evolutionary Computation, 845–52. ACM, 2013. https://doi.org/10.1145/2463372.2463470.","short":"T. Paixao, N.H. Barton, in:, Proceedings of the 15th Annual Conference on Genetic and Evolutionary Computation, ACM, 2013, pp. 845–852.","mla":"Paixao, Tiago, and Nicholas H. Barton. “A Variance Decomposition Approach to the Analysis of Genetic Algorithms.” Proceedings of the 15th Annual Conference on Genetic and Evolutionary Computation, ACM, 2013, pp. 845–52, doi:10.1145/2463372.2463470."}},{"language":[{"iso":"eng"}],"doi":"10.1126/science.1229858","date_published":"2013-01-04T00:00:00Z","page":"91 - 95","quality_controlled":"1","citation":{"short":"Y. Wakamoto, N. Dhar, R.P. Chait, K. Schneider, F. Signorino Gelo, S. Leibler, J. Mckinney, Science 339 (2013) 91–95.","mla":"Wakamoto, Yurichi, et al. “Dynamic Persistence of Antibiotic-Stressed Mycobacteria.” Science, vol. 339, no. 6115, American Association for the Advancement of Science, 2013, pp. 91–95, doi:10.1126/science.1229858.","chicago":"Wakamoto, Yurichi, Neraaj Dhar, Remy P Chait, Katrin Schneider, François Signorino Gelo, Stanislas Leibler, and John Mckinney. “Dynamic Persistence of Antibiotic-Stressed Mycobacteria.” Science. American Association for the Advancement of Science, 2013. https://doi.org/10.1126/science.1229858.","ama":"Wakamoto Y, Dhar N, Chait RP, et al. Dynamic persistence of antibiotic-stressed mycobacteria. Science. 2013;339(6115):91-95. doi:10.1126/science.1229858","ieee":"Y. Wakamoto et al., “Dynamic persistence of antibiotic-stressed mycobacteria,” Science, vol. 339, no. 6115. American Association for the Advancement of Science, pp. 91–95, 2013.","apa":"Wakamoto, Y., Dhar, N., Chait, R. P., Schneider, K., Signorino Gelo, F., Leibler, S., & Mckinney, J. (2013). Dynamic persistence of antibiotic-stressed mycobacteria. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.1229858","ista":"Wakamoto Y, Dhar N, Chait RP, Schneider K, Signorino Gelo F, Leibler S, Mckinney J. 2013. Dynamic persistence of antibiotic-stressed mycobacteria. Science. 339(6115), 91–95."},"publication":"Science","day":"04","month":"01","scopus_import":1,"volume":339,"oa_version":"None","date_created":"2018-12-11T11:46:48Z","date_updated":"2021-01-12T08:01:06Z","author":[{"first_name":"Yurichi","last_name":"Wakamoto","full_name":"Wakamoto, Yurichi"},{"full_name":"Dhar, Neraaj","last_name":"Dhar","first_name":"Neraaj"},{"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":"Schneider, Katrin","first_name":"Katrin","last_name":"Schneider"},{"last_name":"Signorino Gelo","first_name":"François","full_name":"Signorino Gelo, François"},{"first_name":"Stanislas","last_name":"Leibler","full_name":"Leibler, Stanislas"},{"first_name":"John","last_name":"Mckinney","full_name":"Mckinney, John"}],"publisher":"American Association for the Advancement of Science","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"intvolume":" 339","publication_status":"published","title":"Dynamic persistence of antibiotic-stressed mycobacteria","status":"public","_id":"499","year":"2013","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publist_id":"7321","issue":"6115","abstract":[{"text":"Exposure of an isogenic bacterial population to a cidal antibiotic typically fails to eliminate a small fraction of refractory cells. Historically, fractional killing has been attributed to infrequently dividing or nondividing "persisters." Using microfluidic cultures and time-lapse microscopy, we found that Mycobacterium smegmatis persists by dividing in the presence of the drug isoniazid (INH). Although persistence in these studies was characterized by stable numbers of cells, this apparent stability was actually a dynamic state of balanced division and death. Single cells expressed catalase-peroxidase (KatG), which activates INH, in stochastic pulses that were negatively correlated with cell survival. These behaviors may reflect epigenetic effects, because KatG pulsing and death were correlated between sibling cells. Selection of lineages characterized by infrequent KatG pulsing could allow nonresponsive adaptation during prolonged drug exposure.","lang":"eng"}],"type":"journal_article"},{"month":"05","publication_identifier":{"eissn":["1471-2954"]},"quality_controlled":"1","oa":1,"external_id":{"pmid":["23516238"]},"main_file_link":[{"url":"http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3619501/","open_access":"1"}],"language":[{"iso":"eng"}],"doi":"10.1098/rspb.2012.3035","publist_id":"3939","publication_status":"published","publisher":"The Royal Society","department":[{"_id":"CaGu"}],"year":"2013","pmid":1,"date_updated":"2023-10-18T06:43:23Z","date_created":"2018-12-11T11:59:56Z","volume":280,"author":[{"first_name":"Dominik","last_name":"Refardt","full_name":"Refardt, Dominik"},{"first_name":"Tobias","last_name":"Bergmiller","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5396-4346","full_name":"Bergmiller, Tobias"},{"full_name":"Kümmerli, Rolf","last_name":"Kümmerli","first_name":"Rolf"}],"related_material":{"record":[{"relation":"research_data","status":"public","id":"9751"}]},"scopus_import":"1","day":"22","article_processing_charge":"No","article_type":"original","publication":"Proceedings of the Royal Society of London Series B Biological Sciences","citation":{"ista":"Refardt D, Bergmiller T, Kümmerli R. 2013. Altruism can evolve when relatedness is low: Evidence from bacteria committing suicide upon phage infection. Proceedings of the Royal Society of London Series B Biological Sciences. 280(1759).","apa":"Refardt, D., Bergmiller, T., & Kümmerli, R. (2013). Altruism can evolve when relatedness is low: Evidence from bacteria committing suicide upon phage infection. Proceedings of the Royal Society of London Series B Biological Sciences. The Royal Society. https://doi.org/10.1098/rspb.2012.3035","ieee":"D. Refardt, T. Bergmiller, and R. Kümmerli, “Altruism can evolve when relatedness is low: Evidence from bacteria committing suicide upon phage infection,” Proceedings of the Royal Society of London Series B Biological Sciences, vol. 280, no. 1759. The Royal Society, 2013.","ama":"Refardt D, Bergmiller T, Kümmerli R. Altruism can evolve when relatedness is low: Evidence from bacteria committing suicide upon phage infection. Proceedings of the Royal Society of London Series B Biological Sciences. 2013;280(1759). doi:10.1098/rspb.2012.3035","chicago":"Refardt, Dominik, Tobias Bergmiller, and Rolf Kümmerli. “Altruism Can Evolve When Relatedness Is Low: Evidence from Bacteria Committing Suicide upon Phage Infection.” Proceedings of the Royal Society of London Series B Biological Sciences. The Royal Society, 2013. https://doi.org/10.1098/rspb.2012.3035.","mla":"Refardt, Dominik, et al. “Altruism Can Evolve When Relatedness Is Low: Evidence from Bacteria Committing Suicide upon Phage Infection.” Proceedings of the Royal Society of London Series B Biological Sciences, vol. 280, no. 1759, The Royal Society, 2013, doi:10.1098/rspb.2012.3035.","short":"D. Refardt, T. Bergmiller, R. Kümmerli, Proceedings of the Royal Society of London Series B Biological Sciences 280 (2013)."},"date_published":"2013-05-22T00:00:00Z","type":"journal_article","abstract":[{"lang":"eng","text":"High relatedness among interacting individuals has generally been considered a precondition for the evolution of altruism. However, kin-selection theory also predicts the evolution of altruism when relatedness is low, as long as the cost of the altruistic act is minor compared with its benefit. Here, we demonstrate evidence for a low-cost altruistic act in bacteria. We investigated Escherichia coli responding to the attack of an obligately lytic phage by committing suicide in order to prevent parasite transmission to nearby relatives. We found that bacterial suicide provides large benefits to survivors at marginal costs to committers. The cost of suicide was low, because infected cells are moribund, rapidly dying upon phage infection, such that no more opportunity for reproduction remains. As a consequence of its marginal cost, host suicide was selectively favoured even when relatedness between committers and survivors approached zero. Altogether, our findings demonstrate that low-cost suicide can evolve with ease, represents an effective host-defence strategy, and seems to be widespread among microbes. Moreover, low-cost suicide might also occur in higher organisms as exemplified by infected social insect workers leaving the colony to die in isolation."}],"issue":"1759","status":"public","title":"Altruism can evolve when relatedness is low: Evidence from bacteria committing suicide upon phage infection","intvolume":" 280","_id":"2853","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Submitted Version"},{"abstract":[{"lang":"eng","text":"High relatedness among interacting individuals has generally been considered a precondition for the evolution of altruism. However, kin-selection theory also predicts the evolution of altruism when relatedness is low, as long as the cost of the altruistic act is minor compared to its benefit. Here, we demonstrate evidence for a low-cost altruistic act in bacteria. We investigated Escherichia coli responding to the attack of an obligately lytic phage by committing suicide in order to prevent parasite transmission to nearby relatives. We found that bacterial suicide provides large benefits to survivors at marginal costs to committers. The cost of suicide was low because infected cells are moribund, rapidly dying upon phage infection, such that no more opportunity for reproduction remains. As a consequence of its marginal cost, host suicide was selectively favoured even when relatedness between committers and survivors approached zero. Altogether, our findings demonstrate that low-cost suicide can evolve with ease, represents an effective host-defence strategy, and seems to be widespread among microbes. Moreover, low-cost suicide might also occur in higher organisms as exemplified by infected social insect workers leaving the colony to die in isolation."}],"type":"research_data_reference","author":[{"full_name":"Refardt, Dominik","last_name":"Refardt","first_name":"Dominik"},{"first_name":"Tobias","last_name":"Bergmiller","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5396-4346","full_name":"Bergmiller, Tobias"},{"first_name":"Rolf","last_name":"Kümmerli","full_name":"Kümmerli, Rolf"}],"related_material":{"record":[{"id":"2853","status":"public","relation":"used_in_publication"}]},"date_created":"2021-07-30T08:08:09Z","date_updated":"2023-10-18T06:43:22Z","oa_version":"Published Version","year":"2013","_id":"9751","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","status":"public","title":"Data from: Altruism can evolve when relatedness is low: evidence from bacteria committing suicide upon phage infection","department":[{"_id":"CaGu"}],"publisher":"Dryad","day":"21","month":"03","article_processing_charge":"No","date_published":"2013-03-21T00:00:00Z","doi":"10.5061/dryad.b1q2n","citation":{"mla":"Refardt, Dominik, et al. Data from: Altruism Can Evolve When Relatedness Is Low: Evidence from Bacteria Committing Suicide upon Phage Infection. Dryad, 2013, doi:10.5061/dryad.b1q2n.","short":"D. Refardt, T. Bergmiller, R. Kümmerli, (2013).","chicago":"Refardt, Dominik, Tobias Bergmiller, and Rolf Kümmerli. “Data from: Altruism Can Evolve When Relatedness Is Low: Evidence from Bacteria Committing Suicide upon Phage Infection.” Dryad, 2013. https://doi.org/10.5061/dryad.b1q2n.","ama":"Refardt D, Bergmiller T, Kümmerli R. Data from: Altruism can evolve when relatedness is low: evidence from bacteria committing suicide upon phage infection. 2013. doi:10.5061/dryad.b1q2n","ista":"Refardt D, Bergmiller T, Kümmerli R. 2013. Data from: Altruism can evolve when relatedness is low: evidence from bacteria committing suicide upon phage infection, Dryad, 10.5061/dryad.b1q2n.","apa":"Refardt, D., Bergmiller, T., & Kümmerli, R. (2013). Data from: Altruism can evolve when relatedness is low: evidence from bacteria committing suicide upon phage infection. Dryad. https://doi.org/10.5061/dryad.b1q2n","ieee":"D. Refardt, T. Bergmiller, and R. Kümmerli, “Data from: Altruism can evolve when relatedness is low: evidence from bacteria committing suicide upon phage infection.” Dryad, 2013."},"oa":1,"main_file_link":[{"url":"https://doi.org/10.5061/dryad.b1q2n","open_access":"1"}]},{"citation":{"chicago":"Henzinger, Thomas A, and Maria Mateescu. “The Propagation Approach for Computing Biochemical Reaction Networks.” IEEE ACM Transactions on Computational Biology and Bioinformatics. IEEE, 2012. https://doi.org/10.1109/TCBB.2012.91.","mla":"Henzinger, Thomas A., and Maria Mateescu. “The Propagation Approach for Computing Biochemical Reaction Networks.” IEEE ACM Transactions on Computational Biology and Bioinformatics, vol. 10, no. 2, IEEE, 2012, pp. 310–22, doi:10.1109/TCBB.2012.91.","short":"T.A. Henzinger, M. Mateescu, IEEE ACM Transactions on Computational Biology and Bioinformatics 10 (2012) 310–322.","ista":"Henzinger TA, Mateescu M. 2012. The propagation approach for computing biochemical reaction networks. IEEE ACM Transactions on Computational Biology and Bioinformatics. 10(2), 310–322.","ieee":"T. A. Henzinger and M. Mateescu, “The propagation approach for computing biochemical reaction networks,” IEEE ACM Transactions on Computational Biology and Bioinformatics, vol. 10, no. 2. IEEE, pp. 310–322, 2012.","apa":"Henzinger, T. A., & Mateescu, M. (2012). The propagation approach for computing biochemical reaction networks. IEEE ACM Transactions on Computational Biology and Bioinformatics. IEEE. https://doi.org/10.1109/TCBB.2012.91","ama":"Henzinger TA, Mateescu M. The propagation approach for computing biochemical reaction networks. IEEE ACM Transactions on Computational Biology and Bioinformatics. 2012;10(2):310-322. doi:10.1109/TCBB.2012.91"},"publication":"IEEE ACM Transactions on Computational Biology and Bioinformatics","page":"310 - 322","date_published":"2012-07-03T00:00:00Z","scopus_import":1,"day":"03","_id":"2302","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":" 10","status":"public","title":"The propagation approach for computing biochemical reaction networks","oa_version":"None","type":"journal_article","issue":"2","abstract":[{"text":"We introduce propagation models (PMs), a formalism able to express several kinds of equations that describe the behavior of biochemical reaction networks. Furthermore, we introduce the propagation abstract data type (PADT), which separates concerns regarding different numerical algorithms for the transient analysis of biochemical reaction networks from concerns regarding their implementation, thus allowing for portable and efficient solutions. The state of a propagation abstract data type is given by a vector that assigns mass values to a set of nodes, and its (next) operator propagates mass values through this set of nodes. We propose an approximate implementation of the (next) operator, based on threshold abstraction, which propagates only "significant" mass values and thus achieves a compromise between efficiency and accuracy. Finally, we give three use cases for propagation models: the chemical master equation (CME), the reaction rate equation (RRE), and a hybrid method that combines these two equations. These three applications use propagation models in order to propagate probabilities and/or expected values and variances of the model's variables.","lang":"eng"}],"external_id":{"pmid":["22778152"]},"project":[{"_id":"25EE3708-B435-11E9-9278-68D0E5697425","grant_number":"267989","name":"Quantitative Reactive Modeling","call_identifier":"FP7"}],"quality_controlled":"1","doi":"10.1109/TCBB.2012.91","language":[{"iso":"eng"}],"month":"07","pmid":1,"year":"2012","publisher":"IEEE","department":[{"_id":"ToHe"},{"_id":"CaGu"}],"publication_status":"published","author":[{"full_name":"Henzinger, Thomas A","id":"40876CD8-F248-11E8-B48F-1D18A9856A87","orcid":"0000−0002−2985−7724","first_name":"Thomas A","last_name":"Henzinger"},{"full_name":"Mateescu, Maria","last_name":"Mateescu","first_name":"Maria","id":"3B43276C-F248-11E8-B48F-1D18A9856A87"}],"volume":10,"date_created":"2018-12-11T11:56:52Z","date_updated":"2021-01-12T06:56:38Z","publist_id":"4625","ec_funded":1},{"publist_id":"3790","date_created":"2018-12-11T12:00:28Z","date_updated":"2021-01-12T07:39:56Z","volume":86,"author":[{"full_name":"Hadizadeh Yazdi, Nastaran","last_name":"Hadizadeh Yazdi","first_name":"Nastaran"},{"orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C","full_name":"Guet, Calin C"},{"last_name":"Johnson","first_name":"Reid","full_name":"Johnson, Reid"},{"last_name":"Marko","first_name":"John","full_name":"Marko, John"}],"publication_status":"published","publisher":"Wiley-Blackwell","department":[{"_id":"CaGu"}],"acknowledgement":"We thank Professor Philippe Cluzel and Mr Lance Min for providing advice and materials. Jeannette Chau provided technical support. Work at NU was supported by NSF Grants DMR-0715099, MCB-1022117, DMR-1206868, DMR-0520513 and DMR-1121262 (NU-MRSEC), by NIH-NCI Grant U54CA143869-01 (NU-PS-OC) and by the Chicago Biomedical Consortium with support from the Searle Funds at the Chicago Community Trust. Work at UCLA was supported by NIH Grant GM038509.","year":"2012","month":"11","language":[{"iso":"eng"}],"doi":"10.1111/mmi.12071","quality_controlled":"1","main_file_link":[{"open_access":"1","url":"http://europepmc.org/articles/pmc3524407"}],"oa":1,"abstract":[{"lang":"eng","text":"We examine whether the Escherichia coli chromosome is folded into a self-adherent nucleoprotein complex, or alternately is a confined but otherwise unconstrained self-avoiding polymer. We address this through in vivo visualization, using an inducible GFP fusion to the nucleoid-associated protein Fis to non-specifically decorate the entire chromosome. For a range of different growth conditions, the chromosome is a compact structure that does not fill the volume of the cell, and which moves from the new pole to the cell centre. During rapid growth, chromosome segregation occurs well before cell division, with daughter chromosomes coupled by a thin inter-daughter filament before complete segregation, whereas during slow growth chromosomes stay adjacent until cell division occurs. Image correlation analysis indicates that sub-nucleoid structure is stable on a 1min timescale, comparable to the timescale for redistribution time measured for GFP-Fis after photobleaching. Optical deconvolution and writhe calculation analysis indicate that the nucleoid has a large-scale coiled organization rather than being an amorphous mass. Our observations are consistent with the chromosome having a self-adherent filament organization."}],"issue":"6","type":"journal_article","oa_version":"Submitted Version","title":"Variation of the folding and dynamics of the Escherichia coli chromosome with growth conditions","status":"public","intvolume":" 86","_id":"2943","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","day":"09","scopus_import":1,"date_published":"2012-11-09T00:00:00Z","page":"1318 - 1333","publication":"Molecular Microbiology","citation":{"ama":"Hadizadeh Yazdi N, Guet CC, Johnson R, Marko J. Variation of the folding and dynamics of the Escherichia coli chromosome with growth conditions. Molecular Microbiology. 2012;86(6):1318-1333. doi:10.1111/mmi.12071","ista":"Hadizadeh Yazdi N, Guet CC, Johnson R, Marko J. 2012. Variation of the folding and dynamics of the Escherichia coli chromosome with growth conditions. Molecular Microbiology. 86(6), 1318–1333.","apa":"Hadizadeh Yazdi, N., Guet, C. C., Johnson, R., & Marko, J. (2012). Variation of the folding and dynamics of the Escherichia coli chromosome with growth conditions. Molecular Microbiology. Wiley-Blackwell. https://doi.org/10.1111/mmi.12071","ieee":"N. Hadizadeh Yazdi, C. C. Guet, R. Johnson, and J. Marko, “Variation of the folding and dynamics of the Escherichia coli chromosome with growth conditions,” Molecular Microbiology, vol. 86, no. 6. Wiley-Blackwell, pp. 1318–1333, 2012.","mla":"Hadizadeh Yazdi, Nastaran, et al. “Variation of the Folding and Dynamics of the Escherichia Coli Chromosome with Growth Conditions.” Molecular Microbiology, vol. 86, no. 6, Wiley-Blackwell, 2012, pp. 1318–33, doi:10.1111/mmi.12071.","short":"N. Hadizadeh Yazdi, C.C. Guet, R. Johnson, J. Marko, Molecular Microbiology 86 (2012) 1318–1333.","chicago":"Hadizadeh Yazdi, Nastaran, Calin C Guet, Reid Johnson, and John Marko. “Variation of the Folding and Dynamics of the Escherichia Coli Chromosome with Growth Conditions.” Molecular Microbiology. Wiley-Blackwell, 2012. https://doi.org/10.1111/mmi.12071."}},{"date_published":"2012-06-28T00:00:00Z","publication":"PLoS Genetics","citation":{"ista":"Bergmiller T, Ackermann M, Silander O. 2012. Patterns of evolutionary conservation of essential genes correlate with their compensability. PLoS Genetics. 8(6), e1002803.","apa":"Bergmiller, T., Ackermann, M., & Silander, O. (2012). Patterns of evolutionary conservation of essential genes correlate with their compensability. PLoS Genetics. Public Library of Science. https://doi.org/10.1371/journal.pgen.1002803","ieee":"T. Bergmiller, M. Ackermann, and O. Silander, “Patterns of evolutionary conservation of essential genes correlate with their compensability,” PLoS Genetics, vol. 8, no. 6. Public Library of Science, 2012.","ama":"Bergmiller T, Ackermann M, Silander O. Patterns of evolutionary conservation of essential genes correlate with their compensability. PLoS Genetics. 2012;8(6). doi:10.1371/journal.pgen.1002803","chicago":"Bergmiller, Tobias, Martin Ackermann, and Olin Silander. “Patterns of Evolutionary Conservation of Essential Genes Correlate with Their Compensability.” PLoS Genetics. Public Library of Science, 2012. https://doi.org/10.1371/journal.pgen.1002803.","mla":"Bergmiller, Tobias, et al. “Patterns of Evolutionary Conservation of Essential Genes Correlate with Their Compensability.” PLoS Genetics, vol. 8, no. 6, e1002803, Public Library of Science, 2012, doi:10.1371/journal.pgen.1002803.","short":"T. Bergmiller, M. Ackermann, O. Silander, PLoS Genetics 8 (2012)."},"day":"28","has_accepted_license":"1","scopus_import":1,"pubrep_id":"386","file":[{"creator":"system","file_size":2674138,"content_type":"application/pdf","file_name":"IST-2015-386-v1+1_journal.pgen.1002803.pdf","access_level":"open_access","date_created":"2018-12-12T10:12:52Z","date_updated":"2020-07-14T12:46:01Z","checksum":"f8506fb579eda6fc5613ba9bf421b86a","file_id":"4973","relation":"main_file"}],"oa_version":"Published Version","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","_id":"3130","status":"public","ddc":["576"],"title":"Patterns of evolutionary conservation of essential genes correlate with their compensability","intvolume":" 8","abstract":[{"lang":"eng","text":"Essential genes code for fundamental cellular functions required for the viability of an organism. For this reason, essential genes are often highly conserved across organisms. However, this is not always the case: orthologues of genes that are essential in one organism are sometimes not essential in other organisms or are absent from their genomes. This suggests that, in the course of evolution, essential genes can be rendered nonessential. How can a gene become non-essential? Here we used genetic manipulation to deplete the products of 26 different essential genes in Escherichia coli. This depletion results in a lethal phenotype, which could often be rescued by the overexpression of a non-homologous, non-essential gene, most likely through replacement of the essential function. We also show that, in a smaller number of cases, the essential genes can be fully deleted from the genome, suggesting that complete functional replacement is possible. Finally, we show that essential genes whose function can be replaced in the laboratory are more likely to be non-essential or not present in other taxa. These results are consistent with the notion that patterns of evolutionary conservation of essential genes are influenced by their compensability-that is, by how easily they can be functionally replaced, for example through increased expression of other genes."}],"issue":"6","type":"journal_article","doi":"10.1371/journal.pgen.1002803","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":"06","author":[{"full_name":"Bergmiller, Tobias","last_name":"Bergmiller","first_name":"Tobias","orcid":"0000-0001-5396-4346","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Martin","last_name":"Ackermann","full_name":"Ackermann, Martin"},{"first_name":"Olin","last_name":"Silander","full_name":"Silander, Olin"}],"date_created":"2018-12-11T12:01:34Z","date_updated":"2021-01-12T07:41:16Z","volume":8,"acknowledgement":"We thank Alex Boehm for discussions and comments.","year":"2012","publication_status":"published","department":[{"_id":"CaGu"}],"publisher":"Public Library of Science","file_date_updated":"2020-07-14T12:46:01Z","publist_id":"3567","article_number":"e1002803"},{"year":"2012","_id":"3136","acknowledgement":"This work was supported by the ERC Advanced Investigator grant on Quantitative Reactive Modeling (QUAREM) and by the Swiss National Science Foundation.","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","publisher":"Springer","department":[{"_id":"CaGu"},{"_id":"ToHe"}],"title":"Delayed continuous time Markov chains for genetic regulatory circuits","status":"public","publication_status":"published","author":[{"full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet"},{"id":"335E5684-F248-11E8-B48F-1D18A9856A87","last_name":"Gupta","first_name":"Ashutosh","full_name":"Gupta, Ashutosh"},{"full_name":"Henzinger, Thomas A","orcid":"0000−0002−2985−7724","id":"40876CD8-F248-11E8-B48F-1D18A9856A87","last_name":"Henzinger","first_name":"Thomas A"},{"first_name":"Maria","last_name":"Mateescu","id":"3B43276C-F248-11E8-B48F-1D18A9856A87","full_name":"Mateescu, Maria"},{"full_name":"Sezgin, Ali","first_name":"Ali","last_name":"Sezgin","id":"4C7638DA-F248-11E8-B48F-1D18A9856A87"}],"oa_version":"None","volume":"7358 ","date_updated":"2021-01-12T07:41:18Z","date_created":"2018-12-11T12:01:36Z","type":"conference","alternative_title":["LNCS"],"publist_id":"3561","ec_funded":1,"abstract":[{"lang":"eng","text":"Continuous-time Markov chains (CTMC) with their rich theory and efficient simulation algorithms have been successfully used in modeling stochastic processes in diverse areas such as computer science, physics, and biology. However, systems that comprise non-instantaneous events cannot be accurately and efficiently modeled with CTMCs. In this paper we define delayed CTMCs, an extension of CTMCs that allows for the specification of a lower bound on the time interval between an event's initiation and its completion, and we propose an algorithm for the computation of their behavior. Our algorithm effectively decomposes the computation into two stages: a pure CTMC governs event initiations while a deterministic process guarantees lower bounds on event completion times. Furthermore, from the nature of delayed CTMCs, we obtain a parallelized version of our algorithm. We use our formalism to model genetic regulatory circuits (biological systems where delayed events are common) and report on the results of our numerical algorithm as run on a cluster. We compare performance and accuracy of our results with results obtained by using pure CTMCs. © 2012 Springer-Verlag."}],"citation":{"ama":"Guet CC, Gupta A, Henzinger TA, Mateescu M, Sezgin A. Delayed continuous time Markov chains for genetic regulatory circuits. In: Vol 7358. Springer; 2012:294-309. doi:10.1007/978-3-642-31424-7_24","ieee":"C. C. Guet, A. Gupta, T. A. Henzinger, M. Mateescu, and A. Sezgin, “Delayed continuous time Markov chains for genetic regulatory circuits,” presented at the CAV: Computer Aided Verification, Berkeley, CA, USA, 2012, vol. 7358, pp. 294–309.","apa":"Guet, C. C., Gupta, A., Henzinger, T. A., Mateescu, M., & Sezgin, A. (2012). Delayed continuous time Markov chains for genetic regulatory circuits (Vol. 7358, pp. 294–309). Presented at the CAV: Computer Aided Verification, Berkeley, CA, USA: Springer. https://doi.org/10.1007/978-3-642-31424-7_24","ista":"Guet CC, Gupta A, Henzinger TA, Mateescu M, Sezgin A. 2012. Delayed continuous time Markov chains for genetic regulatory circuits. CAV: Computer Aided Verification, LNCS, vol. 7358, 294–309.","short":"C.C. Guet, A. Gupta, T.A. Henzinger, M. Mateescu, A. Sezgin, in:, Springer, 2012, pp. 294–309.","mla":"Guet, Calin C., et al. Delayed Continuous Time Markov Chains for Genetic Regulatory Circuits. Vol. 7358, Springer, 2012, pp. 294–309, doi:10.1007/978-3-642-31424-7_24.","chicago":"Guet, Calin C, Ashutosh Gupta, Thomas A Henzinger, Maria Mateescu, and Ali Sezgin. “Delayed Continuous Time Markov Chains for Genetic Regulatory Circuits,” 7358:294–309. Springer, 2012. https://doi.org/10.1007/978-3-642-31424-7_24."},"page":"294 - 309","project":[{"grant_number":"267989","_id":"25EE3708-B435-11E9-9278-68D0E5697425","name":"Quantitative Reactive Modeling","call_identifier":"FP7"}],"quality_controlled":"1","doi":"10.1007/978-3-642-31424-7_24","date_published":"2012-07-01T00:00:00Z","conference":{"name":"CAV: Computer Aided Verification","start_date":"2012-07-07","location":"Berkeley, CA, USA","end_date":"2012-07-13"},"language":[{"iso":"eng"}],"scopus_import":1,"month":"07","day":"01"},{"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"6496","status":"public","title":"Noise underlies switching behavior of the bacterial flagellum","intvolume":" 101","oa_version":"Published Version","type":"journal_article","abstract":[{"lang":"eng","text":"We report the switching behavior of the full bacterial flagellum system that includes the filament and the motor in wild-type Escherichia coli cells. In sorting the motor behavior by the clockwise bias, we find that the distributions of the clockwise (CW) and counterclockwise (CCW) intervals are either exponential or nonexponential with long tails. At low bias, CW intervals are exponentially distributed and CCW intervals exhibit long tails. At intermediate CW bias (0.5) both CW and CCW intervals are mainly exponentially distributed. A simple model suggests that these two distinct switching behaviors are governed by the presence of signaling noise within the chemotaxis network. Low noise yields exponentially distributed intervals, whereas large noise yields nonexponential behavior with long tails. These drastically different motor statistics may play a role in optimizing bacterial behavior for a wide range of environmental conditions."}],"issue":"10","publication":"Biophysical Journal","citation":{"short":"H. Park, P. Oikonomou, C.C. Guet, P. Cluzel, Biophysical Journal 101 (2011) 2336–2340.","mla":"Park, Heungwon, et al. “Noise Underlies Switching Behavior of the Bacterial Flagellum.” Biophysical Journal, vol. 101, no. 10, Elsevier, 2011, pp. 2336–40, doi:10.1016/j.bpj.2011.09.040.","chicago":"Park, Heungwon, Panos Oikonomou, Calin C Guet, and Philippe Cluzel. “Noise Underlies Switching Behavior of the Bacterial Flagellum.” Biophysical Journal. Elsevier, 2011. https://doi.org/10.1016/j.bpj.2011.09.040.","ama":"Park H, Oikonomou P, Guet CC, Cluzel P. Noise underlies switching behavior of the bacterial flagellum. Biophysical Journal. 2011;101(10):2336-2340. doi:10.1016/j.bpj.2011.09.040","ieee":"H. Park, P. Oikonomou, C. C. Guet, and P. Cluzel, “Noise underlies switching behavior of the bacterial flagellum,” Biophysical Journal, vol. 101, no. 10. Elsevier, pp. 2336–2340, 2011.","apa":"Park, H., Oikonomou, P., Guet, C. C., & Cluzel, P. (2011). Noise underlies switching behavior of the bacterial flagellum. Biophysical Journal. Elsevier. https://doi.org/10.1016/j.bpj.2011.09.040","ista":"Park H, Oikonomou P, Guet CC, Cluzel P. 2011. Noise underlies switching behavior of the bacterial flagellum. Biophysical Journal. 101(10), 2336–2340."},"page":"2336-2340","date_published":"2011-11-16T00:00:00Z","scopus_import":"1","day":"16","article_processing_charge":"No","year":"2011","pmid":1,"publication_status":"published","publisher":"Elsevier","department":[{"_id":"CaGu"}],"author":[{"full_name":"Park, Heungwon","last_name":"Park","first_name":"Heungwon"},{"full_name":"Oikonomou, Panos","last_name":"Oikonomou","first_name":"Panos"},{"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":"Cluzel, Philippe","first_name":"Philippe","last_name":"Cluzel"}],"date_created":"2019-05-28T11:54:29Z","date_updated":"2021-04-16T11:54:49Z","volume":101,"oa":1,"external_id":{"pmid":["22098731"]},"main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3218319/"}],"quality_controlled":"1","doi":"10.1016/j.bpj.2011.09.040","language":[{"iso":"eng"}],"month":"11","publication_identifier":{"issn":["0006-3495"]}},{"publication_status":"published","publisher":"Open Publishing Association","department":[{"_id":"ToHe"},{"_id":"CaGu"}],"year":"2010","acknowledgement":"Jérôme Feret’s contribution was partially supported by the ABSTRACTCELL ANR-Chair of Excellence. Heinz Koeppl acknowledges the support from the Swiss National Science Foundation, grant no. 200020-117975/1. Tatjana Petrov acknowledges the support from SystemsX.ch, the Swiss Initiative in Systems Biology.","date_created":"2018-12-11T12:04:47Z","date_updated":"2023-02-23T11:15:19Z","volume":40,"author":[{"full_name":"Feret, Jérôme","last_name":"Feret","first_name":"Jérôme"},{"full_name":"Henzinger, Thomas A","last_name":"Henzinger","first_name":"Thomas A","orcid":"0000−0002−2985−7724","id":"40876CD8-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Koeppl, Heinz","last_name":"Koeppl","first_name":"Heinz"},{"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":"3168"}]},"file_date_updated":"2020-07-14T12:46:14Z","publist_id":"2511","quality_controlled":"1","oa":1,"external_id":{"arxiv":["1011.0496"]},"language":[{"iso":"eng"}],"conference":{"name":"MECBIC: Membrane Computing and Biologically Inspired Process Calculi","start_date":"2010-08-23","location":"Jena, Germany","end_date":"2010-08-23"},"month":"10","ddc":["570"],"title":"Lumpability abstractions of rule-based systems","status":"public","intvolume":" 40","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"3719","file":[{"relation":"main_file","file_id":"5904","checksum":"eaaba991a86fff37606b0eb5196878e8","date_created":"2019-01-31T12:09:09Z","date_updated":"2020-07-14T12:46:14Z","access_level":"open_access","file_name":"Lumpability_abstractions_of_rule-based_systems.pdf","file_size":907155,"content_type":"application/pdf","creator":"kschuh"}],"oa_version":"Submitted Version","alternative_title":["EPTCS"],"type":"conference","abstract":[{"lang":"eng","text":"The induction of a signaling pathway is characterized by transient complex formation and mutual posttranslational modification of proteins. To faithfully capture this combinatorial process in a math- ematical model is an important challenge in systems biology. Exploiting the limited context on which most binding and modification events are conditioned, attempts have been made to reduce the com- binatorial complexity by quotienting the reachable set of molecular species, into species aggregates while preserving the deterministic semantics of the thermodynamic limit. Recently we proposed a quotienting that also preserves the stochastic semantics and that is complete in the sense that the semantics of individual species can be recovered from the aggregate semantics. In this paper we prove that this quotienting yields a sufficient condition for weak lumpability and that it gives rise to a backward Markov bisimulation between the original and aggregated transition system. We illustrate the framework on a case study of the EGF/insulin receptor crosstalk."}],"page":"142-161","citation":{"mla":"Feret, Jérôme, et al. Lumpability Abstractions of Rule-Based Systems. Vol. 40, Open Publishing Association, 2010, pp. 142–61.","short":"J. Feret, T.A. Henzinger, H. Koeppl, T. Petrov, in:, Open Publishing Association, 2010, pp. 142–161.","chicago":"Feret, Jérôme, Thomas A Henzinger, Heinz Koeppl, and Tatjana Petrov. “Lumpability Abstractions of Rule-Based Systems,” 40:142–61. Open Publishing Association, 2010.","ama":"Feret J, Henzinger TA, Koeppl H, Petrov T. Lumpability abstractions of rule-based systems. In: Vol 40. Open Publishing Association; 2010:142-161.","ista":"Feret J, Henzinger TA, Koeppl H, Petrov T. 2010. Lumpability abstractions of rule-based systems. MECBIC: Membrane Computing and Biologically Inspired Process Calculi, EPTCS, vol. 40, 142–161.","apa":"Feret, J., Henzinger, T. A., Koeppl, H., & Petrov, T. (2010). Lumpability abstractions of rule-based systems (Vol. 40, pp. 142–161). Presented at the MECBIC: Membrane Computing and Biologically Inspired Process Calculi, Jena, Germany: Open Publishing Association.","ieee":"J. Feret, T. A. Henzinger, H. Koeppl, and T. Petrov, “Lumpability abstractions of rule-based systems,” presented at the MECBIC: Membrane Computing and Biologically Inspired Process Calculi, Jena, Germany, 2010, vol. 40, pp. 142–161."},"date_published":"2010-10-30T00:00:00Z","scopus_import":1,"day":"30","has_accepted_license":"1"},{"scopus_import":1,"day":"14","has_accepted_license":"1","citation":{"ama":"Didier F, Henzinger TA, Mateescu M, Wolf V. SABRE: A tool for the stochastic analysis of biochemical reaction networks. In: IEEE; 2010:193-194. doi:10.1109/QEST.2010.33","ista":"Didier F, Henzinger TA, Mateescu M, Wolf V. 2010. SABRE: A tool for the stochastic analysis of biochemical reaction networks. QEST: Quantitative Evaluation of Systems, 193–194.","apa":"Didier, F., Henzinger, T. A., Mateescu, M., & Wolf, V. (2010). SABRE: A tool for the stochastic analysis of biochemical reaction networks (pp. 193–194). Presented at the QEST: Quantitative Evaluation of Systems, Williamsburg, USA: IEEE. https://doi.org/10.1109/QEST.2010.33","ieee":"F. Didier, T. A. Henzinger, M. Mateescu, and V. Wolf, “SABRE: A tool for the stochastic analysis of biochemical reaction networks,” presented at the QEST: Quantitative Evaluation of Systems, Williamsburg, USA, 2010, pp. 193–194.","mla":"Didier, Frédéric, et al. SABRE: A Tool for the Stochastic Analysis of Biochemical Reaction Networks. IEEE, 2010, pp. 193–94, doi:10.1109/QEST.2010.33.","short":"F. Didier, T.A. Henzinger, M. Mateescu, V. Wolf, in:, IEEE, 2010, pp. 193–194.","chicago":"Didier, Frédéric, Thomas A Henzinger, Maria Mateescu, and Verena Wolf. “SABRE: A Tool for the Stochastic Analysis of Biochemical Reaction Networks,” 193–94. IEEE, 2010. https://doi.org/10.1109/QEST.2010.33."},"page":"193 - 194","date_published":"2010-10-14T00:00:00Z","type":"conference","abstract":[{"lang":"eng","text":"The importance of stochasticity within biological systems has been shown repeatedly during the last years and has raised the need for efficient stochastic tools. We present SABRE, a tool for stochastic analysis of biochemical reaction networks. SABRE implements fast adaptive uniformization (FAU), a direct numerical approximation algorithm for computing transient solutions of biochemical reaction networks. Biochemical reactions networks represent biological systems studied at a molecular level and these reactions can be modeled as transitions of a Markov chain. SABRE accepts as input the formalism of guarded commands, which it interprets either as continuous-time or as discrete-time Markov chains. Besides operating in a stochastic mode, SABRE may also perform a deterministic analysis by directly computing a mean-field approximation of the system under study. We illustrate the different functionalities of SABRE by means of biological case studies."}],"_id":"3847","user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","status":"public","title":"SABRE: A tool for the stochastic analysis of biochemical reaction networks","ddc":["004"],"pubrep_id":"63","oa_version":"Submitted Version","file":[{"file_name":"IST-2012-63-v1+1_SABRE-A_tool_for_the_stochastic_analysis_of_biochemical_reaction_networks.pdf","access_level":"open_access","file_size":433824,"content_type":"application/pdf","creator":"system","relation":"main_file","file_id":"4726","date_created":"2018-12-12T10:09:03Z","date_updated":"2020-07-14T12:46:17Z","checksum":"38707b149d2174f01be406e794ffa849"}],"month":"10","oa":1,"quality_controlled":"1","conference":{"name":"QEST: Quantitative Evaluation of Systems","end_date":"2010-09-18","location":"Williamsburg, USA","start_date":"2010-09-15"},"doi":"10.1109/QEST.2010.33","language":[{"iso":"eng"}],"file_date_updated":"2020-07-14T12:46:17Z","publist_id":"2339","year":"2010","publication_status":"published","department":[{"_id":"ToHe"},{"_id":"CaGu"}],"publisher":"IEEE","author":[{"full_name":"Didier, Frédéric","first_name":"Frédéric","last_name":"Didier"},{"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":"Mateescu, Maria","first_name":"Maria","last_name":"Mateescu"},{"full_name":"Wolf, Verena","last_name":"Wolf","first_name":"Verena"}],"date_created":"2018-12-11T12:05:29Z","date_updated":"2021-01-12T07:52:37Z"},{"scopus_import":1,"day":"30","has_accepted_license":"1","article_processing_charge":"No","page":"118 - 127","citation":{"short":"F. Didier, T.A. Henzinger, M. Mateescu, V. Wolf, in:, IEEE, 2009, pp. 118–127.","mla":"Didier, Frédéric, et al. Fast Adaptive Uniformization of the Chemical Master Equation. Vol. 4, no. 6, IEEE, 2009, pp. 118–27, doi:10.1109/HiBi.2009.23.","chicago":"Didier, Frédéric, Thomas A Henzinger, Maria Mateescu, and Verena Wolf. “Fast Adaptive Uniformization of the Chemical Master Equation,” 4:118–27. IEEE, 2009. https://doi.org/10.1109/HiBi.2009.23.","ama":"Didier F, Henzinger TA, Mateescu M, Wolf V. Fast adaptive uniformization of the chemical master equation. In: Vol 4. IEEE; 2009:118-127. doi:10.1109/HiBi.2009.23","apa":"Didier, F., Henzinger, T. A., Mateescu, M., & Wolf, V. (2009). Fast adaptive uniformization of the chemical master equation (Vol. 4, pp. 118–127). Presented at the HIBI: High-Performance Computational Systems Biology, Trento, Italy: IEEE. https://doi.org/10.1109/HiBi.2009.23","ieee":"F. Didier, T. A. Henzinger, M. Mateescu, and V. Wolf, “Fast adaptive uniformization of the chemical master equation,” presented at the HIBI: High-Performance Computational Systems Biology, Trento, Italy, 2009, vol. 4, no. 6, pp. 118–127.","ista":"Didier F, Henzinger TA, Mateescu M, Wolf V. 2009. Fast adaptive uniformization of the chemical master equation. HIBI: High-Performance Computational Systems Biology vol. 4, 118–127."},"date_published":"2009-10-30T00:00:00Z","type":"conference","abstract":[{"lang":"eng","text":"Within systems biology there is an increasing interest in the stochastic behavior of biochemical reaction networks. An appropriate stochastic description is provided by the chemical master equation, which represents a continuous- time Markov chain (CTMC).\r\nStandard Uniformization (SU) is an efficient method for the transient analysis of CTMCs. For systems with very different time scales, such as biochemical reaction networks, SU is computationally expensive. In these cases, a variant of SU, called adaptive uniformization (AU), is known to reduce the large number of iterations needed by SU. The additional difficulty of AU is that it requires the solution of a birth process.\r\nIn this paper we present an on-the-fly variant of AU, where we improve the original algorithm for AU at the cost of a small approximation error. By means of several examples, we show that our approach is particularly well-suited for biochemical reaction networks."}],"issue":"6","title":"Fast adaptive uniformization of the chemical master equation","status":"public","ddc":["000"],"intvolume":" 4","_id":"3843","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file":[{"file_name":"2009_HIBI_Didier.pdf","access_level":"open_access","content_type":"application/pdf","file_size":222890,"creator":"dernst","relation":"main_file","file_id":"7874","date_created":"2020-05-19T16:33:55Z","date_updated":"2020-07-14T12:46:17Z","checksum":"9a3bde48f43203991a0b3c6a277c2f5b"}],"oa_version":"Submitted Version","month":"10","quality_controlled":"1","oa":1,"language":[{"iso":"eng"}],"conference":{"name":"HIBI: High-Performance Computational Systems Biology","location":"Trento, Italy","start_date":"2009-10-14","end_date":"2009-10-16"},"doi":"10.1109/HiBi.2009.23","file_date_updated":"2020-07-14T12:46:17Z","publist_id":"2348","publication_status":"published","publisher":"IEEE","department":[{"_id":"ToHe"},{"_id":"CaGu"}],"acknowledgement":"This research has been partially funded by the Swiss National Science Foundation under grant 205321-111840 and by the Cluster of Excellence on Multimodal Computing and Interaction at Saarland University.","year":"2009","date_updated":"2023-02-23T11:45:05Z","date_created":"2018-12-11T12:05:28Z","volume":4,"author":[{"full_name":"Didier, Frédéric","first_name":"Frédéric","last_name":"Didier"},{"first_name":"Thomas A","last_name":"Henzinger","id":"40876CD8-F248-11E8-B48F-1D18A9856A87","orcid":"0000−0002−2985−7724","full_name":"Henzinger, Thomas A"},{"full_name":"Mateescu, Maria","first_name":"Maria","last_name":"Mateescu","id":"3B43276C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Verena","last_name":"Wolf","full_name":"Wolf, Verena"}],"related_material":{"record":[{"id":"3842","status":"public","relation":"later_version"}]}}]