[{"publisher":"Springer Nature","_id":"11713","author":[{"first_name":"Nela","id":"42D9CABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9068-6090","full_name":"Nikolic, Nela","last_name":"Nikolic"},{"full_name":"Sauert, Martina","last_name":"Sauert","first_name":"Martina"},{"first_name":"Tanino G.","last_name":"Albanese","full_name":"Albanese, Tanino G."},{"first_name":"Isabella","last_name":"Moll","full_name":"Moll, Isabella"}],"article_processing_charge":"No","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"CaGu"}],"date_published":"2022-05-13T00:00:00Z","year":"2022","day":"13","acknowledgement":"We acknowledge the Max Perutz Labs FACS Facility together with Thomas Sauer. NN is grateful to Călin C. Guet for his support.\r\nThis work was funded by the Elise Richter grant V738 of the Austrian Science Fund (FWF), and the FWF Lise Meitner grant M1697, to NN; and by the FWF grant P22249, FWF Special Research Program RNA-REG F43 (subproject F4316), and FWF doctoral program RNA Biology (W1207), to IM. Open access funding provided by the Austrian Science Fund.","status":"public","file":[{"file_size":1545310,"date_created":"2022-08-01T09:24:42Z","access_level":"open_access","date_updated":"2022-08-01T09:24:42Z","file_id":"11714","relation":"main_file","file_name":"2022_BMCResearchNotes_Nikolic.pdf","content_type":"application/pdf","checksum":"008156e5340e9789f0f6d82bde4d347a","success":1,"creator":"dernst"}],"license":"https://creativecommons.org/licenses/by/4.0/","volume":15,"file_date_updated":"2022-08-01T09:24:42Z","article_number":"173","related_material":{"link":[{"relation":"erratum","url":"https://doi.org/10.1186/s13104-022-06152-7"}]},"keyword":["General Biochemistry","Genetics and Molecular Biology","General Medicine"],"has_accepted_license":"1","publication_identifier":{"issn":["1756-0500"]},"quality_controlled":"1","project":[{"grant_number":"V00738","call_identifier":"FWF","_id":"26956E74-B435-11E9-9278-68D0E5697425","name":"Bacterial toxin-antitoxin systems as antiphage defense mechanisms"}],"type":"journal_article","pmid":1,"citation":{"chicago":"Nikolic, Nela, Martina Sauert, Tanino G. Albanese, and Isabella Moll. “Quantifying Heterologous Gene Expression during Ectopic MazF Production in Escherichia Coli.” <i>BMC Research Notes</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1186/s13104-022-06061-9\">https://doi.org/10.1186/s13104-022-06061-9</a>.","short":"N. Nikolic, M. Sauert, T.G. Albanese, I. Moll, BMC Research Notes 15 (2022).","apa":"Nikolic, N., Sauert, M., Albanese, T. G., &#38; Moll, I. (2022). Quantifying heterologous gene expression during ectopic MazF production in Escherichia coli. <i>BMC Research Notes</i>. Springer Nature. <a href=\"https://doi.org/10.1186/s13104-022-06061-9\">https://doi.org/10.1186/s13104-022-06061-9</a>","ieee":"N. Nikolic, M. Sauert, T. G. Albanese, and I. Moll, “Quantifying heterologous gene expression during ectopic MazF production in Escherichia coli,” <i>BMC Research Notes</i>, vol. 15. Springer Nature, 2022.","ama":"Nikolic N, Sauert M, Albanese TG, Moll I. Quantifying heterologous gene expression during ectopic MazF production in Escherichia coli. <i>BMC Research Notes</i>. 2022;15. doi:<a href=\"https://doi.org/10.1186/s13104-022-06061-9\">10.1186/s13104-022-06061-9</a>","ista":"Nikolic N, Sauert M, Albanese TG, Moll I. 2022. Quantifying heterologous gene expression during ectopic MazF production in Escherichia coli. BMC Research Notes. 15, 173.","mla":"Nikolic, Nela, et al. “Quantifying Heterologous Gene Expression during Ectopic MazF Production in Escherichia Coli.” <i>BMC Research Notes</i>, vol. 15, 173, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1186/s13104-022-06061-9\">10.1186/s13104-022-06061-9</a>."},"article_type":"letter_note","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"scopus_import":"1","publication_status":"published","date_updated":"2025-04-14T09:24:53Z","language":[{"iso":"eng"}],"oa_version":"Published Version","doi":"10.1186/s13104-022-06061-9","abstract":[{"lang":"eng","text":"Objective: MazF is a sequence-specific endoribonuclease-toxin of the MazEF toxin–antitoxin system. MazF cleaves single-stranded ribonucleic acid (RNA) regions at adenine–cytosine–adenine (ACA) sequences in the bacterium Escherichia coli. The MazEF system has been used in various biotechnology and synthetic biology applications. In this study, we infer how ectopic mazF overexpression affects production of heterologous proteins. To this end, we quantified the levels of fluorescent proteins expressed in E. coli from reporters translated from the ACA-containing or ACA-less messenger RNAs (mRNAs). Additionally, we addressed the impact of the 5′-untranslated region of these reporter mRNAs under the same conditions by comparing expression from mRNAs that comprise (canonical mRNA) or lack this region (leaderless mRNA).\r\nResults: Flow cytometry analysis indicates that during mazF overexpression, fluorescent proteins are translated from the canonical as well as leaderless mRNAs. Our analysis further indicates that longer mazF overexpression generally increases the concentration of fluorescent proteins translated from ACA-less mRNAs, however it also substantially increases bacterial population heterogeneity. Finally, our results suggest that the strength and duration of mazF overexpression should be optimized for each experimental setup, to maximize the heterologous protein production and minimize the amount of phenotypic heterogeneity in bacterial populations, which is unfavorable in biotechnological processes."}],"title":"Quantifying heterologous gene expression during ectopic MazF production in Escherichia coli","external_id":{"pmid":["35562780"]},"month":"05","ddc":["570"],"corr_author":"1","date_created":"2022-08-01T09:04:27Z","publication":"BMC Research Notes","oa":1,"intvolume":"        15"},{"related_material":{"record":[{"status":"public","relation":"earlier_version","id":"10316"}]},"article_number":"e78995","has_accepted_license":"1","publication_identifier":{"eissn":["2050-084X"]},"pmid":1,"quality_controlled":"1","project":[{"grant_number":"724373","name":"Cellular Navigation Along Spatial Gradients","_id":"25FE9508-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"name":"Mechanical adaptation of lamellipodial actin","_id":"26018E70-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"P29911"}],"type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","citation":{"chicago":"Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch, Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/eLife.78995\">https://doi.org/10.7554/eLife.78995</a>.","short":"K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt, ELife 11 (2022).","ieee":"K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M. K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","apa":"Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., &#38; Sixt, M. K. (2022). Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.78995\">https://doi.org/10.7554/eLife.78995</a>","ista":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. 2022. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. eLife. 11, e78995.","ama":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/eLife.78995\">10.7554/eLife.78995</a>","mla":"Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>ELife</i>, vol. 11, e78995, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/eLife.78995\">10.7554/eLife.78995</a>."},"_id":"11843","author":[{"orcid":"0000-0003-3768-877X","first_name":"Kathrin","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","last_name":"Tomasek","full_name":"Tomasek, Kathrin"},{"full_name":"Leithner, Alexander F","last_name":"Leithner","first_name":"Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1073-744X"},{"full_name":"Glatzová, Ivana","last_name":"Glatzová","first_name":"Ivana","id":"727b3c7d-4939-11ec-89b3-b9b0750ab74d"},{"full_name":"Lukesch, Michael S.","last_name":"Lukesch","first_name":"Michael S."},{"orcid":"0000-0001-6220-2052","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","full_name":"Guet, Calin C"},{"last_name":"Sixt","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"Yes","publisher":"eLife Sciences Publications","date_published":"2022-07-26T00:00:00Z","day":"26","year":"2022","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"MiSi"},{"_id":"CaGu"}],"acknowledgement":"We thank Ulrich Dobrindt for providing UPEC strains CFT073, UTI89, and 536, Frank Assen, Vlad Gavra, Maximilian Götz, Bor Kavčič, Jonna Alanko, and Eva Kiermaier for help with experiments and Robert Hauschild, Julian Stopp, and Saren Tasciyan for help with data analysis. We thank the IST Austria Scientific Service Units, especially the Bioimaging facility, the Preclinical facility and the Electron microscopy facility for technical support, Jakob Wallner and all members of the Guet and Sixt lab for fruitful discussions and Daria Siekhaus for critically reading the manuscript. This work was supported by grants from the Austrian Research Promotion Agency (FEMtech 868984) to IG, the European Research Council (CoG 724373), and the Austrian Science Fund (FWF P29911) to MS.","volume":11,"file_date_updated":"2022-08-16T08:57:37Z","ec_funded":1,"status":"public","file":[{"success":1,"creator":"cchlebak","content_type":"application/pdf","file_name":"2022_eLife_Tomasek.pdf","checksum":"002a3c7c7ea5caa9af9cfbea308f6ea4","relation":"main_file","file_id":"11861","date_updated":"2022-08-16T08:57:37Z","access_level":"open_access","file_size":2057577,"date_created":"2022-08-16T08:57:37Z"}],"corr_author":"1","month":"07","ddc":["570"],"isi":1,"date_created":"2022-08-14T22:01:46Z","publication":"eLife","oa":1,"intvolume":"        11","date_updated":"2025-04-15T07:17:32Z","publication_status":"published","scopus_import":"1","language":[{"iso":"eng"}],"oa_version":"Published Version","doi":"10.7554/eLife.78995","external_id":{"pmid":["35881547"],"isi":["000838410200001"]},"abstract":[{"lang":"eng","text":"A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on mouse dendritic cells (DCs) as a binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of the pathogenic strain CFT073 to CD14 reduced DC migration by overactivation of integrins and blunted expression of co-stimulatory molecules by overactivating the NFAT (nuclear factor of activated T-cells) pathway, both rate-limiting factors of T cell activation. This response was binary at the single-cell level, but averaged in larger populations exposed to both piliated and non-piliated pathogens, presumably via the exchange of immunomodulatory cytokines. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease."}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"title":"Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14"},{"external_id":{"pmid":["36546673"],"isi":["000912674700001"]},"abstract":[{"text":"Together, copy-number and point mutations form the basis for most evolutionary novelty, through the process of gene duplication and divergence. While a plethora of genomic data reveals the long-term fate of diverging coding sequences and their cis-regulatory elements, little is known about the early dynamics around the duplication event itself. In microorganisms, selection for increased gene expression often drives the expansion of gene copy-number mutations, which serves as a crude adaptation, prior to divergence through refining point mutations. Using a simple synthetic genetic reporter system that can distinguish between copy-number and point mutations, we study their early and transient adaptive dynamics in real time in Escherichia coli. We find two qualitatively different routes of adaptation, depending on the level of functional improvement needed. In conditions of high gene expression demand, the two mutation types occur as a combination. However, under low gene expression demand, copy-number and point mutations are mutually exclusive; here, owing to their higher frequency, adaptation is dominated by copy-number mutations, in a process we term amplification hindrance. Ultimately, due to high reversal rates and pleiotropic cost, copy-number mutations may not only serve as a crude and transient adaptation, but also constrain sequence divergence over evolutionary time scales.","lang":"eng"}],"title":"Adaptation dynamics between copynumber and point mutations","doi":"10.7554/ELIFE.82240","language":[{"iso":"eng"}],"oa_version":"Published Version","publication_status":"published","date_updated":"2025-03-06T14:03:50Z","scopus_import":"1","intvolume":"        11","oa":1,"date_created":"2023-01-22T23:00:55Z","publication":"eLife","corr_author":"1","month":"12","ddc":["570"],"isi":1,"volume":11,"file_date_updated":"2023-01-23T08:56:21Z","status":"public","file":[{"checksum":"9321fd5f06ff59d5e2d33daee84b3da1","file_name":"2022_eLife_Tomanek.pdf","content_type":"application/pdf","success":1,"creator":"dernst","file_id":"12338","relation":"main_file","access_level":"open_access","date_updated":"2023-01-23T08:56:21Z","date_created":"2023-01-23T08:56:21Z","file_size":8835954}],"acknowledgement":"We are grateful to N Barton, F Kondrashov, M Lagator, M Pleska, R Roemhild, D Siekhaus, and G\r\nTkacik for input on the manuscript and to K Tomasek for help with flow cytometry.","date_published":"2022-12-22T00:00:00Z","year":"2022","day":"22","department":[{"_id":"CaGu"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"12333","author":[{"full_name":"Tomanek, Isabella","last_name":"Tomanek","id":"3981F020-F248-11E8-B48F-1D18A9856A87","first_name":"Isabella","orcid":"0000-0001-6197-363X"},{"last_name":"Guet","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"No","publisher":"eLife Sciences Publications","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"citation":{"mla":"Tomanek, Isabella, and Calin C. Guet. “Adaptation Dynamics between Copynumber and Point Mutations.” <i>ELife</i>, vol. 11, e82240, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/ELIFE.82240\">10.7554/ELIFE.82240</a>.","apa":"Tomanek, I., &#38; Guet, C. C. (2022). Adaptation dynamics between copynumber and point mutations. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/ELIFE.82240\">https://doi.org/10.7554/ELIFE.82240</a>","ieee":"I. Tomanek and C. C. Guet, “Adaptation dynamics between copynumber and point mutations,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","short":"I. Tomanek, C.C. Guet, ELife 11 (2022).","chicago":"Tomanek, Isabella, and Calin C Guet. “Adaptation Dynamics between Copynumber and Point Mutations.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/ELIFE.82240\">https://doi.org/10.7554/ELIFE.82240</a>.","ista":"Tomanek I, Guet CC. 2022. Adaptation dynamics between copynumber and point mutations. eLife. 11, e82240.","ama":"Tomanek I, Guet CC. Adaptation dynamics between copynumber and point mutations. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/ELIFE.82240\">10.7554/ELIFE.82240</a>"},"pmid":1,"quality_controlled":"1","type":"journal_article","has_accepted_license":"1","publication_identifier":{"eissn":["2050-084X"]},"related_material":{"record":[{"id":"12339","status":"public","relation":"research_data"}],"link":[{"relation":"software","url":"https://doi.org/10.5281/zenodo.6974122"}]},"article_number":"e82240"},{"citation":{"mla":"Tomanek, Isabella, and Calin C. Guet. <i>Flow Cytometry YFP and CFP Data and Deep Sequencing Data of Populations Evolving in Galactose</i>. Dryad, 2022, doi:<a href=\"https://doi.org/10.5061/dryad.rfj6q57ds\">10.5061/dryad.rfj6q57ds</a>.","chicago":"Tomanek, Isabella, and Calin C Guet. “Flow Cytometry YFP and CFP Data and Deep Sequencing Data of Populations Evolving in Galactose.” Dryad, 2022. <a href=\"https://doi.org/10.5061/dryad.rfj6q57ds\">https://doi.org/10.5061/dryad.rfj6q57ds</a>.","short":"I. Tomanek, C.C. Guet, (2022).","ieee":"I. Tomanek and C. C. Guet, “Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose.” Dryad, 2022.","apa":"Tomanek, I., &#38; Guet, C. C. (2022). Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose. Dryad. <a href=\"https://doi.org/10.5061/dryad.rfj6q57ds\">https://doi.org/10.5061/dryad.rfj6q57ds</a>","ama":"Tomanek I, Guet CC. Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose. 2022. doi:<a href=\"https://doi.org/10.5061/dryad.rfj6q57ds\">10.5061/dryad.rfj6q57ds</a>","ista":"Tomanek I, Guet CC. 2022. Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose, Dryad, <a href=\"https://doi.org/10.5061/dryad.rfj6q57ds\">10.5061/dryad.rfj6q57ds</a>."},"type":"research_data_reference","oa":1,"date_created":"2023-01-23T09:00:37Z","corr_author":"1","related_material":{"record":[{"id":"12333","status":"public","relation":"used_in_publication"}]},"month":"12","ddc":["570"],"main_file_link":[{"open_access":"1","url":"https://doi.org/10.5061/dryad.rfj6q57ds"}],"title":"Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose","status":"public","abstract":[{"text":"Copy-number and point mutations form the basis for most evolutionary novelty through the process of gene duplication and divergence. While a plethora of genomic sequence data reveals the long-term fate of diverging coding sequences and their cis-regulatory elements, little is known about the early dynamics around the duplication event itself. In microorganisms, selection for increased gene expression often drives the expansion of gene copy-number mutations, which serves as a crude adaptation, prior to divergence through refining point mutations. Using a simple synthetic genetic system that allows us to distinguish copy-number and point mutations, we study their early and transient adaptive dynamics in real-time in Escherichia coli. We find two qualitatively different routes of adaptation depending on the level of functional improvement selected for: In conditions of high gene expression demand, the two types of mutations occur as a combination. Under low gene expression demand, negative epistasis between the two types of mutations renders them mutually exclusive. Thus, owing to their higher frequency, adaptation is dominated by copy-number mutations. Ultimately, due to high rates of reversal and pleiotropic cost, copy-number mutations may not only serve as a crude and transient adaptation but also constrain sequence divergence over evolutionary time scales.","lang":"eng"}],"doi":"10.5061/dryad.rfj6q57ds","date_published":"2022-12-23T00:00:00Z","oa_version":"Published Version","year":"2022","day":"23","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"CaGu"}],"date_updated":"2025-03-06T14:03:50Z","_id":"12339","author":[{"last_name":"Tomanek","full_name":"Tomanek, Isabella","orcid":"0000-0001-6197-363X","first_name":"Isabella","id":"3981F020-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Guet","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C"}],"article_processing_charge":"No","publisher":"Dryad"},{"acknowledgement":"We thank Hande Acar, Nicholas H Barton, Rok Grah, Tiago Paixao, Maros Pleska, Anna Staron, and Murat Tugrul for insightful comments and input on the manuscript. This work was supported by: Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant number 216779/Z/19/Z) to ML; IPC Grant from IST Austria to ML and SS; European Research Council Funding Programme 7 (2007–2013, grant agreement number 648440) to JPB.","file":[{"file_size":5604343,"date_created":"2022-02-07T07:14:09Z","access_level":"open_access","date_updated":"2022-02-07T07:14:09Z","file_id":"10739","relation":"main_file","content_type":"application/pdf","file_name":"2022_ELife_Lagator.pdf","checksum":"decdcdf600ff51e9a9703b49ca114170","success":1,"creator":"cchlebak"}],"status":"public","ec_funded":1,"file_date_updated":"2022-02-07T07:14:09Z","volume":11,"publisher":"eLife Sciences Publications","_id":"10736","author":[{"id":"345D25EC-F248-11E8-B48F-1D18A9856A87","first_name":"Mato","full_name":"Lagator, Mato","last_name":"Lagator"},{"id":"35F0286E-F248-11E8-B48F-1D18A9856A87","first_name":"Srdjan","last_name":"Sarikas","full_name":"Sarikas, Srdjan"},{"last_name":"Steinrück","full_name":"Steinrück, Magdalena","orcid":"0000-0003-1229-9719","id":"2C023F40-F248-11E8-B48F-1D18A9856A87","first_name":"Magdalena"},{"full_name":"Toledo-Aparicio, David","last_name":"Toledo-Aparicio","first_name":"David"},{"full_name":"Bollback, Jonathan P","last_name":"Bollback","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","first_name":"Jonathan P","orcid":"0000-0002-4624-4612"},{"last_name":"Guet","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C"},{"last_name":"Tkačik","full_name":"Tkačik, Gašper","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gašper"}],"article_processing_charge":"No","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"NiBa"}],"day":"26","year":"2022","date_published":"2022-01-26T00:00:00Z","type":"journal_article","project":[{"grant_number":"648440","_id":"2578D616-B435-11E9-9278-68D0E5697425","name":"Selective Barriers to Horizontal Gene Transfer","call_identifier":"H2020"}],"quality_controlled":"1","pmid":1,"citation":{"mla":"Lagator, Mato, et al. “Predicting Bacterial Promoter Function and Evolution from Random Sequences.” <i>ELife</i>, vol. 11, e64543, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/eLife.64543\">10.7554/eLife.64543</a>.","ama":"Lagator M, Sarikas S, Steinrück M, et al. Predicting bacterial promoter function and evolution from random sequences. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/eLife.64543\">10.7554/eLife.64543</a>","ista":"Lagator M, Sarikas S, Steinrück M, Toledo-Aparicio D, Bollback JP, Guet CC, Tkačik G. 2022. Predicting bacterial promoter function and evolution from random sequences. eLife. 11, e64543.","chicago":"Lagator, Mato, Srdjan Sarikas, Magdalena Steinrück, David Toledo-Aparicio, Jonathan P Bollback, Calin C Guet, and Gašper Tkačik. “Predicting Bacterial Promoter Function and Evolution from Random Sequences.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/eLife.64543\">https://doi.org/10.7554/eLife.64543</a>.","short":"M. Lagator, S. Sarikas, M. Steinrück, D. Toledo-Aparicio, J.P. Bollback, C.C. Guet, G. Tkačik, ELife 11 (2022).","ieee":"M. Lagator <i>et al.</i>, “Predicting bacterial promoter function and evolution from random sequences,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","apa":"Lagator, M., Sarikas, S., Steinrück, M., Toledo-Aparicio, D., Bollback, J. P., Guet, C. C., &#38; Tkačik, G. (2022). Predicting bacterial promoter function and evolution from random sequences. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.64543\">https://doi.org/10.7554/eLife.64543</a>"},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","article_number":"e64543","publication_identifier":{"eissn":["2050-084X"]},"has_accepted_license":"1","doi":"10.7554/eLife.64543","title":"Predicting bacterial promoter function and evolution from random sequences","abstract":[{"lang":"eng","text":"Predicting function from sequence is a central problem of biology. Currently, this is possible only locally in a narrow mutational neighborhood around a wildtype sequence rather than globally from any sequence. Using random mutant libraries, we developed a biophysical model that accounts for multiple features of σ70 binding bacterial promoters to predict constitutive gene expression levels from any sequence. We experimentally and theoretically estimated that 10–20% of random sequences lead to expression and ~80% of non-expressing sequences are one mutation away from a functional promoter. The potential for generating expression from random sequences is so pervasive that selection acts against σ70-RNA polymerase binding sites even within inter-genic, promoter-containing regions. This pervasiveness of σ70-binding sites implies that emergence of promoters is not the limiting step in gene regulatory evolution. Ultimately, the inclusion of novel features of promoter function into a mechanistic model enabled not only more accurate predictions of gene expression levels, but also identified that promoters evolve more rapidly than previously thought."}],"external_id":{"isi":["000751104400001"],"pmid":["35080492"]},"scopus_import":"1","date_updated":"2025-03-31T16:00:23Z","publication_status":"published","oa_version":"Published Version","language":[{"iso":"eng"}],"oa":1,"intvolume":"        11","ddc":["576"],"isi":1,"month":"01","corr_author":"1","publication":"eLife","date_created":"2022-02-06T23:01:32Z"},{"intvolume":"        20","isi":1,"month":"08","publication":"Nature Reviews Microbiology","page":"478-490","date_created":"2022-03-04T04:33:49Z","doi":"10.1038/s41579-022-00700-5","title":"The physiology and genetics of bacterial responses to antibiotic combinations","abstract":[{"lang":"eng","text":"Several promising strategies based on combining or cycling different antibiotics have been proposed to increase efficacy and counteract resistance evolution, but we still lack a deep understanding of the physiological responses and genetic mechanisms that underlie antibiotic interactions and the clinical applicability of these strategies. In antibiotic-exposed bacteria, the combined effects of physiological stress responses and emerging resistance mutations (occurring at different time scales) generate complex and often unpredictable dynamics. In this Review, we present our current understanding of bacterial cell physiology and genetics of responses to antibiotics. We emphasize recently discovered mechanisms of synergistic and antagonistic drug interactions, hysteresis in temporal interactions between antibiotics that arise from microbial physiology and interactions between antibiotics and resistance mutations that can cause collateral sensitivity or cross-resistance. We discuss possible connections between the different phenomena and indicate relevant research directions. A better and more unified understanding of drug and genetic interactions is likely to advance antibiotic therapy."}],"external_id":{"isi":["000763891900001"],"pmid":["35241807"]},"scopus_import":"1","publication_status":"published","date_updated":"2023-08-02T14:41:44Z","oa_version":"None","language":[{"iso":"eng"}],"type":"journal_article","quality_controlled":"1","pmid":1,"citation":{"ama":"Römhild R, Bollenbach MT, Andersson DI. The physiology and genetics of bacterial responses to antibiotic combinations. <i>Nature Reviews Microbiology</i>. 2022;20:478-490. doi:<a href=\"https://doi.org/10.1038/s41579-022-00700-5\">10.1038/s41579-022-00700-5</a>","ista":"Römhild R, Bollenbach MT, Andersson DI. 2022. The physiology and genetics of bacterial responses to antibiotic combinations. Nature Reviews Microbiology. 20, 478–490.","short":"R. Römhild, M.T. Bollenbach, D.I. Andersson, Nature Reviews Microbiology 20 (2022) 478–490.","chicago":"Römhild, Roderich, Mark Tobias Bollenbach, and Dan I. Andersson. “The Physiology and Genetics of Bacterial Responses to Antibiotic Combinations.” <i>Nature Reviews Microbiology</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41579-022-00700-5\">https://doi.org/10.1038/s41579-022-00700-5</a>.","ieee":"R. Römhild, M. T. Bollenbach, and D. I. Andersson, “The physiology and genetics of bacterial responses to antibiotic combinations,” <i>Nature Reviews Microbiology</i>, vol. 20. Springer Nature, pp. 478–490, 2022.","apa":"Römhild, R., Bollenbach, M. T., &#38; Andersson, D. I. (2022). The physiology and genetics of bacterial responses to antibiotic combinations. <i>Nature Reviews Microbiology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41579-022-00700-5\">https://doi.org/10.1038/s41579-022-00700-5</a>","mla":"Römhild, Roderich, et al. “The Physiology and Genetics of Bacterial Responses to Antibiotic Combinations.” <i>Nature Reviews Microbiology</i>, vol. 20, Springer Nature, 2022, pp. 478–90, doi:<a href=\"https://doi.org/10.1038/s41579-022-00700-5\">10.1038/s41579-022-00700-5</a>."},"article_type":"review","publication_identifier":{"eissn":["1740-1534"],"issn":["1740-1526"]},"keyword":["General Immunology and Microbiology","Microbiology","Infectious Diseases"],"acknowledgement":"The authors thank B. Kavčič and H. Schulenburg for constructive feedback on the manuscript.","status":"public","volume":20,"publisher":"Springer Nature","_id":"10812","article_processing_charge":"No","author":[{"full_name":"Römhild, Roderich","last_name":"Römhild","id":"68E56E44-62B0-11EA-B963-444F3DDC885E","first_name":"Roderich","orcid":"0000-0001-9480-5261"},{"full_name":"Bollenbach, Mark Tobias","last_name":"Bollenbach","first_name":"Mark Tobias","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4398-476X"},{"first_name":"Dan I.","last_name":"Andersson","full_name":"Andersson, Dan I."}],"department":[{"_id":"CaGu"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","year":"2022","day":"01","date_published":"2022-08-01T00:00:00Z"},{"article_number":"e1009950","issue":"3","related_material":{"link":[{"relation":"software","url":"https://gitlab.pasteur.fr/adavidov/inferencelnakf"}]},"has_accepted_license":"1","publication_identifier":{"issn":["1553-734X"],"eissn":["1553-7358"]},"quality_controlled":"1","type":"journal_article","pmid":1,"citation":{"ama":"Davidović A, Chait RP, Batt G, Ruess J. Parameter inference for stochastic biochemical models from perturbation experiments parallelised at the single cell level. <i>PLoS Computational Biology</i>. 2022;18(3). doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1009950\">10.1371/journal.pcbi.1009950</a>","ista":"Davidović A, Chait RP, Batt G, Ruess J. 2022. Parameter inference for stochastic biochemical models from perturbation experiments parallelised at the single cell level. PLoS Computational Biology. 18(3), e1009950.","chicago":"Davidović, Anđela, Remy P Chait, Gregory Batt, and Jakob Ruess. “Parameter Inference for Stochastic Biochemical Models from Perturbation Experiments Parallelised at the Single Cell Level.” <i>PLoS Computational Biology</i>. Public Library of Science, 2022. <a href=\"https://doi.org/10.1371/journal.pcbi.1009950\">https://doi.org/10.1371/journal.pcbi.1009950</a>.","short":"A. Davidović, R.P. Chait, G. Batt, J. Ruess, PLoS Computational Biology 18 (2022).","ieee":"A. Davidović, R. P. Chait, G. Batt, and J. Ruess, “Parameter inference for stochastic biochemical models from perturbation experiments parallelised at the single cell level,” <i>PLoS Computational Biology</i>, vol. 18, no. 3. Public Library of Science, 2022.","apa":"Davidović, A., Chait, R. P., Batt, G., &#38; Ruess, J. (2022). Parameter inference for stochastic biochemical models from perturbation experiments parallelised at the single cell level. <i>PLoS Computational Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pcbi.1009950\">https://doi.org/10.1371/journal.pcbi.1009950</a>","mla":"Davidović, Anđela, et al. “Parameter Inference for Stochastic Biochemical Models from Perturbation Experiments Parallelised at the Single Cell Level.” <i>PLoS Computational Biology</i>, vol. 18, no. 3, e1009950, Public Library of Science, 2022, doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1009950\">10.1371/journal.pcbi.1009950</a>."},"article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"publisher":"Public Library of Science","author":[{"last_name":"Davidović","full_name":"Davidović, Anđela","first_name":"Anđela"},{"id":"3464AE84-F248-11E8-B48F-1D18A9856A87","first_name":"Remy P","orcid":"0000-0003-0876-3187","full_name":"Chait, Remy P","last_name":"Chait"},{"last_name":"Batt","full_name":"Batt, Gregory","first_name":"Gregory"},{"full_name":"Ruess, Jakob","last_name":"Ruess","first_name":"Jakob","id":"4A245D00-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1615-3282"}],"_id":"10939","article_processing_charge":"No","department":[{"_id":"CaGu"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","date_published":"2022-03-18T00:00:00Z","day":"18","year":"2022","acknowledgement":"We thank Virgile Andreani for useful discussions about the model and parameter inference. We thank Johan Paulsson and Jeffrey J Tabor for kind gifts of plasmids. R was supported by the ANR grant CyberCircuits (ANR-18-CE91-0002). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","status":"public","file":[{"file_id":"10947","relation":"main_file","checksum":"458ef542761fb714ced214f240daf6b2","content_type":"application/pdf","file_name":"2022_PLoSCompBio_Davidovic.pdf","success":1,"creator":"dernst","file_size":2958642,"date_created":"2022-04-04T10:14:39Z","access_level":"open_access","date_updated":"2022-04-04T10:14:39Z"}],"file_date_updated":"2022-04-04T10:14:39Z","volume":18,"month":"03","isi":1,"ddc":["570","000"],"date_created":"2022-04-03T22:01:42Z","publication":"PLoS Computational Biology","oa":1,"intvolume":"        18","scopus_import":"1","publication_status":"published","date_updated":"2025-09-09T14:29:53Z","language":[{"iso":"eng"}],"oa_version":"Published Version","doi":"10.1371/journal.pcbi.1009950","title":"Parameter inference for stochastic biochemical models from perturbation experiments parallelised at the single cell level","abstract":[{"lang":"eng","text":"Understanding and characterising biochemical processes inside single cells requires experimental platforms that allow one to perturb and observe the dynamics of such processes as well as computational methods to build and parameterise models from the collected data. Recent progress with experimental platforms and optogenetics has made it possible to expose each cell in an experiment to an individualised input and automatically record cellular responses over days with fine time resolution. However, methods to infer parameters of stochastic kinetic models from single-cell longitudinal data have generally been developed under the assumption that experimental data is sparse and that responses of cells to at most a few different input perturbations can be observed. Here, we investigate and compare different approaches for calculating parameter likelihoods of single-cell longitudinal data based on approximations of the chemical master equation (CME) with a particular focus on coupling the linear noise approximation (LNA) or moment closure methods to a Kalman filter. We show that, as long as cells are measured sufficiently frequently, coupling the LNA to a Kalman filter allows one to accurately approximate likelihoods and to infer model parameters from data even in cases where the LNA provides poor approximations of the CME. Furthermore, the computational cost of filtering-based iterative likelihood evaluation scales advantageously in the number of measurement times and different input perturbations and is thus ideally suited for data obtained from modern experimental platforms. To demonstrate the practical usefulness of these results, we perform an experiment in which single cells, equipped with an optogenetic gene expression system, are exposed to various different light-input sequences and measured at several hundred time points and use parameter inference based on iterative likelihood evaluation to parameterise a stochastic model of the system."}],"external_id":{"isi":["001044208400004"],"pmid":["35303737"]}},{"isi":1,"ddc":["570"],"month":"04","publication":"Communications Biology","date_created":"2022-05-01T22:01:41Z","oa":1,"intvolume":"         5","scopus_import":"1","date_updated":"2023-08-03T06:45:26Z","publication_status":"published","oa_version":"Published Version","language":[{"iso":"eng"}],"doi":"10.1038/s42003-022-03336-6","title":"Nutrient and salt depletion synergistically boosts glucose metabolism in individual Escherichia coli cells","abstract":[{"text":"The interaction between a cell and its environment shapes fundamental intracellular processes such as cellular metabolism. In most cases growth rate is treated as a proximal metric for understanding the cellular metabolic status. However, changes in growth rate might not reflect metabolic variations in individuals responding to environmental fluctuations. Here we use single-cell microfluidics-microscopy combined with transcriptomics, proteomics and mathematical modelling to quantify the accumulation of glucose within Escherichia coli cells. In contrast to the current consensus, we reveal that environmental conditions which are comparatively unfavourable for growth, where both nutrients and salinity are depleted, increase glucose accumulation rates in individual bacteria and population subsets. We find that these changes in metabolic function are underpinned by variations at the translational and posttranslational level but not at the transcriptional level and are not dictated by changes in cell size. The metabolic response-characteristics identified greatly advance our fundamental understanding of the interactions between bacteria and their environment and have important ramifications when investigating cellular processes where salinity plays an important role.","lang":"eng"}],"external_id":{"pmid":["35444215"],"isi":["000784143400001"]},"article_number":"385","publication_identifier":{"eissn":["2399-3642"]},"has_accepted_license":"1","type":"journal_article","quality_controlled":"1","pmid":1,"citation":{"ama":"Glover G, Voliotis M, Łapińska U, et al. Nutrient and salt depletion synergistically boosts glucose metabolism in individual Escherichia coli cells. <i>Communications Biology</i>. 2022;5. doi:<a href=\"https://doi.org/10.1038/s42003-022-03336-6\">10.1038/s42003-022-03336-6</a>","ista":"Glover G, Voliotis M, Łapińska U, Invergo BM, Soanes D, O’Neill P, Moore K, Nikolic N, Petrov P, Milner DS, Roy S, Heesom K, Richards TA, Tsaneva-Atanasova K, Pagliara S. 2022. Nutrient and salt depletion synergistically boosts glucose metabolism in individual Escherichia coli cells. Communications Biology. 5, 385.","apa":"Glover, G., Voliotis, M., Łapińska, U., Invergo, B. M., Soanes, D., O’Neill, P., … Pagliara, S. (2022). Nutrient and salt depletion synergistically boosts glucose metabolism in individual Escherichia coli cells. <i>Communications Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s42003-022-03336-6\">https://doi.org/10.1038/s42003-022-03336-6</a>","ieee":"G. Glover <i>et al.</i>, “Nutrient and salt depletion synergistically boosts glucose metabolism in individual Escherichia coli cells,” <i>Communications Biology</i>, vol. 5. Springer Nature, 2022.","short":"G. Glover, M. Voliotis, U. Łapińska, B.M. Invergo, D. Soanes, P. O’Neill, K. Moore, N. Nikolic, P. Petrov, D.S. Milner, S. Roy, K. Heesom, T.A. Richards, K. Tsaneva-Atanasova, S. Pagliara, Communications Biology 5 (2022).","chicago":"Glover, Georgina, Margaritis Voliotis, Urszula Łapińska, Brandon M. Invergo, Darren Soanes, Paul O’Neill, Karen Moore, et al. “Nutrient and Salt Depletion Synergistically Boosts Glucose Metabolism in Individual Escherichia Coli Cells.” <i>Communications Biology</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s42003-022-03336-6\">https://doi.org/10.1038/s42003-022-03336-6</a>.","mla":"Glover, Georgina, et al. “Nutrient and Salt Depletion Synergistically Boosts Glucose Metabolism in Individual Escherichia Coli Cells.” <i>Communications Biology</i>, vol. 5, 385, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1038/s42003-022-03336-6\">10.1038/s42003-022-03336-6</a>."},"article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"publisher":"Springer Nature","author":[{"full_name":"Glover, Georgina","last_name":"Glover","first_name":"Georgina"},{"first_name":"Margaritis","last_name":"Voliotis","full_name":"Voliotis, Margaritis"},{"last_name":"Łapińska","full_name":"Łapińska, Urszula","first_name":"Urszula"},{"full_name":"Invergo, Brandon M.","last_name":"Invergo","first_name":"Brandon M."},{"first_name":"Darren","full_name":"Soanes, Darren","last_name":"Soanes"},{"first_name":"Paul","last_name":"O’Neill","full_name":"O’Neill, Paul"},{"full_name":"Moore, Karen","last_name":"Moore","first_name":"Karen"},{"orcid":"0000-0001-9068-6090","first_name":"Nela","id":"42D9CABC-F248-11E8-B48F-1D18A9856A87","last_name":"Nikolic","full_name":"Nikolic, Nela"},{"last_name":"Petrov","full_name":"Petrov, Peter","first_name":"Peter"},{"first_name":"David S.","last_name":"Milner","full_name":"Milner, David S."},{"last_name":"Roy","full_name":"Roy, Sumita","first_name":"Sumita"},{"first_name":"Kate","last_name":"Heesom","full_name":"Heesom, Kate"},{"full_name":"Richards, Thomas A.","last_name":"Richards","first_name":"Thomas A."},{"full_name":"Tsaneva-Atanasova, Krasimira","last_name":"Tsaneva-Atanasova","first_name":"Krasimira"},{"first_name":"Stefano","last_name":"Pagliara","full_name":"Pagliara, Stefano"}],"_id":"11339","article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"CaGu"}],"year":"2022","day":"20","date_published":"2022-04-20T00:00:00Z","acknowledgement":"G.G. was supported by an EPSRC DTP PhD studentship (EP/M506527/1). M.V. and K.T.A. gratefully acknowledge financial support from the EPSRC (EP/N014391/1). U.L. was supported through a BBSRC grant (BB/V008021/1) and an MRC Proximity to Discovery EXCITEME2 grant (MCPC17189). This work was further supported by a Royal Society Research Grant (RG180007) awarded to S.P. and a QUEX Initiator grant awarded to S.P. and K.T.A.. D.S.M., T.A.R. and S.P.’s work in this area is also supported by a Marie Skłodowska-Curie project SINGEK (H2020-MSCA-ITN-2015-675752) and the Gordon and Betty Moore Foundation Marine Microbiology Initiative (GBMF5514). B.M.I. acknowledges support from a Wellcome Trust Institutional Strategic Support Award to the University of Exeter (204909/Z/16/Z). This project utilised equipment funded by the Wellcome Trust Institutional Strategic Support Fund (WT097835MF), Wellcome Trust Multi User Equipment Award (WT101650MA) and BBSRC LOLA award (BB/K003240/1).","file":[{"date_updated":"2022-05-02T06:26:26Z","access_level":"open_access","file_size":2827723,"date_created":"2022-05-02T06:26:26Z","success":1,"creator":"dernst","checksum":"7c6f76ab17393d650825cc240edc84b3","file_name":"2022_CommBiology_Glover.pdf","content_type":"application/pdf","relation":"main_file","file_id":"11342"}],"status":"public","file_date_updated":"2022-05-02T06:26:26Z","volume":5},{"pmid":1,"quality_controlled":"1","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","citation":{"mla":"Le, Dai, et al. “Active Efflux Leads to Heterogeneous Dissipation of Proton Motive Force by Protonophores in Bacteria.” <i>MBio</i>, vol. 12, no. 4, 676, American Society for Microbiology, 2021, doi:<a href=\"https://doi.org/10.1128/mbio.00676-21\">10.1128/mbio.00676-21</a>.","short":"D. Le, E. Krasnopeeva, F. Sinjab, T. Pilizota, M. Kim, MBio 12 (2021).","chicago":"Le, Dai, Ekaterina Krasnopeeva, Faris Sinjab, Teuta Pilizota, and Minsu Kim. “Active Efflux Leads to Heterogeneous Dissipation of Proton Motive Force by Protonophores in Bacteria.” <i>MBio</i>. American Society for Microbiology, 2021. <a href=\"https://doi.org/10.1128/mbio.00676-21\">https://doi.org/10.1128/mbio.00676-21</a>.","ieee":"D. Le, E. Krasnopeeva, F. Sinjab, T. Pilizota, and M. Kim, “Active efflux leads to heterogeneous dissipation of proton motive force by protonophores in bacteria,” <i>mBio</i>, vol. 12, no. 4. American Society for Microbiology, 2021.","apa":"Le, D., Krasnopeeva, E., Sinjab, F., Pilizota, T., &#38; Kim, M. (2021). Active efflux leads to heterogeneous dissipation of proton motive force by protonophores in bacteria. <i>MBio</i>. American Society for Microbiology. <a href=\"https://doi.org/10.1128/mbio.00676-21\">https://doi.org/10.1128/mbio.00676-21</a>","ama":"Le D, Krasnopeeva E, Sinjab F, Pilizota T, Kim M. Active efflux leads to heterogeneous dissipation of proton motive force by protonophores in bacteria. <i>mBio</i>. 2021;12(4). doi:<a href=\"https://doi.org/10.1128/mbio.00676-21\">10.1128/mbio.00676-21</a>","ista":"Le D, Krasnopeeva E, Sinjab F, Pilizota T, Kim M. 2021. Active efflux leads to heterogeneous dissipation of proton motive force by protonophores in bacteria. mBio. 12(4), 676."},"article_number":"676","issue":"4","has_accepted_license":"1","keyword":["Virology","Microbiology"],"publication_identifier":{"issn":["2150-7511"]},"file_date_updated":"2024-04-10T09:05:49Z","volume":12,"status":"public","file":[{"access_level":"open_access","date_updated":"2024-04-10T09:05:49Z","file_size":1344204,"date_created":"2024-04-10T09:05:49Z","file_name":"2021_mBio_Le.pdf","checksum":"529e3f97ae5c5f5cc743c4fc130c9440","content_type":"application/pdf","creator":"dernst","success":1,"file_id":"15309","relation":"main_file"}],"article_processing_charge":"Yes","_id":"15270","author":[{"last_name":"Le","full_name":"Le, Dai","first_name":"Dai"},{"id":"1F1EE44A-BF83-11EA-B3C1-BB9CC619BF3A","first_name":"Ekaterina","full_name":"Krasnopeeva, Ekaterina","last_name":"Krasnopeeva"},{"first_name":"Faris","last_name":"Sinjab","full_name":"Sinjab, Faris"},{"first_name":"Teuta","full_name":"Pilizota, Teuta","last_name":"Pilizota"},{"first_name":"Minsu","full_name":"Kim, Minsu","last_name":"Kim"}],"publisher":"American Society for Microbiology","date_published":"2021-08-31T00:00:00Z","year":"2021","day":"31","department":[{"_id":"CaGu"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa":1,"intvolume":"        12","month":"08","ddc":["570"],"date_created":"2024-04-03T07:51:57Z","publication":"mBio","doi":"10.1128/mbio.00676-21","external_id":{"pmid":["34253054"]},"title":"Active efflux leads to heterogeneous dissipation of proton motive force by protonophores in bacteria","abstract":[{"text":"Various toxic compounds disrupt bacterial physiology. While bacteria harbor defense mechanisms to mitigate the toxicity, these mechanisms are often coupled to the physiological state of the cells and become ineffective when the physiology is severely disrupted.","lang":"eng"}],"date_updated":"2024-04-10T09:13:59Z","publication_status":"published","language":[{"iso":"eng"}],"oa_version":"Published Version"},{"month":"11","isi":1,"date_created":"2021-11-28T23:01:28Z","publication":"Protein Engineering, Design and Selection","oa":1,"intvolume":"        34","scopus_import":"1","publication_status":"published","date_updated":"2023-08-14T13:01:38Z","language":[{"iso":"eng"}],"oa_version":"Published Version","doi":"10.1093/protein/gzab025","abstract":[{"text":"Erythropoietin enhances oxygen delivery and reduces hypoxia-induced cell death, but its pro-thrombotic activity is problematic for use of erythropoietin in treating hypoxia. We constructed a fusion protein that stimulates red blood cell production and neuroprotection without triggering platelet production, a marker for thrombosis. The protein consists of an anti-glycophorin A nanobody and an erythropoietin mutant (L108A). The mutation reduces activation of erythropoietin receptor homodimers that induce erythropoiesis and thrombosis, but maintains the tissue-protective signaling. The binding of the nanobody element to glycophorin A rescues homodimeric erythropoietin receptor activation on red blood cell precursors. In a cell proliferation assay, the fusion protein is active at 10−14 M, allowing an estimate of the number of receptor–ligand complexes needed for signaling. This fusion protein stimulates erythroid cell proliferation in vitro and in mice, and shows neuroprotective activity in vitro. Our erythropoietin fusion protein presents a novel molecule for treating hypoxia.","lang":"eng"}],"title":"Rational engineering of an erythropoietin fusion protein to treat hypoxia","external_id":{"pmid":["34725710"],"isi":["000746596900001"]},"article_number":"gzab025","main_file_link":[{"url":"https://doi.org/10.1093/protein/gzab025","open_access":"1"}],"publication_identifier":{"eissn":["1741-0134"],"issn":["1741-0126"]},"quality_controlled":"1","type":"journal_article","pmid":1,"citation":{"mla":"Lee, Jungmin, et al. “Rational Engineering of an Erythropoietin Fusion Protein to Treat Hypoxia.” <i>Protein Engineering, Design and Selection</i>, vol. 34, gzab025, Oxford University Press, 2021, doi:<a href=\"https://doi.org/10.1093/protein/gzab025\">10.1093/protein/gzab025</a>.","ieee":"J. Lee <i>et al.</i>, “Rational engineering of an erythropoietin fusion protein to treat hypoxia,” <i>Protein Engineering, Design and Selection</i>, vol. 34. Oxford University Press, 2021.","apa":"Lee, J., Vernet, A., Gruber, N., Kready, K. M., Burrill, D. R., Way, J. C., &#38; Silver, P. A. (2021). Rational engineering of an erythropoietin fusion protein to treat hypoxia. <i>Protein Engineering, Design and Selection</i>. Oxford University Press. <a href=\"https://doi.org/10.1093/protein/gzab025\">https://doi.org/10.1093/protein/gzab025</a>","chicago":"Lee, Jungmin, Andyna Vernet, Nathalie Gruber, Kasia M. Kready, Devin R. Burrill, Jeffrey C. Way, and Pamela A. Silver. “Rational Engineering of an Erythropoietin Fusion Protein to Treat Hypoxia.” <i>Protein Engineering, Design and Selection</i>. Oxford University Press, 2021. <a href=\"https://doi.org/10.1093/protein/gzab025\">https://doi.org/10.1093/protein/gzab025</a>.","short":"J. Lee, A. Vernet, N. Gruber, K.M. Kready, D.R. Burrill, J.C. Way, P.A. Silver, Protein Engineering, Design and Selection 34 (2021).","ista":"Lee J, Vernet A, Gruber N, Kready KM, Burrill DR, Way JC, Silver PA. 2021. Rational engineering of an erythropoietin fusion protein to treat hypoxia. Protein Engineering, Design and Selection. 34, gzab025.","ama":"Lee J, Vernet A, Gruber N, et al. Rational engineering of an erythropoietin fusion protein to treat hypoxia. <i>Protein Engineering, Design and Selection</i>. 2021;34. doi:<a href=\"https://doi.org/10.1093/protein/gzab025\">10.1093/protein/gzab025</a>"},"article_type":"original","publisher":"Oxford University Press","_id":"10363","article_processing_charge":"No","author":[{"first_name":"Jungmin","last_name":"Lee","full_name":"Lee, Jungmin"},{"first_name":"Andyna","full_name":"Vernet, Andyna","last_name":"Vernet"},{"id":"2C9C8316-AA17-11E9-B5C2-8BC2E5697425","first_name":"Nathalie","last_name":"Gruber","full_name":"Gruber, Nathalie"},{"first_name":"Kasia M.","full_name":"Kready, Kasia M.","last_name":"Kready"},{"last_name":"Burrill","full_name":"Burrill, Devin R.","first_name":"Devin R."},{"last_name":"Way","full_name":"Way, Jeffrey C.","first_name":"Jeffrey C."},{"first_name":"Pamela A.","full_name":"Silver, Pamela A.","last_name":"Silver"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"CaGu"}],"date_published":"2021-11-01T00:00:00Z","year":"2021","day":"01","acknowledgement":"This work was supported by funds from the Wyss Institute for Biologically Inspired Engineering and the Boston Biomedical Innovation Center (Pilot Award 112475; Drive Award U54HL119145). J.L., K.M.K., D.R.B., J.C.W. and P.A.S. were supported by the Harvard Medical School Department of Systems Biology. J.C.W. was further supported by the Harvard Medical School Laboratory of Systems Pharmacology. A.V., D.R.B. and P.A.S. were further supported by the Wyss Institute for Biologically Inspired Engineering. N.G.G. was sponsored by the Army Research Office under Grant Number W911NF-17-2-0092. The views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the Army Research Office or the U.S. Government. The U.S. Government is authorized to reproduce and distribute reprints for Government purposes notwithstanding any copyright notation herein. We sincerely thank Amanda Graveline and the Wyss Institute at Harvard for their scientific support.","status":"public","volume":34},{"oa":1,"intvolume":"        17","month":"01","isi":1,"ddc":["570"],"date_created":"2021-01-31T23:01:21Z","publication":"PLoS Pathogens","doi":"10.1371/journal.ppat.1009172","title":"Mechanisms and therapeutic potential of collateral sensitivity to antibiotics","external_id":{"isi":["000610190400007"],"pmid":["33444399"]},"scopus_import":"1","publication_status":"published","date_updated":"2025-07-10T12:01:33Z","language":[{"iso":"eng"}],"oa_version":"Published Version","quality_controlled":"1","type":"journal_article","pmid":1,"citation":{"short":"R. Römhild, D.I. Andersson, PLoS Pathogens 17 (2021).","chicago":"Römhild, Roderich, and Dan I. Andersson. “Mechanisms and Therapeutic Potential of Collateral Sensitivity to Antibiotics.” <i>PLoS Pathogens</i>. Public Library of Science, 2021. <a href=\"https://doi.org/10.1371/journal.ppat.1009172\">https://doi.org/10.1371/journal.ppat.1009172</a>.","apa":"Römhild, R., &#38; Andersson, D. I. (2021). Mechanisms and therapeutic potential of collateral sensitivity to antibiotics. <i>PLoS Pathogens</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.ppat.1009172\">https://doi.org/10.1371/journal.ppat.1009172</a>","ieee":"R. Römhild and D. I. Andersson, “Mechanisms and therapeutic potential of collateral sensitivity to antibiotics,” <i>PLoS Pathogens</i>, vol. 17, no. 1. Public Library of Science, 2021.","ista":"Römhild R, Andersson DI. 2021. Mechanisms and therapeutic potential of collateral sensitivity to antibiotics. PLoS Pathogens. 17(1), e1009172.","ama":"Römhild R, Andersson DI. Mechanisms and therapeutic potential of collateral sensitivity to antibiotics. <i>PLoS Pathogens</i>. 2021;17(1). doi:<a href=\"https://doi.org/10.1371/journal.ppat.1009172\">10.1371/journal.ppat.1009172</a>","mla":"Römhild, Roderich, and Dan I. Andersson. “Mechanisms and Therapeutic Potential of Collateral Sensitivity to Antibiotics.” <i>PLoS Pathogens</i>, vol. 17, no. 1, e1009172, Public Library of Science, 2021, doi:<a href=\"https://doi.org/10.1371/journal.ppat.1009172\">10.1371/journal.ppat.1009172</a>."},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","article_number":"e1009172","issue":"1","has_accepted_license":"1","publication_identifier":{"issn":["1553-7366"],"eissn":["1553-7374"]},"acknowledgement":"Our work was supported by the Swedish Research Council (grant 2017-01527) to DIA","status":"public","file":[{"date_created":"2021-02-03T12:13:03Z","file_size":570066,"date_updated":"2021-02-03T12:13:03Z","access_level":"open_access","relation":"main_file","file_id":"9070","creator":"dernst","success":1,"checksum":"d745d7f8fcbb9b95fea16a36f94dee31","file_name":"2021_PlosPathogens_Roemhild.pdf","content_type":"application/pdf"}],"file_date_updated":"2021-02-03T12:13:03Z","volume":17,"publisher":"Public Library of Science","_id":"9046","author":[{"last_name":"Römhild","full_name":"Römhild, Roderich","orcid":"0000-0001-9480-5261","id":"68E56E44-62B0-11EA-B963-444F3DDC885E","first_name":"Roderich"},{"last_name":"Andersson","full_name":"Andersson, Dan I.","first_name":"Dan I."}],"article_processing_charge":"No","department":[{"_id":"CaGu"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_published":"2021-01-14T00:00:00Z","day":"14","year":"2021"},{"quality_controlled":"1","project":[{"grant_number":"628377","call_identifier":"FP7","_id":"2517526A-B435-11E9-9278-68D0E5697425","name":"The Systems Biology of Transcriptional Read-Through in Bacteria: from Synthetic Networks to Genomic Studies"},{"call_identifier":"FWF","name":"Cybergenetic circuits to test composability of gene networks","_id":"268BFA92-B435-11E9-9278-68D0E5697425","grant_number":"I03901"}],"type":"journal_article","pmid":1,"citation":{"ista":"Nagy-Staron AA, Tomasek K, Caruso Carter C, Sonnleitner E, Kavcic B, Paixão T, Guet CC. 2021. Local genetic context shapes the function of a gene regulatory network. eLife. 10, e65993.","ama":"Nagy-Staron AA, Tomasek K, Caruso Carter C, et al. Local genetic context shapes the function of a gene regulatory network. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/elife.65993\">10.7554/elife.65993</a>","ieee":"A. A. Nagy-Staron <i>et al.</i>, “Local genetic context shapes the function of a gene regulatory network,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.","apa":"Nagy-Staron, A. A., Tomasek, K., Caruso Carter, C., Sonnleitner, E., Kavcic, B., Paixão, T., &#38; Guet, C. C. (2021). Local genetic context shapes the function of a gene regulatory network. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.65993\">https://doi.org/10.7554/elife.65993</a>","chicago":"Nagy-Staron, Anna A, Kathrin Tomasek, Caroline Caruso Carter, Elisabeth Sonnleitner, Bor Kavcic, Tiago Paixão, and Calin C Guet. “Local Genetic Context Shapes the Function of a Gene Regulatory Network.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/elife.65993\">https://doi.org/10.7554/elife.65993</a>.","short":"A.A. Nagy-Staron, K. Tomasek, C. Caruso Carter, E. Sonnleitner, B. Kavcic, T. Paixão, C.C. Guet, ELife 10 (2021).","mla":"Nagy-Staron, Anna A., et al. “Local Genetic Context Shapes the Function of a Gene Regulatory Network.” <i>ELife</i>, vol. 10, e65993, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/elife.65993\">10.7554/elife.65993</a>."},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","article_number":"e65993","related_material":{"record":[{"id":"8951","status":"public","relation":"research_data"}]},"has_accepted_license":"1","keyword":["Genetics and Molecular Biology"],"publication_identifier":{"issn":["2050-084X"]},"acknowledgement":"We thank J Bollback, L Hurst, M Lagator, C Nizak, O Rivoire, M Savageau, G Tkacik, and B Vicozo\r\nfor helpful discussions; A Dolinar and A Greshnova for technical assistance; T Bollenbach for supplying the strain JW0336; C Rusnac, and members of the Guet lab for comments. The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement n˚\r\n628377 (ANS) and an Austrian Science Fund (FWF) grant n˚ I 3901-B32 (CCG).","ec_funded":1,"status":"public","file":[{"file_id":"9284","relation":"main_file","content_type":"application/pdf","file_name":"elife-65993-v2.pdf","checksum":"3c2f44058c2dd45a5a1027f09d263f8e","creator":"bkavcic","success":1,"date_created":"2021-03-23T10:12:58Z","file_size":1390469,"access_level":"open_access","date_updated":"2021-03-23T10:12:58Z"}],"file_date_updated":"2021-03-23T10:12:58Z","volume":10,"publisher":"eLife Sciences Publications","_id":"9283","author":[{"first_name":"Anna A","id":"3ABC5BA6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1391-8377","full_name":"Nagy-Staron, Anna A","last_name":"Nagy-Staron"},{"orcid":"0000-0003-3768-877X","first_name":"Kathrin","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","last_name":"Tomasek","full_name":"Tomasek, Kathrin"},{"full_name":"Caruso Carter, Caroline","last_name":"Caruso Carter","first_name":"Caroline"},{"first_name":"Elisabeth","full_name":"Sonnleitner, Elisabeth","last_name":"Sonnleitner"},{"last_name":"Kavcic","full_name":"Kavcic, Bor","orcid":"0000-0001-6041-254X","first_name":"Bor","id":"350F91D2-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Paixão, Tiago","last_name":"Paixão","first_name":"Tiago"},{"full_name":"Guet, Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","orcid":"0000-0001-6220-2052"}],"article_processing_charge":"Yes","department":[{"_id":"GaTk"},{"_id":"CaGu"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_published":"2021-03-08T00:00:00Z","year":"2021","day":"08","oa":1,"intvolume":"        10","month":"03","ddc":["570"],"isi":1,"corr_author":"1","date_created":"2021-03-23T10:11:46Z","publication":"eLife","doi":"10.7554/elife.65993","abstract":[{"text":"Gene expression levels are influenced by multiple coexisting molecular mechanisms. Some of these interactions such as those of transcription factors and promoters have been studied extensively. However, predicting phenotypes of gene regulatory networks (GRNs) remains a major challenge. Here, we use a well-defined synthetic GRN to study in Escherichia coli how network phenotypes depend on local genetic context, i.e. the genetic neighborhood of a transcription factor and its relative position. We show that one GRN with fixed topology can display not only quantitatively but also qualitatively different phenotypes, depending solely on the local genetic context of its components. Transcriptional read-through is the main molecular mechanism that places one transcriptional unit (TU) within two separate regulons without the need for complex regulatory sequences. We propose that relative order of individual TUs, with its potential for combinatorial complexity, plays an important role in shaping phenotypes of GRNs.","lang":"eng"}],"title":"Local genetic context shapes the function of a gene regulatory network","external_id":{"pmid":["33683203"],"isi":["000631050900001"]},"scopus_import":"1","publication_status":"published","date_updated":"2025-06-12T06:36:17Z","language":[{"iso":"eng"}],"oa_version":"Published Version"},{"scopus_import":"1","publication_status":"published","date_updated":"2025-04-15T06:25:56Z","oa_version":"Published Version","language":[{"iso":"eng"}],"doi":"10.1016/j.tcs.2021.05.023","abstract":[{"text":"Gene expression is regulated by the set of transcription factors (TFs) that bind to the promoter. The ensuing regulating function is often represented as a combinational logic circuit, where output (gene expression) is determined by current input values (promoter bound TFs) only. However, the simultaneous arrival of TFs is a strong assumption, since transcription and translation of genes introduce intrinsic time delays and there is no global synchronisation among the arrival times of different molecular species at their targets. We present an experimentally implementable genetic circuit with two inputs and one output, which in the presence of small delays in input arrival, exhibits qualitatively distinct population-level phenotypes, over timescales that are longer than typical cell doubling times. From a dynamical systems point of view, these phenotypes represent long-lived transients: although they converge to the same value eventually, they do so after a very long time span. The key feature of this toy model genetic circuit is that, despite having only two inputs and one output, it is regulated by twenty-three distinct DNA-TF configurations, two of which are more stable than others (DNA looped states), one promoting and another blocking the expression of the output gene. Small delays in input arrival time result in a majority of cells in the population quickly reaching the stable state associated with the first input, while exiting of this stable state occurs at a slow timescale. In order to mechanistically model the behaviour of this genetic circuit, we used a rule-based modelling language, and implemented a grid-search to find parameter combinations giving rise to long-lived transients. Our analysis shows that in the absence of feedback, there exist path-dependent gene regulatory mechanisms based on the long timescale of transients. The behaviour of this toy model circuit suggests that gene regulatory networks can exploit event timing to create phenotypes, and it opens the possibility that they could use event timing to memorise events, without regulatory feedback. The model reveals the importance of (i) mechanistically modelling the transitions between the different DNA-TF states, and (ii) employing transient analysis thereof.","lang":"eng"}],"title":"Long lived transients in gene regulation","external_id":{"isi":["000710180500002"]},"isi":1,"ddc":["004"],"month":"06","corr_author":"1","page":"1-16","publication":"Theoretical Computer Science","date_created":"2021-07-11T22:01:18Z","oa":1,"intvolume":"       893","publisher":"Elsevier","_id":"9647","article_processing_charge":"No","author":[{"first_name":"Tatjana","last_name":"Petrov","full_name":"Petrov, Tatjana"},{"first_name":"Claudia","id":"46613666-F248-11E8-B48F-1D18A9856A87","full_name":"Igler, Claudia","last_name":"Igler"},{"full_name":"Sezgin, Ali","last_name":"Sezgin","id":"4C7638DA-F248-11E8-B48F-1D18A9856A87","first_name":"Ali"},{"orcid":"0000-0002-2985-7724","id":"40876CD8-F248-11E8-B48F-1D18A9856A87","first_name":"Thomas A","last_name":"Henzinger","full_name":"Henzinger, Thomas A"},{"orcid":"0000-0001-6220-2052","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","full_name":"Guet, Calin C"}],"department":[{"_id":"ToHe"},{"_id":"CaGu"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","year":"2021","day":"04","date_published":"2021-06-04T00:00:00Z","acknowledgement":"Tatjana Petrov’s research was supported in part by SNSF Advanced Postdoctoral Mobility Fellowship grant number P300P2 161067, the Ministry of Science, Research and the Arts of the state of Baden-Wurttemberg, and the DFG Centre of Excellence 2117 ‘Centre for the Advanced Study of Collective Behaviour’ (ID: 422037984). Claudia Igler is the recipient of a DOC Fellowship of the Austrian Academy of Sciences. Thomas A. Henzinger’s research was supported in part by the Austrian Science Fund (FWF) under grant Z211-N23 (Wittgenstein Award).","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","file":[{"access_level":"open_access","date_updated":"2022-05-12T12:13:27Z","date_created":"2022-05-12T12:13:27Z","file_size":2566504,"checksum":"d3aef34cfb13e53bba4cf44d01680793","content_type":"application/pdf","file_name":"2021_TheoreticalComputerScience_Petrov.pdf","creator":"dernst","success":1,"file_id":"11364","relation":"main_file"}],"status":"public","volume":893,"file_date_updated":"2022-05-12T12:13:27Z","publication_identifier":{"issn":["0304-3975"]},"has_accepted_license":"1","type":"journal_article","quality_controlled":"1","project":[{"call_identifier":"FWF","name":"Formal methods for the design and analysis of complex systems","_id":"25F42A32-B435-11E9-9278-68D0E5697425","grant_number":"Z211"}],"citation":{"ista":"Petrov T, Igler C, Sezgin A, Henzinger TA, Guet CC. 2021. Long lived transients in gene regulation. Theoretical Computer Science. 893, 1–16.","ama":"Petrov T, Igler C, Sezgin A, Henzinger TA, Guet CC. Long lived transients in gene regulation. <i>Theoretical Computer Science</i>. 2021;893:1-16. doi:<a href=\"https://doi.org/10.1016/j.tcs.2021.05.023\">10.1016/j.tcs.2021.05.023</a>","apa":"Petrov, T., Igler, C., Sezgin, A., Henzinger, T. A., &#38; Guet, C. C. (2021). Long lived transients in gene regulation. <i>Theoretical Computer Science</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.tcs.2021.05.023\">https://doi.org/10.1016/j.tcs.2021.05.023</a>","ieee":"T. Petrov, C. Igler, A. Sezgin, T. A. Henzinger, and C. C. Guet, “Long lived transients in gene regulation,” <i>Theoretical Computer Science</i>, vol. 893. Elsevier, pp. 1–16, 2021.","chicago":"Petrov, Tatjana, Claudia Igler, Ali Sezgin, Thomas A Henzinger, and Calin C Guet. “Long Lived Transients in Gene Regulation.” <i>Theoretical Computer Science</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.tcs.2021.05.023\">https://doi.org/10.1016/j.tcs.2021.05.023</a>.","short":"T. Petrov, C. Igler, A. Sezgin, T.A. Henzinger, C.C. Guet, Theoretical Computer Science 893 (2021) 1–16.","mla":"Petrov, Tatjana, et al. “Long Lived Transients in Gene Regulation.” <i>Theoretical Computer Science</i>, vol. 893, Elsevier, 2021, pp. 1–16, doi:<a href=\"https://doi.org/10.1016/j.tcs.2021.05.023\">10.1016/j.tcs.2021.05.023</a>."},"tmp":{"short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","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"},"article_type":"original"},{"scopus_import":"1","date_updated":"2023-08-11T10:26:29Z","publication_status":"published","oa_version":"Published Version","language":[{"iso":"eng"}],"doi":"10.7554/elife.68876","abstract":[{"lang":"eng","text":"Evolutionary adaptation is a major source of antibiotic resistance in bacterial pathogens. Evolution-informed therapy aims to constrain resistance by accounting for bacterial evolvability. Sequential treatments with antibiotics that target different bacterial processes were previously shown to limit adaptation through genetic resistance trade-offs and negative hysteresis. Treatment with homogeneous sets of antibiotics is generally viewed to be disadvantageous, as it should rapidly lead to cross-resistance. We here challenged this assumption by determining the evolutionary response of Pseudomonas aeruginosa to experimental sequential treatments involving both heterogenous and homogeneous antibiotic sets. To our surprise, we found that fast switching between only β-lactam antibiotics resulted in increased extinction of bacterial populations. We demonstrate that extinction is favored by low rates of spontaneous resistance emergence and low levels of spontaneous cross-resistance among the antibiotics in sequence. The uncovered principles may help to guide the optimized use of available antibiotics in highly potent, evolution-informed treatment designs."}],"title":"High potency of sequential therapy with only beta-lactam antibiotics","external_id":{"pmid":["34318749"],"isi":["000692027800001"]},"isi":1,"month":"07","publication":"eLife","date_created":"2021-07-28T13:36:57Z","oa":1,"intvolume":"        10","publisher":"eLife Sciences Publications","author":[{"last_name":"Batra","full_name":"Batra, Aditi","first_name":"Aditi"},{"orcid":"0000-0001-9480-5261","id":"68E56E44-62B0-11EA-B963-444F3DDC885E","first_name":"Roderich","last_name":"Römhild","full_name":"Römhild, Roderich"},{"last_name":"Rousseau","full_name":"Rousseau, Emilie","first_name":"Emilie"},{"first_name":"Sören","last_name":"Franzenburg","full_name":"Franzenburg, Sören"},{"last_name":"Niemann","full_name":"Niemann, Stefan","first_name":"Stefan"},{"full_name":"Schulenburg, Hinrich","last_name":"Schulenburg","first_name":"Hinrich"}],"_id":"9746","article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"CaGu"}],"day":"28","year":"2021","date_published":"2021-07-28T00:00:00Z","acknowledgement":"We would like to thank Leif Tueffers and João Botelho for discussions and suggestions as well as Kira Haas and Julia Bunk for technical support. We acknowledge financial support from the German Science Foundation (grant SCHU 1415/12-2 to HS, and funding under Germany’s Excellence Strategy EXC 2167–390884018 as well as the Research Training Group 2501 TransEvo to HS and SN), the Max Planck Society (IMPRS scholarship to AB; Max-Planck fellowship to HS), and the Leibniz Science Campus Evolutionary Medicine of the Lung (EvoLUNG, to HS and SN). This work was further supported by the German Science Foundation Research Infrastructure NGS_CC (project 407495230) as part of the Next Generation Sequencing Competence Network (project 423957469). NGS analyses were carried out at the Competence Centre for Genomic Analysis Kiel (CCGA Kiel).","status":"public","volume":10,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.7554/eLife.68876"}],"article_number":"e68876","publication_identifier":{"eissn":["2050-084X"]},"type":"journal_article","quality_controlled":"1","pmid":1,"citation":{"mla":"Batra, Aditi, et al. “High Potency of Sequential Therapy with Only Beta-Lactam Antibiotics.” <i>ELife</i>, vol. 10, e68876, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/elife.68876\">10.7554/elife.68876</a>.","ista":"Batra A, Römhild R, Rousseau E, Franzenburg S, Niemann S, Schulenburg H. 2021. High potency of sequential therapy with only beta-lactam antibiotics. eLife. 10, e68876.","ama":"Batra A, Römhild R, Rousseau E, Franzenburg S, Niemann S, Schulenburg H. High potency of sequential therapy with only beta-lactam antibiotics. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/elife.68876\">10.7554/elife.68876</a>","ieee":"A. Batra, R. Römhild, E. Rousseau, S. Franzenburg, S. Niemann, and H. Schulenburg, “High potency of sequential therapy with only beta-lactam antibiotics,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.","apa":"Batra, A., Römhild, R., Rousseau, E., Franzenburg, S., Niemann, S., &#38; Schulenburg, H. (2021). High potency of sequential therapy with only beta-lactam antibiotics. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.68876\">https://doi.org/10.7554/elife.68876</a>","short":"A. Batra, R. Römhild, E. Rousseau, S. Franzenburg, S. Niemann, H. Schulenburg, ELife 10 (2021).","chicago":"Batra, Aditi, Roderich Römhild, Emilie Rousseau, Sören Franzenburg, Stefan Niemann, and Hinrich Schulenburg. “High Potency of Sequential Therapy with Only Beta-Lactam Antibiotics.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/elife.68876\">https://doi.org/10.7554/elife.68876</a>."},"article_type":"original"},{"department":[{"_id":"MiSi"},{"_id":"GaTk"},{"_id":"Bio"},{"_id":"CaGu"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","day":"04","year":"2021","date_published":"2021-08-04T00:00:00Z","publisher":"American Chemical Society","author":[{"full_name":"Zisis, Themistoklis","last_name":"Zisis","first_name":"Themistoklis"},{"last_name":"Schwarz","full_name":"Schwarz, Jan","first_name":"Jan","id":"346C1EC6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Miriam","last_name":"Balles","full_name":"Balles, Miriam"},{"last_name":"Kretschmer","full_name":"Kretschmer, Maibritt","first_name":"Maibritt"},{"last_name":"Nemethova","full_name":"Nemethova, Maria","first_name":"Maria","id":"34E27F1C-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-0876-3187","id":"3464AE84-F248-11E8-B48F-1D18A9856A87","first_name":"Remy P","last_name":"Chait","full_name":"Chait, Remy P"},{"first_name":"Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9843-3522","full_name":"Hauschild, Robert","last_name":"Hauschild"},{"full_name":"Lange, Janina","last_name":"Lange","first_name":"Janina"},{"full_name":"Guet, Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","orcid":"0000-0001-6220-2052"},{"first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4561-241X","full_name":"Sixt, Michael K","last_name":"Sixt"},{"full_name":"Zahler, Stefan","last_name":"Zahler","first_name":"Stefan"}],"_id":"9822","article_processing_charge":"Yes (in subscription journal)","file":[{"file_id":"9833","relation":"main_file","checksum":"b043a91d9f9200e467b970b692687ed3","file_name":"2021_ACSAppliedMaterialsAndInterfaces_Zisis.pdf","content_type":"application/pdf","creator":"asandaue","success":1,"file_size":7123293,"date_created":"2021-08-09T09:44:03Z","access_level":"open_access","date_updated":"2021-08-09T09:44:03Z"}],"ec_funded":1,"status":"public","volume":13,"file_date_updated":"2021-08-09T09:44:03Z","acknowledgement":"We would like to thank Charlott Leu for the production of our chromium wafers, Louise Ritter for her contribution of the IF stainings in Figure 4, Shokoufeh Teymouri for her help with the Bioinert coated slides, and finally Prof. Dr. Joachim Rädler for his valuable scientific guidance.","publication_identifier":{"eissn":["1944-8252"],"issn":["1944-8244"]},"has_accepted_license":"1","issue":"30","citation":{"ieee":"T. Zisis <i>et al.</i>, “Sequential and switchable patterning for studying cellular processes under spatiotemporal control,” <i>ACS Applied Materials and Interfaces</i>, vol. 13, no. 30. American Chemical Society, pp. 35545–35560, 2021.","apa":"Zisis, T., Schwarz, J., Balles, M., Kretschmer, M., Nemethova, M., Chait, R. P., … Zahler, S. (2021). Sequential and switchable patterning for studying cellular processes under spatiotemporal control. <i>ACS Applied Materials and Interfaces</i>. American Chemical Society. <a href=\"https://doi.org/10.1021/acsami.1c09850\">https://doi.org/10.1021/acsami.1c09850</a>","short":"T. Zisis, J. Schwarz, M. Balles, M. Kretschmer, M. Nemethova, R.P. Chait, R. Hauschild, J. Lange, C.C. Guet, M.K. Sixt, S. Zahler, ACS Applied Materials and Interfaces 13 (2021) 35545–35560.","chicago":"Zisis, Themistoklis, Jan Schwarz, Miriam Balles, Maibritt Kretschmer, Maria Nemethova, Remy P Chait, Robert Hauschild, et al. “Sequential and Switchable Patterning for Studying Cellular Processes under Spatiotemporal Control.” <i>ACS Applied Materials and Interfaces</i>. American Chemical Society, 2021. <a href=\"https://doi.org/10.1021/acsami.1c09850\">https://doi.org/10.1021/acsami.1c09850</a>.","ama":"Zisis T, Schwarz J, Balles M, et al. Sequential and switchable patterning for studying cellular processes under spatiotemporal control. <i>ACS Applied Materials and Interfaces</i>. 2021;13(30):35545–35560. doi:<a href=\"https://doi.org/10.1021/acsami.1c09850\">10.1021/acsami.1c09850</a>","ista":"Zisis T, Schwarz J, Balles M, Kretschmer M, Nemethova M, Chait RP, Hauschild R, Lange J, Guet CC, Sixt MK, Zahler S. 2021. Sequential and switchable patterning for studying cellular processes under spatiotemporal control. ACS Applied Materials and Interfaces. 13(30), 35545–35560.","mla":"Zisis, Themistoklis, et al. “Sequential and Switchable Patterning for Studying Cellular Processes under Spatiotemporal Control.” <i>ACS Applied Materials and Interfaces</i>, vol. 13, no. 30, American Chemical Society, 2021, pp. 35545–35560, doi:<a href=\"https://doi.org/10.1021/acsami.1c09850\">10.1021/acsami.1c09850</a>."},"article_type":"original","tmp":{"short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","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"},"type":"journal_article","quality_controlled":"1","project":[{"grant_number":"724373","call_identifier":"H2020","name":"Cellular Navigation Along Spatial Gradients","_id":"25FE9508-B435-11E9-9278-68D0E5697425"}],"pmid":1,"oa_version":"Published Version","language":[{"iso":"eng"}],"scopus_import":"1","publication_status":"published","date_updated":"2025-07-10T12:02:02Z","title":"Sequential and switchable patterning for studying cellular processes under spatiotemporal control","abstract":[{"text":"Attachment of adhesive molecules on cell culture surfaces to restrict cell adhesion to defined areas and shapes has been vital for the progress of in vitro research. In currently existing patterning methods, a combination of pattern properties such as stability, precision, specificity, high-throughput outcome, and spatiotemporal control is highly desirable but challenging to achieve. Here, we introduce a versatile and high-throughput covalent photoimmobilization technique, comprising a light-dose-dependent patterning step and a subsequent functionalization of the pattern via click chemistry. This two-step process is feasible on arbitrary surfaces and allows for generation of sustainable patterns and gradients. The method is validated in different biological systems by patterning adhesive ligands on cell-repellent surfaces, thereby constraining the growth and migration of cells to the designated areas. We then implement a sequential photopatterning approach by adding a second switchable patterning step, allowing for spatiotemporal control over two distinct surface patterns. As a proof of concept, we reconstruct the dynamics of the tip/stalk cell switch during angiogenesis. Our results show that the spatiotemporal control provided by our “sequential photopatterning” system is essential for mimicking dynamic biological processes and that our innovative approach has great potential for further applications in cell science.","lang":"eng"}],"external_id":{"isi":["000683741400026"],"pmid":["34283577"]},"doi":"10.1021/acsami.1c09850","publication":"ACS Applied Materials and Interfaces","page":"35545–35560","date_created":"2021-08-08T22:01:28Z","isi":1,"ddc":["620","570"],"month":"08","corr_author":"1","intvolume":"        13","oa":1},{"department":[{"_id":"MiSi"},{"_id":"CaGu"},{"_id":"GradSch"}],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","date_published":"2021-11-18T00:00:00Z","day":"18","year":"2021","alternative_title":["ISTA Thesis"],"publisher":"Institute of Science and Technology Austria","_id":"10307","author":[{"last_name":"Tomasek","full_name":"Tomasek, Kathrin","orcid":"0000-0003-3768-877X","first_name":"Kathrin","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"No","status":"public","file":[{"creator":"ktomasek","file_name":"ThesisTomasekKathrin.pdf","checksum":"b39c9e0ef18d0484d537a67551effd02","content_type":"application/pdf","relation":"main_file","embargo":"2022-11-18","file_id":"10308","date_updated":"2022-12-20T23:30:05Z","access_level":"open_access","date_created":"2021-11-18T15:07:31Z","file_size":13266088},{"checksum":"c0c440ee9e5ef1102a518a4f9f023e7c","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_name":"ThesisTomasekKathrin.docx","creator":"ktomasek","file_id":"10309","embargo_to":"open_access","relation":"source_file","access_level":"closed","date_updated":"2022-12-20T23:30:05Z","file_size":7539509,"date_created":"2021-11-18T15:07:46Z"}],"file_date_updated":"2022-12-20T23:30:05Z","has_accepted_license":"1","publication_identifier":{"issn":["2663-337X"]},"related_material":{"record":[{"id":"10316","status":"public","relation":"part_of_dissertation"}]},"citation":{"mla":"Tomasek, Kathrin. <i>Pathogenic Escherichia Coli Hijack the Host Immune Response</i>. Institute of Science and Technology Austria, 2021, doi:<a href=\"https://doi.org/10.15479/at:ista:10307\">10.15479/at:ista:10307</a>.","ista":"Tomasek K. 2021. Pathogenic Escherichia coli hijack the host immune response. Institute of Science and Technology Austria.","ama":"Tomasek K. Pathogenic Escherichia coli hijack the host immune response. 2021. doi:<a href=\"https://doi.org/10.15479/at:ista:10307\">10.15479/at:ista:10307</a>","ieee":"K. Tomasek, “Pathogenic Escherichia coli hijack the host immune response,” Institute of Science and Technology Austria, 2021.","apa":"Tomasek, K. (2021). <i>Pathogenic Escherichia coli hijack the host immune response</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:10307\">https://doi.org/10.15479/at:ista:10307</a>","short":"K. Tomasek, Pathogenic Escherichia Coli Hijack the Host Immune Response, Institute of Science and Technology Austria, 2021.","chicago":"Tomasek, Kathrin. “Pathogenic Escherichia Coli Hijack the Host Immune Response.” Institute of Science and Technology Austria, 2021. <a href=\"https://doi.org/10.15479/at:ista:10307\">https://doi.org/10.15479/at:ista:10307</a>."},"type":"dissertation","language":[{"iso":"eng"}],"oa_version":"Published Version","publication_status":"published","date_updated":"2026-04-08T07:14:01Z","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"abstract":[{"text":"Bacteria-host interactions represent a continuous trade-off between benefit and risk. Thus, the host immune response is faced with a non-trivial problem – accommodate beneficial commensals and remove harmful pathogens. This is especially difficult as molecular patterns, such as lipopolysaccharide or specific surface organelles such as pili, are conserved in both, commensal and pathogenic bacteria. Type 1 pili, tightly regulated by phase variation, are considered an important virulence factor of pathogenic bacteria as they facilitate invasion into host cells. While invasion represents a de facto passive mechanism for pathogens to escape the host immune response, we demonstrate a fundamental role of type 1 pili as active modulators of the innate and adaptive immune response.","lang":"eng"}],"title":"Pathogenic Escherichia coli hijack the host immune response","degree_awarded":"PhD","OA_place":"publisher","doi":"10.15479/at:ista:10307","date_created":"2021-11-18T15:05:06Z","page":"73","month":"11","ddc":["570"],"supervisor":[{"orcid":"0000-0002-4561-241X","first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","full_name":"Sixt, Michael K"},{"first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","last_name":"Guet"}],"corr_author":"1","oa":1},{"article_processing_charge":"No","_id":"10316","date_updated":"2026-06-05T22:33:36Z","author":[{"id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","first_name":"Kathrin","orcid":"0000-0003-3768-877X","full_name":"Tomasek, Kathrin","last_name":"Tomasek"},{"first_name":"Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1073-744X","full_name":"Leithner, Alexander F","last_name":"Leithner"},{"last_name":"Glatzová","full_name":"Glatzová, Ivana","id":"727b3c7d-4939-11ec-89b3-b9b0750ab74d","first_name":"Ivana"},{"full_name":"Lukesch, Michael S.","last_name":"Lukesch","first_name":"Michael S."},{"last_name":"Guet","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Sixt","full_name":"Sixt, Michael K","orcid":"0000-0002-4561-241X","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K"}],"publication_status":"draft","publisher":"Cold Spring Harbor Laboratory","day":"18","year":"2021","oa_version":"Preprint","language":[{"iso":"eng"}],"date_published":"2021-10-18T00:00:00Z","department":[{"_id":"CaGu"},{"_id":"MiSi"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","doi":"10.1101/2021.10.18.464770","acknowledgement":"We thank Ulrich Dobrindt for providing UPEC strain CFT073, Vlad Gavra and Maximilian Götz, Bor Kavčič, Jonna Alanko and Eva Kiermaier for help with experiments and Robert Hauschild, Julian Stopp and Saren Tasciyan for help with data analysis. We thank the IST Austria Scientific Service Units, especially the Bioimaging facility, the Preclinical facility and the Electron microscopy facility for technical support, Jakob Wallner and all members of the Guet and Sixt lab for fruitful discussions and Daria Siekhaus for critically reading the manuscript. This work was supported by grants from the Austrian Research Promotion Agency (FEMtech 868984) to I.G., the European Research Council (CoG 724373) and the Austrian Science Fund (FWF P29911) to M.S.","abstract":[{"text":"A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on dendritic cells as a previously undescribed binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of pathogenic bacteria to CD14 lead to reduced dendritic cell migration and blunted expression of co-stimulatory molecules, both rate-limiting factors of T cell activation. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease.","lang":"eng"}],"title":"Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14","status":"public","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"ec_funded":1,"corr_author":"1","related_material":{"record":[{"id":"11843","relation":"later_version","status":"public"},{"status":"public","relation":"dissertation_contains","id":"10307"}]},"main_file_link":[{"url":"https://www.biorxiv.org/content/10.1101/2021.10.18.464770v1","open_access":"1"}],"month":"10","publication":"bioRxiv","date_created":"2021-11-19T12:24:16Z","type":"preprint","oa":1,"project":[{"name":"Cellular Navigation Along Spatial Gradients","_id":"25FE9508-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"724373"},{"call_identifier":"FWF","_id":"26018E70-B435-11E9-9278-68D0E5697425","name":"Mechanical adaptation of lamellipodial actin","grant_number":"P29911"}],"citation":{"mla":"Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href=\"https://doi.org/10.1101/2021.10.18.464770\">10.1101/2021.10.18.464770</a>.","chicago":"Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch, Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2021.10.18.464770\">https://doi.org/10.1101/2021.10.18.464770</a>.","short":"K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt, BioRxiv (n.d.).","ieee":"K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M. K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory.","apa":"Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., &#38; Sixt, M. K. (n.d.). Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2021.10.18.464770\">https://doi.org/10.1101/2021.10.18.464770</a>","ama":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2021.10.18.464770\">10.1101/2021.10.18.464770</a>","ista":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. bioRxiv, <a href=\"https://doi.org/10.1101/2021.10.18.464770\">10.1101/2021.10.18.464770</a>."}},{"corr_author":"1","related_material":{"record":[{"id":"9283","status":"public","relation":"used_in_publication"}]},"ddc":["570"],"month":"12","date_created":"2020-12-20T10:00:26Z","keyword":["Gene regulatory networks","Gene expression","Escherichia coli","Synthetic Biology"],"has_accepted_license":"1","oa":1,"type":"research_data","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"citation":{"ieee":"A. A. Nagy-Staron, “Sequences of gene regulatory network permutations for the article ‘Local genetic context shapes the function of a gene regulatory network.’” Institute of Science and Technology Austria, 2020.","apa":"Nagy-Staron, A. A. (2020). Sequences of gene regulatory network permutations for the article “Local genetic context shapes the function of a gene regulatory network.” Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:8951\">https://doi.org/10.15479/AT:ISTA:8951</a>","short":"A.A. Nagy-Staron, (2020).","chicago":"Nagy-Staron, Anna A. “Sequences of Gene Regulatory Network Permutations for the Article ‘Local Genetic Context Shapes the Function of a Gene Regulatory Network.’” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:8951\">https://doi.org/10.15479/AT:ISTA:8951</a>.","ama":"Nagy-Staron AA. Sequences of gene regulatory network permutations for the article “Local genetic context shapes the function of a gene regulatory network.” 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8951\">10.15479/AT:ISTA:8951</a>","ista":"Nagy-Staron AA. 2020. Sequences of gene regulatory network permutations for the article ‘Local genetic context shapes the function of a gene regulatory network’, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:8951\">10.15479/AT:ISTA:8951</a>.","mla":"Nagy-Staron, Anna A. <i>Sequences of Gene Regulatory Network Permutations for the Article “Local Genetic Context Shapes the Function of a Gene Regulatory Network.”</i> Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8951\">10.15479/AT:ISTA:8951</a>."},"_id":"8951","date_updated":"2025-06-12T06:36:16Z","article_processing_charge":"No","author":[{"full_name":"Nagy-Staron, Anna A","last_name":"Nagy-Staron","id":"3ABC5BA6-F248-11E8-B48F-1D18A9856A87","first_name":"Anna A","orcid":"0000-0002-1391-8377"}],"publisher":"Institute of Science and Technology Austria","year":"2020","day":"21","oa_version":"Published Version","date_published":"2020-12-21T00:00:00Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"CaGu"}],"doi":"10.15479/AT:ISTA:8951","file_date_updated":"2020-12-20T22:01:44Z","file":[{"access_level":"open_access","date_updated":"2020-12-20T09:52:52Z","date_created":"2020-12-20T09:52:52Z","file_size":523,"file_name":"readme.txt","checksum":"f57862aeee1690c7effd2b1117d40ed1","content_type":"text/plain","creator":"bkavcic","success":1,"file_id":"8952","relation":"main_file"},{"file_size":379228,"date_created":"2020-12-20T22:01:44Z","access_level":"open_access","date_updated":"2020-12-20T22:01:44Z","file_id":"8954","relation":"main_file","file_name":"GRNs Research depository.gb","checksum":"f2c6d5232ec6d551b6993991e8689e9f","content_type":"application/octet-stream","creator":"bkavcic","success":1}],"contributor":[{"first_name":"Anna A","id":"3ABC5BA6-F248-11E8-B48F-1D18A9856A87","contributor_type":"project_member","last_name":"Nagy-Staron"},{"last_name":"Tomasek","contributor_type":"project_member","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","first_name":"Kathrin"},{"last_name":"Caruso Carter","contributor_type":"project_member","first_name":"Caroline"},{"last_name":"Sonnleitner","contributor_type":"project_member","first_name":"Elisabeth"},{"orcid":"0000-0001-6041-254X","contributor_type":"project_member","id":"350F91D2-F248-11E8-B48F-1D18A9856A87","first_name":"Bor","last_name":"Kavcic"},{"first_name":"Tiago","contributor_type":"project_member","last_name":"Paixão"},{"contributor_type":"project_manager","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","last_name":"Guet"}],"abstract":[{"lang":"eng","text":"Gene expression levels are influenced by multiple coexisting molecular mechanisms. Some of these interactions, such as those of transcription factors and promoters have been studied extensively. However, predicting phenotypes of gene regulatory networks remains a major challenge. Here, we use a well-defined synthetic gene regulatory network to study how network phenotypes depend on local genetic context, i.e. the genetic neighborhood of a transcription factor and its relative position. We show that one gene regulatory network with fixed topology can display not only quantitatively but also qualitatively different phenotypes, depending solely on the local genetic context of its components. Our results demonstrate that changes in local genetic context can place a single transcriptional unit within two separate regulons without the need for complex regulatory sequences. We propose that relative order of individual transcriptional units, with its potential for combinatorial complexity, plays an important role in shaping phenotypes of gene regulatory networks."}],"status":"public","title":"Sequences of gene regulatory network permutations for the article \"Local genetic context shapes the function of a gene regulatory network\""},{"type":"research_data","oa":1,"citation":{"mla":"Grah, Rok. <i>Matlab Scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression Regulation</i>. Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7383\">10.15479/AT:ISTA:7383</a>.","chicago":"Grah, Rok. “Matlab Scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression Regulation.” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:7383\">https://doi.org/10.15479/AT:ISTA:7383</a>.","short":"R. Grah, (2020).","ieee":"R. Grah, “Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation.” Institute of Science and Technology Austria, 2020.","apa":"Grah, R. (2020). Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:7383\">https://doi.org/10.15479/AT:ISTA:7383</a>","ista":"Grah R. 2020. Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:7383\">10.15479/AT:ISTA:7383</a>.","ama":"Grah R. Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation. 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7383\">10.15479/AT:ISTA:7383</a>"},"corr_author":"1","related_material":{"record":[{"relation":"used_in_publication","status":"public","id":"7652"}]},"month":"01","date_created":"2020-01-28T10:41:49Z","keyword":["Matlab scripts","analysis of microfluidics","mathematical model"],"has_accepted_license":"1","doi":"10.15479/AT:ISTA:7383","file_date_updated":"2020-07-14T12:47:57Z","status":"public","abstract":[{"lang":"eng","text":"Organisms cope with change by employing transcriptional regulators. However, when faced with rare environments, the evolution of transcriptional regulators and their promoters may be too slow. We ask whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. By real-time monitoring of gene copy number mutations in E. coli, we show that gene duplications and amplifications enable adaptation to fluctuating environments by rapidly generating copy number, and hence expression level, polymorphism. This ‘amplification-mediated gene expression tuning’ occurs on timescales similar to canonical gene regulation and can deal with rapid environmental changes. Mathematical modeling shows that amplifications also tune gene expression in stochastic environments where transcription factor-based schemes are hard to evolve or maintain. The fleeting nature of gene amplifications gives rise to a generic population-level mechanism that relies on genetic heterogeneity to rapidly tune expression of any gene, without leaving any genomic signature."}],"title":"Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level Gene Expression regulation","contributor":[{"contributor_type":"project_leader","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","orcid":"0000-0001-6220-2052","last_name":"Guet"}],"file":[{"date_updated":"2020-07-14T12:47:57Z","access_level":"open_access","date_created":"2020-01-28T10:39:40Z","file_size":73363365,"creator":"rgrah","content_type":"application/zip","file_name":"Scripts.zip","checksum":"9d292cf5207b3829225f44c044cdb3fd","relation":"main_file","file_id":"7384"},{"date_created":"2020-01-28T10:39:30Z","file_size":962,"access_level":"open_access","date_updated":"2020-07-14T12:47:57Z","file_id":"7385","relation":"main_file","file_name":"READ_ME_MAIN.txt","content_type":"text/plain","checksum":"4076ceab32ef588cc233802bab24c1ab","creator":"rgrah"}],"article_processing_charge":"No","_id":"7383","date_updated":"2025-06-12T07:34:12Z","author":[{"first_name":"Rok","id":"483E70DE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2539-3560","full_name":"Grah, Rok","last_name":"Grah"}],"publisher":"Institute of Science and Technology Austria","date_published":"2020-01-28T00:00:00Z","oa_version":"Published Version","day":"28","year":"2020","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"CaGu"},{"_id":"GaTk"}]},{"oa":1,"intvolume":"        16","month":"02","ddc":["000","570"],"isi":1,"date_created":"2020-03-06T07:39:38Z","publication":"PLOS Computational Biology","doi":"10.1371/journal.pcbi.1007642","abstract":[{"text":"Genes differ in the frequency at which they are expressed and in the form of regulation used to control their activity. In particular, positive or negative regulation can lead to activation of a gene in response to an external signal. Previous works proposed that the form of regulation of a gene correlates with its frequency of usage: positive regulation when the gene is frequently expressed and negative regulation when infrequently expressed. Such network design means that, in the absence of their regulators, the genes are found in their least required activity state, hence regulatory intervention is often necessary. Due to the multitude of genes and regulators, spurious binding and unbinding events, called “crosstalk”, could occur. To determine how the form of regulation affects the global crosstalk in the network, we used a mathematical model that includes multiple regulators and multiple target genes. We found that crosstalk depends non-monotonically on the availability of regulators. Our analysis showed that excess use of regulation entailed by the formerly suggested network design caused high crosstalk levels in a large part of the parameter space. We therefore considered the opposite ‘idle’ design, where the default unregulated state of genes is their frequently required activity state. We found, that ‘idle’ design minimized the use of regulation and thus minimized crosstalk. In addition, we estimated global crosstalk of S. cerevisiae using transcription factors binding data. We demonstrated that even partial network data could suffice to estimate its global crosstalk, suggesting its applicability to additional organisms. We found that S. cerevisiae estimated crosstalk is lower than that of a random network, suggesting that natural selection reduces crosstalk. In summary, our study highlights a new type of protein production cost which is typically overlooked: that of regulatory interference caused by the presence of excess regulators in the cell. It demonstrates the importance of whole-network descriptions, which could show effects missed by single-gene models.","lang":"eng"}],"title":"The relation between crosstalk and gene regulation form revisited","external_id":{"pmid":["32097416"],"isi":["000526725200019"]},"scopus_import":"1","publication_status":"published","date_updated":"2026-04-08T07:25:08Z","language":[{"iso":"eng"}],"oa_version":"Published Version","quality_controlled":"1","type":"journal_article","pmid":1,"citation":{"mla":"Grah, Rok, and Tamar Friedlander. “The Relation between Crosstalk and Gene Regulation Form Revisited.” <i>PLOS Computational Biology</i>, vol. 16, no. 2, e1007642, Public Library of Science, 2020, doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1007642\">10.1371/journal.pcbi.1007642</a>.","ista":"Grah R, Friedlander T. 2020. The relation between crosstalk and gene regulation form revisited. PLOS Computational Biology. 16(2), e1007642.","ama":"Grah R, Friedlander T. The relation between crosstalk and gene regulation form revisited. <i>PLOS Computational Biology</i>. 2020;16(2). doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1007642\">10.1371/journal.pcbi.1007642</a>","apa":"Grah, R., &#38; Friedlander, T. (2020). The relation between crosstalk and gene regulation form revisited. <i>PLOS Computational Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pcbi.1007642\">https://doi.org/10.1371/journal.pcbi.1007642</a>","ieee":"R. Grah and T. Friedlander, “The relation between crosstalk and gene regulation form revisited,” <i>PLOS Computational Biology</i>, vol. 16, no. 2. Public Library of Science, 2020.","short":"R. Grah, T. Friedlander, PLOS Computational Biology 16 (2020).","chicago":"Grah, Rok, and Tamar Friedlander. “The Relation between Crosstalk and Gene Regulation Form Revisited.” <i>PLOS Computational Biology</i>. Public Library of Science, 2020. <a href=\"https://doi.org/10.1371/journal.pcbi.1007642\">https://doi.org/10.1371/journal.pcbi.1007642</a>."},"article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_number":"e1007642","issue":"2","related_material":{"record":[{"id":"9716","status":"deleted","relation":"research_data"},{"relation":"research_data","status":"public","id":"9776"},{"id":"9779","relation":"research_data","status":"public"},{"id":"9777","relation":"research_data","status":"public"},{"relation":"dissertation_contains","status":"public","id":"8155"}]},"has_accepted_license":"1","publication_identifier":{"issn":["1553-7358"]},"status":"public","file":[{"file_id":"7579","relation":"main_file","checksum":"5239dd134dc6e1c71fe7b3ce2953da37","content_type":"application/pdf","file_name":"2020_PlosCompBio_Grah.pdf","creator":"dernst","file_size":2209325,"date_created":"2020-03-09T15:12:21Z","access_level":"open_access","date_updated":"2020-07-14T12:48:00Z"}],"volume":16,"file_date_updated":"2020-07-14T12:48:00Z","publisher":"Public Library of Science","_id":"7569","author":[{"last_name":"Grah","full_name":"Grah, Rok","orcid":"0000-0003-2539-3560","id":"483E70DE-F248-11E8-B48F-1D18A9856A87","first_name":"Rok"},{"first_name":"Tamar","last_name":"Friedlander","full_name":"Friedlander, Tamar"}],"article_processing_charge":"No","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"date_published":"2020-02-25T00:00:00Z","day":"25","year":"2020"}]