[{"title":"Effects of mutations in phage restriction sites during escape from restriction–modification","main_file_link":[{"url":"https://doi.org/10.1098/rsbl.2017.0646","open_access":"1"}],"article_type":"original","publisher":"The Royal Society","_id":"561","oa":1,"date_published":"2017-12-01T00:00:00Z","volume":13,"month":"12","language":[{"iso":"eng"}],"related_material":{"record":[{"relation":"research_data","status":"public","id":"9847"},{"relation":"dissertation_contains","id":"202","status":"public"}]},"isi":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","corr_author":"1","publication":"Biology Letters","intvolume":"        13","citation":{"ama":"Pleska M, Guet CC. Effects of mutations in phage restriction sites during escape from restriction–modification. <i>Biology Letters</i>. 2017;13(12). doi:<a href=\"https://doi.org/10.1098/rsbl.2017.0646\">10.1098/rsbl.2017.0646</a>","short":"M. Pleska, C.C. Guet, Biology Letters 13 (2017).","ieee":"M. Pleska and C. C. Guet, “Effects of mutations in phage restriction sites during escape from restriction–modification,” <i>Biology Letters</i>, vol. 13, no. 12. The Royal Society, 2017.","ista":"Pleska M, Guet CC. 2017. Effects of mutations in phage restriction sites during escape from restriction–modification. Biology Letters. 13(12), 20170646.","chicago":"Pleska, Maros, and Calin C Guet. “Effects of Mutations in Phage Restriction Sites during Escape from Restriction–Modification.” <i>Biology Letters</i>. The Royal Society, 2017. <a href=\"https://doi.org/10.1098/rsbl.2017.0646\">https://doi.org/10.1098/rsbl.2017.0646</a>.","mla":"Pleska, Maros, and Calin C. Guet. “Effects of Mutations in Phage Restriction Sites during Escape from Restriction–Modification.” <i>Biology Letters</i>, vol. 13, no. 12, 20170646, The Royal Society, 2017, doi:<a href=\"https://doi.org/10.1098/rsbl.2017.0646\">10.1098/rsbl.2017.0646</a>.","apa":"Pleska, M., &#38; Guet, C. C. (2017). Effects of mutations in phage restriction sites during escape from restriction–modification. <i>Biology Letters</i>. The Royal Society. <a href=\"https://doi.org/10.1098/rsbl.2017.0646\">https://doi.org/10.1098/rsbl.2017.0646</a>"},"date_created":"2018-12-11T11:47:11Z","publication_status":"published","doi":"10.1098/rsbl.2017.0646","article_processing_charge":"No","publication_identifier":{"issn":["1744-9561"]},"oa_version":"Published Version","article_number":"20170646","external_id":{"isi":["000418695400012"],"pmid":["29237814"]},"abstract":[{"lang":"eng","text":"Restriction–modification systems are widespread genetic elements that protect bacteria from bacteriophage infections by recognizing and cleaving heterologous DNA at short, well-defined sequences called restriction sites. Bioinformatic evidence shows that restriction sites are significantly underrepresented in bacteriophage genomes, presumably because bacteriophages with fewer restriction sites are more likely to escape cleavage by restriction–modification systems. However, how mutations in restriction sites affect the likelihood of bacteriophage escape is unknown. Using the bacteriophage l and the restriction–modification system EcoRI, we show that while mutation effects at different restriction sites are unequal, they are independent. As a result, the probability of bacteriophage escape increases with each mutated restriction site. Our results experimentally support the role of restriction site avoidance as a response to selection imposed by restriction–modification systems and offer an insight into the events underlying the process of bacteriophage escape."}],"author":[{"last_name":"Pleska","id":"4569785E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7460-7479","first_name":"Maros","full_name":"Pleska, Maros"},{"first_name":"Calin C","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","last_name":"Guet"}],"ddc":["570"],"scopus_import":"1","day":"01","date_updated":"2026-06-18T18:54:20Z","fulldoi":"https://doi.org/10.1098/rsbl.2017.0646","pmid":1,"project":[{"name":"Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification Systems","grant_number":"RGY0079/2011","_id":"251BCBEC-B435-11E9-9278-68D0E5697425"},{"_id":"251D65D8-B435-11E9-9278-68D0E5697425","grant_number":"24210","name":"Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level"}],"issue":"12","status":"public","type":"journal_article","publist_id":"7253","department":[{"_id":"CaGu"}],"year":"2017","quality_controlled":"1","acknowledgement":"This work was funded by an HFSP Young Investigators' grant RGY0079/2011 (C.C.G.). M.P. is a recipient of a DOC Fellowship of the Austrian Academy of Science at the Institute of Science and Technology Austria."},{"article_processing_charge":"No","publication_status":"published","doi":"10.7554/eLife.28921","date_created":"2018-12-11T11:47:14Z","oa_version":"Published Version","publication_identifier":{"issn":["2050-084X"]},"article_number":"e28921","file_date_updated":"2020-07-14T12:47:10Z","author":[{"last_name":"Lagator","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","full_name":"Lagator, Mato","first_name":"Mato"},{"last_name":"Sarikas","full_name":"Sarikas, Srdjan","first_name":"Srdjan","id":"35F0286E-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Acar","first_name":"Hande","full_name":"Acar, Hande","orcid":"0000-0003-1986-9753","id":"2DDF136A-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-4624-4612","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","full_name":"Bollback, Jonathan P","first_name":"Jonathan P","last_name":"Bollback"},{"first_name":"Calin C","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","last_name":"Guet"}],"abstract":[{"text":"Most phenotypes are determined by molecular systems composed of specifically interacting molecules. However, unlike for individual components, little is known about the distributions of mutational effects of molecular systems as a whole. We ask how the distribution of mutational effects of a transcriptional regulatory system differs from the distributions of its components, by first independently, and then simultaneously, mutating a transcription factor and the associated promoter it represses. We find that the system distribution exhibits increased phenotypic variation compared to individual component distributions - an effect arising from intermolecular epistasis between the transcription factor and its DNA-binding site. In large part, this epistasis can be qualitatively attributed to the structure of the transcriptional regulatory system and could therefore be a common feature in prokaryotes. Counter-intuitively, intermolecular epistasis can alleviate the constraints of individual components, thereby increasing phenotypic variation that selection could act on and facilitating adaptive evolution. ","lang":"eng"}],"external_id":{"isi":["000425868200001"]},"language":[{"iso":"eng"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","corr_author":"1","isi":1,"intvolume":"         6","citation":{"short":"M. Lagator, S. Sarikas, H. Acar, J.P. Bollback, C.C. Guet, ELife 6 (2017).","ama":"Lagator M, Sarikas S, Acar H, Bollback JP, Guet CC. Regulatory network structure determines patterns of intermolecular epistasis. <i>eLife</i>. 2017;6. doi:<a href=\"https://doi.org/10.7554/eLife.28921\">10.7554/eLife.28921</a>","chicago":"Lagator, Mato, Srdjan Sarikas, Hande Acar, Jonathan P Bollback, and Calin C Guet. “Regulatory Network Structure Determines Patterns of Intermolecular Epistasis.” <i>ELife</i>. eLife Sciences Publications, 2017. <a href=\"https://doi.org/10.7554/eLife.28921\">https://doi.org/10.7554/eLife.28921</a>.","ieee":"M. Lagator, S. Sarikas, H. Acar, J. P. Bollback, and C. C. Guet, “Regulatory network structure determines patterns of intermolecular epistasis,” <i>eLife</i>, vol. 6. eLife Sciences Publications, 2017.","ista":"Lagator M, Sarikas S, Acar H, Bollback JP, Guet CC. 2017. Regulatory network structure determines patterns of intermolecular epistasis. eLife. 6, e28921.","apa":"Lagator, M., Sarikas, S., Acar, H., Bollback, J. P., &#38; Guet, C. C. (2017). Regulatory network structure determines patterns of intermolecular epistasis. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.28921\">https://doi.org/10.7554/eLife.28921</a>","mla":"Lagator, Mato, et al. “Regulatory Network Structure Determines Patterns of Intermolecular Epistasis.” <i>ELife</i>, vol. 6, e28921, eLife Sciences Publications, 2017, doi:<a href=\"https://doi.org/10.7554/eLife.28921\">10.7554/eLife.28921</a>."},"publication":"eLife","date_published":"2017-11-13T00:00:00Z","oa":1,"volume":6,"month":"11","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"title":"Regulatory network structure determines patterns of intermolecular epistasis","publisher":"eLife Sciences Publications","_id":"570","quality_controlled":"1","department":[{"_id":"CaGu"},{"_id":"JoBo"},{"_id":"NiBa"}],"publist_id":"7244","pubrep_id":"918","file":[{"date_updated":"2020-07-14T12:47:10Z","creator":"system","content_type":"application/pdf","file_name":"IST-2017-918-v1+1_elife-28921-figures-v3.pdf","relation":"main_file","file_id":"5096","date_created":"2018-12-12T10:14:42Z","access_level":"open_access","checksum":"273ab17f33305e4eaafd911ff88e7c5b","file_size":8453470},{"content_type":"application/pdf","file_name":"IST-2017-918-v1+2_elife-28921-v3.pdf","relation":"main_file","creator":"system","date_updated":"2020-07-14T12:47:10Z","file_size":1953221,"date_created":"2018-12-12T10:14:43Z","access_level":"open_access","file_id":"5097","checksum":"b433f90576c7be597cd43367946f8e7f"}],"year":"2017","ec_funded":1,"project":[{"_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"291734","name":"International IST Postdoc Fellowship Programme"},{"call_identifier":"H2020","grant_number":"648440","name":"Selective Barriers to Horizontal Gene Transfer","_id":"2578D616-B435-11E9-9278-68D0E5697425"}],"has_accepted_license":"1","status":"public","license":"https://creativecommons.org/licenses/by/4.0/","type":"journal_article","ddc":["576"],"scopus_import":"1","fulldoi":"https://doi.org/10.7554/eLife.28921","day":"13","date_updated":"2025-09-11T07:40:30Z"},{"citation":{"chicago":"Chait, Remy P, Jakob Ruess, Tobias Bergmiller, Gašper Tkačik, and Calin C Guet. “Shaping Bacterial Population Behavior through Computer Interfaced Control of Individual Cells.” <i>Nature Communications</i>. Nature Publishing Group, 2017. <a href=\"https://doi.org/10.1038/s41467-017-01683-1\">https://doi.org/10.1038/s41467-017-01683-1</a>.","ista":"Chait RP, Ruess J, Bergmiller T, Tkačik G, Guet CC. 2017. Shaping bacterial population behavior through computer interfaced control of individual cells. Nature Communications. 8(1), 1535.","ieee":"R. P. Chait, J. Ruess, T. Bergmiller, G. Tkačik, and C. C. Guet, “Shaping bacterial population behavior through computer interfaced control of individual cells,” <i>Nature Communications</i>, vol. 8, no. 1. Nature Publishing Group, 2017.","ama":"Chait RP, Ruess J, Bergmiller T, Tkačik G, Guet CC. Shaping bacterial population behavior through computer interfaced control of individual cells. <i>Nature Communications</i>. 2017;8(1). doi:<a href=\"https://doi.org/10.1038/s41467-017-01683-1\">10.1038/s41467-017-01683-1</a>","short":"R.P. Chait, J. Ruess, T. Bergmiller, G. Tkačik, C.C. Guet, Nature Communications 8 (2017).","mla":"Chait, Remy P., et al. “Shaping Bacterial Population Behavior through Computer Interfaced Control of Individual Cells.” <i>Nature Communications</i>, vol. 8, no. 1, 1535, Nature Publishing Group, 2017, doi:<a href=\"https://doi.org/10.1038/s41467-017-01683-1\">10.1038/s41467-017-01683-1</a>.","apa":"Chait, R. P., Ruess, J., Bergmiller, T., Tkačik, G., &#38; Guet, C. C. (2017). Shaping bacterial population behavior through computer interfaced control of individual cells. <i>Nature Communications</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/s41467-017-01683-1\">https://doi.org/10.1038/s41467-017-01683-1</a>"},"intvolume":"         8","publication":"Nature Communications","corr_author":"1","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","isi":1,"language":[{"iso":"eng"}],"abstract":[{"lang":"eng","text":"Bacteria in groups vary individually, and interact with other bacteria and the environment to produce population-level patterns of gene expression. Investigating such behavior in detail requires measuring and controlling populations at the single-cell level alongside precisely specified interactions and environmental characteristics. Here we present an automated, programmable platform that combines image-based gene expression and growth measurements with on-line optogenetic expression control for hundreds of individual Escherichia coli cells over days, in a dynamically adjustable environment. This integrated platform broadly enables experiments that bridge individual and population behaviors. We demonstrate: (i) population structuring by independent closed-loop control of gene expression in many individual cells, (ii) cell-cell variation control during antibiotic perturbation, (iii) hybrid bio-digital circuits in single cells, and freely specifiable digital communication between individual bacteria. These examples showcase the potential for real-time integration of theoretical models with measurement and control of many individual cells to investigate and engineer microbial population behavior."}],"author":[{"id":"3464AE84-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0876-3187","first_name":"Remy P","full_name":"Chait, Remy P","last_name":"Chait"},{"last_name":"Ruess","id":"4A245D00-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1615-3282","first_name":"Jakob","full_name":"Ruess, Jakob"},{"id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5396-4346","first_name":"Tobias","full_name":"Bergmiller, Tobias","last_name":"Bergmiller"},{"last_name":"Tkacik","first_name":"Gasper","full_name":"Tkacik, Gasper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455"},{"last_name":"Guet","full_name":"Guet, Calin C","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052"}],"external_id":{"isi":["000415323000008"]},"article_number":"1535","file_date_updated":"2020-07-14T12:47:20Z","publication_identifier":{"issn":["2041-1723"]},"oa_version":"Published Version","publication_status":"published","date_created":"2018-12-11T11:47:30Z","doi":"10.1038/s41467-017-01683-1","article_processing_charge":"Yes (in subscription journal)","_id":"613","publisher":"Nature Publishing Group","title":"Shaping bacterial population behavior through computer interfaced control of individual cells","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"volume":8,"month":"12","date_published":"2017-12-01T00:00:00Z","oa":1,"file":[{"date_updated":"2020-07-14T12:47:20Z","creator":"system","file_name":"IST-2017-911-v1+1_s41467-017-01683-1.pdf","relation":"main_file","content_type":"application/pdf","checksum":"44bb5d0229926c23a9955d9fe0f9723f","file_id":"5190","date_created":"2018-12-12T10:16:05Z","access_level":"open_access","file_size":1951699}],"year":"2017","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publist_id":"7191","pubrep_id":"911","acknowledgement":"We are grateful to M. Lang, H. Janovjak, M. Khammash, A. Milias-Argeitis, M. Rullan, G. Batt, A. Bosma-Moody, Aryan, S. Leibler, and members of the Guet and Tkačik groups for helpful discussion, comments, and suggestions. We thank A. Moglich, T. Mathes, J. Tabor, and S. Schmidl for kind gifts of strains, and R. Hauschild, B. Knep, M. Lang, T. Asenov, E. Papusheva, T. Menner, T. Adletzberger, and J. Merrin for technical assistance. The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007–2013) under REA grant agreement no. [291734]. (to R.C. and J.R.), Austrian Science Fund grant FWF P28844 (to G.T.), and internal IST Austria Interdisciplinary Project Support. J.R. acknowledges support from the Agence Nationale de la Recherche (ANR) under Grant Nos. ANR-16-CE33-0018 (MEMIP), ANR-16-CE12-0025 (COGEX) and ANR-10-BINF-06-01 (ICEBERG).","quality_controlled":"1","fulldoi":"https://doi.org/10.1038/s41467-017-01683-1","date_updated":"2025-09-11T07:34:12Z","day":"01","scopus_import":"1","ddc":["576","579"],"type":"journal_article","has_accepted_license":"1","status":"public","ec_funded":1,"issue":"1","project":[{"_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734","name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7"},{"_id":"254E9036-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"P28844-B27","name":"Biophysics of information processing in gene regulation"}]},{"volume":2017,"month":"09","oa":1,"date_published":"2017-09-21T00:00:00Z","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"title":"MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations","_id":"624","publisher":"PeerJ","oa_version":"Published Version","publication_identifier":{"issn":["2167-8359"]},"publication_status":"published","doi":"10.7717/peerj.3830","article_processing_charge":"No","date_created":"2018-12-11T11:47:33Z","external_id":{"isi":["000411665900002"]},"author":[{"first_name":"Nela","full_name":"Nikolic, Nela","orcid":"0000-0001-9068-6090","id":"42D9CABC-F248-11E8-B48F-1D18A9856A87","last_name":"Nikolic"},{"full_name":"Didara, Zrinka","first_name":"Zrinka","last_name":"Didara"},{"last_name":"Moll","first_name":"Isabella","full_name":"Moll, Isabella"}],"abstract":[{"text":"Bacteria adapt to adverse environmental conditions by altering gene expression patterns. Recently, a novel stress adaptation mechanism has been described that allows Escherichia coli to alter gene expression at the post-transcriptional level. The key player in this regulatory pathway is the endoribonuclease MazF, the toxin component of the toxin-antitoxin module mazEF that is triggered by various stressful conditions. In general, MazF degrades the majority of transcripts by cleaving at ACA sites, which results in the retardation of bacterial growth. Furthermore, MazF can process a small subset of mRNAs and render them leaderless by removing their ribosome binding site. MazF concomitantly modifies ribosomes, making them selective for the translation of leaderless mRNAs. In this study, we employed fluorescent reporter-systems to investigate mazEF expression during stressful conditions, and to infer consequences of the mRNA processing mediated by MazF on gene expression at the single-cell level. Our results suggest that mazEF transcription is maintained at low levels in single cells encountering adverse conditions, such as antibiotic stress or amino acid starvation. Moreover, using the grcA mRNA as a model for MazF-mediated mRNA processing, we found that MazF activation promotes heterogeneity in the grcA reporter expression, resulting in a subpopulation of cells with increased levels of GrcA reporter protein.","lang":"eng"}],"file_date_updated":"2020-07-14T12:47:24Z","article_number":"3830","isi":1,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","corr_author":"1","language":[{"iso":"eng"}],"publication":"PeerJ","citation":{"ama":"Nikolic N, Didara Z, Moll I. MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations. <i>PeerJ</i>. 2017;2017(9). doi:<a href=\"https://doi.org/10.7717/peerj.3830\">10.7717/peerj.3830</a>","short":"N. Nikolic, Z. Didara, I. Moll, PeerJ 2017 (2017).","ieee":"N. Nikolic, Z. Didara, and I. Moll, “MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations,” <i>PeerJ</i>, vol. 2017, no. 9. PeerJ, 2017.","chicago":"Nikolic, Nela, Zrinka Didara, and Isabella Moll. “MazF Activation Promotes Translational Heterogeneity of the GrcA MRNA in Escherichia Coli Populations.” <i>PeerJ</i>. PeerJ, 2017. <a href=\"https://doi.org/10.7717/peerj.3830\">https://doi.org/10.7717/peerj.3830</a>.","ista":"Nikolic N, Didara Z, Moll I. 2017. MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations. PeerJ. 2017(9), 3830.","apa":"Nikolic, N., Didara, Z., &#38; Moll, I. (2017). MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations. <i>PeerJ</i>. PeerJ. <a href=\"https://doi.org/10.7717/peerj.3830\">https://doi.org/10.7717/peerj.3830</a>","mla":"Nikolic, Nela, et al. “MazF Activation Promotes Translational Heterogeneity of the GrcA MRNA in Escherichia Coli Populations.” <i>PeerJ</i>, vol. 2017, no. 9, 3830, PeerJ, 2017, doi:<a href=\"https://doi.org/10.7717/peerj.3830\">10.7717/peerj.3830</a>."},"intvolume":"      2017","issue":"9","type":"journal_article","status":"public","has_accepted_license":"1","scopus_import":"1","ddc":["579"],"date_updated":"2025-09-11T07:30:06Z","day":"21","fulldoi":"https://doi.org/10.7717/peerj.3830","quality_controlled":"1","acknowledgement":"Austrian Science Fund (FWF): M1697, P22249; Swiss National Science Foundation (SNF): 145706; European Commission;FWF Special Research Program: RNA-REG F43","year":"2017","file":[{"content_type":"application/pdf","relation":"main_file","file_name":"IST-2017-909-v1+1_peerj-3830.pdf","creator":"system","date_updated":"2020-07-14T12:47:24Z","file_size":682064,"access_level":"open_access","file_id":"4908","date_created":"2018-12-12T10:11:51Z","checksum":"3d79ae6b6eabc90b0eaaed82ff3493b0"}],"pubrep_id":"909","department":[{"_id":"CaGu"}],"publist_id":"7172"},{"department":[{"_id":"CaGu"}],"publist_id":"7711","pubrep_id":"916","file":[{"file_size":18569590,"checksum":"33cfb59674e91f82e3738396d3fb3776","access_level":"open_access","date_created":"2018-12-12T10:08:48Z","file_id":"4710","relation":"main_file","file_name":"IST-2018-916-v1+3_2017_Pleska_Maros_Thesis.pdf","content_type":"application/pdf","creator":"system","date_updated":"2020-07-14T12:45:24Z"},{"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_name":"2017_Pleska_Maros_Thesis.docx","relation":"source_file","creator":"dernst","date_updated":"2020-07-14T12:45:24Z","file_size":2801649,"access_level":"closed","file_id":"6204","date_created":"2019-04-05T08:33:14Z","checksum":"dcc239968decb233e7f98cf1083d8c26"}],"supervisor":[{"last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","first_name":"Calin C","full_name":"Guet, Calin C"}],"year":"2017","acknowledgement":"During my PhD studies, I received help from many people, all of which unfortunately cannot be listed here. I thank them deeply and hope that I never made them regret their kindness.\r\nI would like to express my deepest gratitude to Călin Guet, who went far beyond his responsibilities as an advisor and was to me also a great mentor and a friend. Călin never questioned my potential or lacked compassion and I cannot thank him enough for cultivating in me an independent scientist. I was amazed by his ability to recognize the most fascinating scientific problems in objects of study that others would find mundane. I hope I adopted at least a fraction of this ability.\r\nI will be forever grateful to Bruce Levin for all his support and especially for giving me the best possible example of how one can practice excellent science with humor and style. Working with Bruce was a true privilege.\r\nI thank Jonathan Bollback and Gašper Tkačik for serving in my PhD committee and the Austrian Academy of Science for funding my PhD research via the DOC fellowship.\r\nI thank all our lab members: Tobias Bergmiller for his guidance, especially in the first years of my research, and for being a good friend throughout; Remy Chait for staying in the lab at unreasonable hours and for the good laughs at bad jokes we shared; Anna Staron for supportively listening to my whines whenever I had to run a gel; Magdalena Steinrück for her pioneering work in the lab; Kathrin Tomasek for keeping the entropic forces in check and for her FACS virtuosity; Isabella Tomanek for always being nice to me, no matter how much bench space I took from her.\r\nI thank all my collaborators: Reiko Okura and Yuichi Wakamoto for performing and analyzing the microfluidic experiments; Long Qian and Edo Kussell for their bioinformatics analysis; Dominik Refardt for the λ kan phage; Moritz for his help with the mathematical modeling. I thank Fabienne Jesse for her tireless editorial work on all our manuscripts.\r\nFinally, I would like to thank my family and especially my wife Edita, who sacrificed a lot so that I can pursue my goals and dreams.\r\n","fulldoi":"https://doi.org/10.15479/AT:ISTA:th_916","day":"01","date_updated":"2026-06-18T18:54:19Z","ddc":["576","579"],"has_accepted_license":"1","status":"public","type":"dissertation","page":"126","project":[{"grant_number":"24210","name":"Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level","_id":"251D65D8-B435-11E9-9278-68D0E5697425"}],"degree_awarded":"PhD","alternative_title":["ISTA Thesis"],"citation":{"ista":"Pleska M. 2017. Biology of restriction-modification systems at the single-cell and population level. Institute of Science and Technology Austria.","ieee":"M. Pleska, “Biology of restriction-modification systems at the single-cell and population level,” Institute of Science and Technology Austria, 2017.","chicago":"Pleska, Maros. “Biology of Restriction-Modification Systems at the Single-Cell and Population Level.” Institute of Science and Technology Austria, 2017. <a href=\"https://doi.org/10.15479/AT:ISTA:th_916\">https://doi.org/10.15479/AT:ISTA:th_916</a>.","ama":"Pleska M. Biology of restriction-modification systems at the single-cell and population level. 2017. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:th_916\">10.15479/AT:ISTA:th_916</a>","short":"M. Pleska, Biology of Restriction-Modification Systems at the Single-Cell and Population Level, Institute of Science and Technology Austria, 2017.","apa":"Pleska, M. (2017). <i>Biology of restriction-modification systems at the single-cell and population level</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:th_916\">https://doi.org/10.15479/AT:ISTA:th_916</a>","mla":"Pleska, Maros. <i>Biology of Restriction-Modification Systems at the Single-Cell and Population Level</i>. Institute of Science and Technology Austria, 2017, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:th_916\">10.15479/AT:ISTA:th_916</a>."},"related_material":{"record":[{"id":"457","status":"public","relation":"part_of_dissertation"},{"status":"public","id":"1243","relation":"part_of_dissertation"},{"relation":"part_of_dissertation","id":"561","status":"public"}]},"language":[{"iso":"eng"}],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","corr_author":"1","file_date_updated":"2020-07-14T12:45:24Z","abstract":[{"lang":"eng","text":"Restriction-modification (RM) represents the simplest and possibly the most widespread mechanism of self/non-self discrimination in nature. In order to provide bacteria with immunity against bacteriophages and other parasitic genetic elements, RM systems rely on a balance between two enzymes: the restriction enzyme, which cleaves non-self DNA at specific restriction sites, and the modification enzyme, which tags the host’s DNA as self and thus protects it from cleavage. In this thesis, I use population and single-cell level experiments in combination with mathematical modeling to study different aspects of the interplay between RM systems, bacteria and bacteriophages. First, I analyze how mutations in phage restriction sites affect the probability of phage escape – an inherently stochastic process, during which phages accidently get modified instead of restricted. Next, I use single-cell experiments to show that RM systems can, with a low probability, attack the genome of their bacterial host and that this primitive form of autoimmunity leads to a tradeoff between the evolutionary cost and benefit of RM systems. Finally, I investigate the nature of interactions between bacteria, RM systems and temperate bacteriophages to find that, as a consequence of phage escape and its impact on population dynamics, RM systems can promote acquisition of symbiotic bacteriophages, rather than limit it. The results presented here uncover new fundamental biological properties of RM systems and highlight their importance in the ecology and evolution of bacteria, bacteriophages and their interactions."}],"author":[{"last_name":"Pleska","first_name":"Maros","full_name":"Pleska, Maros","id":"4569785E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7460-7479"}],"publication_status":"published","doi":"10.15479/AT:ISTA:th_916","article_processing_charge":"No","date_created":"2018-12-11T11:45:10Z","publication_identifier":{"issn":["2663-337X"]},"oa_version":"Published Version","publisher":"Institute of Science and Technology Austria","_id":"202","title":"Biology of restriction-modification systems at the single-cell and population level","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"date_published":"2017-10-01T00:00:00Z","OA_place":"publisher","oa":1,"month":"10"},{"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"volume":"81C","month":"06","date_published":"2017-06-01T00:00:00Z","oa":1,"_id":"1007","publisher":"International Federation of Automatic Control","title":"Zeros of nonlinear systems with input invariances","abstract":[{"lang":"eng","text":"A nonlinear system possesses an invariance with respect to a set of transformations if its output dynamics remain invariant when transforming the input, and adjusting the initial condition accordingly. Most research has focused on invariances with respect to time-independent pointwise transformations like translational-invariance (u(t) -&gt; u(t) + p, p in R) or scale-invariance (u(t) -&gt; pu(t), p in R&gt;0). In this article, we introduce the concept of s0-invariances with respect to continuous input transformations exponentially growing/decaying over time. We show that s0-invariant systems not only encompass linear time-invariant (LTI) systems with transfer functions having an irreducible zero at s0 in R, but also that the input/output relationship of nonlinear s0-invariant systems possesses properties well known from their linear counterparts. Furthermore, we extend the concept of s0-invariances to second- and higher-order s0-invariances, corresponding to invariances with respect to transformations of the time-derivatives of the input, and encompassing LTI systems with zeros of multiplicity two or higher. Finally, we show that nth-order 0-invariant systems realize – under mild conditions – nth-order nonlinear differential operators: when excited by an input of a characteristic functional form, the system’s output converges to a constant value only depending on the nth (nonlinear) derivative of the input."}],"author":[{"last_name":"Lang","id":"29E0800A-F248-11E8-B48F-1D18A9856A87","full_name":"Lang, Moritz","first_name":"Moritz"},{"full_name":"Sontag, Eduardo","first_name":"Eduardo","last_name":"Sontag"}],"external_id":{"isi":["000403513900006"]},"file_date_updated":"2018-12-12T10:11:29Z","oa_version":"Published Version","publication_identifier":{"issn":["0005-1098"]},"article_processing_charge":"Yes (in subscription journal)","date_created":"2018-12-11T11:49:39Z","publication_status":"published","doi":"10.1016/j.automatica.2017.03.030","citation":{"short":"M. Lang, E. Sontag, Automatica 81C (2017) 46–55.","ama":"Lang M, Sontag E. Zeros of nonlinear systems with input invariances. <i>Automatica</i>. 2017;81C:46-55. doi:<a href=\"https://doi.org/10.1016/j.automatica.2017.03.030\">10.1016/j.automatica.2017.03.030</a>","chicago":"Lang, Moritz, and Eduardo Sontag. “Zeros of Nonlinear Systems with Input Invariances.” <i>Automatica</i>. International Federation of Automatic Control, 2017. <a href=\"https://doi.org/10.1016/j.automatica.2017.03.030\">https://doi.org/10.1016/j.automatica.2017.03.030</a>.","ieee":"M. Lang and E. Sontag, “Zeros of nonlinear systems with input invariances,” <i>Automatica</i>, vol. 81C. International Federation of Automatic Control, pp. 46–55, 2017.","ista":"Lang M, Sontag E. 2017. Zeros of nonlinear systems with input invariances. Automatica. 81C, 46–55.","apa":"Lang, M., &#38; Sontag, E. (2017). Zeros of nonlinear systems with input invariances. <i>Automatica</i>. International Federation of Automatic Control. <a href=\"https://doi.org/10.1016/j.automatica.2017.03.030\">https://doi.org/10.1016/j.automatica.2017.03.030</a>","mla":"Lang, Moritz, and Eduardo Sontag. “Zeros of Nonlinear Systems with Input Invariances.” <i>Automatica</i>, vol. 81C, International Federation of Automatic Control, 2017, pp. 46–55, doi:<a href=\"https://doi.org/10.1016/j.automatica.2017.03.030\">10.1016/j.automatica.2017.03.030</a>."},"publication":"Automatica","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","isi":1,"language":[{"iso":"eng"}],"type":"journal_article","has_accepted_license":"1","status":"public","ec_funded":1,"page":"46 - 55","project":[{"name":"International IST Postdoc Fellowship Programme","grant_number":"291734","call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425"}],"fulldoi":"https://doi.org/10.1016/j.automatica.2017.03.030","day":"01","date_updated":"2025-04-15T06:50:01Z","scopus_import":"1","ddc":["000"],"quality_controlled":"1","file":[{"file_size":1401954,"date_created":"2018-12-12T10:11:29Z","access_level":"open_access","file_id":"4884","content_type":"application/pdf","relation":"main_file","file_name":"IST-2017-813-v1+1_ZerosOfNonlinearSystems.pdf","creator":"system","date_updated":"2018-12-12T10:11:29Z"}],"year":"2017","publist_id":"6391","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"pubrep_id":"813"},{"author":[{"id":"345D25EC-F248-11E8-B48F-1D18A9856A87","first_name":"Mato","full_name":"Lagator, Mato","last_name":"Lagator"},{"last_name":"Paixao","full_name":"Paixao, Tiago","first_name":"Tiago","orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Nicholas H","full_name":"Barton, Nicholas H","orcid":"0000-0002-8548-5240","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","last_name":"Barton"},{"id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4624-4612","full_name":"Bollback, Jonathan P","first_name":"Jonathan P","last_name":"Bollback"},{"full_name":"Guet, Calin C","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","last_name":"Guet"}],"abstract":[{"text":"Understanding the relation between genotype and phenotype remains a major challenge. The difficulty of predicting individual mutation effects, and particularly the interactions between them, has prevented the development of a comprehensive theory that links genotypic changes to their phenotypic effects. We show that a general thermodynamic framework for gene regulation, based on a biophysical understanding of protein-DNA binding, accurately predicts the sign of epistasis in a canonical cis-regulatory element consisting of overlapping RNA polymerase and repressor binding sites. Sign and magnitude of individual mutation effects are sufficient to predict the sign of epistasis and its environmental dependence. Thus, the thermodynamic model offers the correct null prediction for epistasis between mutations across DNA-binding sites. Our results indicate that a predictive theory for the effects of cis-regulatory mutations is possible from first principles, as long as the essential molecular mechanisms and the constraints these impose on a biological system are accounted for.","lang":"eng"}],"external_id":{"isi":["000404024800001"]},"article_number":"e25192","file_date_updated":"2020-07-14T12:48:16Z","oa_version":"Published Version","publication_identifier":{"issn":["2050-084X"]},"doi":"10.7554/eLife.25192","article_processing_charge":"Yes","date_created":"2018-12-11T11:49:23Z","publication_status":"published","intvolume":"         6","citation":{"mla":"Lagator, Mato, et al. “On the Mechanistic Nature of Epistasis in a Canonical Cis-Regulatory Element.” <i>ELife</i>, vol. 6, e25192, eLife Sciences Publications, 2017, doi:<a href=\"https://doi.org/10.7554/eLife.25192\">10.7554/eLife.25192</a>.","apa":"Lagator, M., Paixao, T., Barton, N. H., Bollback, J. P., &#38; Guet, C. C. (2017). On the mechanistic nature of epistasis in a canonical cis-regulatory element. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.25192\">https://doi.org/10.7554/eLife.25192</a>","chicago":"Lagator, Mato, Tiago Paixao, Nicholas H Barton, Jonathan P Bollback, and Calin C Guet. “On the Mechanistic Nature of Epistasis in a Canonical Cis-Regulatory Element.” <i>ELife</i>. eLife Sciences Publications, 2017. <a href=\"https://doi.org/10.7554/eLife.25192\">https://doi.org/10.7554/eLife.25192</a>.","ista":"Lagator M, Paixao T, Barton NH, Bollback JP, Guet CC. 2017. On the mechanistic nature of epistasis in a canonical cis-regulatory element. eLife. 6, e25192.","ieee":"M. Lagator, T. Paixao, N. H. Barton, J. P. Bollback, and C. C. Guet, “On the mechanistic nature of epistasis in a canonical cis-regulatory element,” <i>eLife</i>, vol. 6. eLife Sciences Publications, 2017.","ama":"Lagator M, Paixao T, Barton NH, Bollback JP, Guet CC. On the mechanistic nature of epistasis in a canonical cis-regulatory element. <i>eLife</i>. 2017;6. doi:<a href=\"https://doi.org/10.7554/eLife.25192\">10.7554/eLife.25192</a>","short":"M. Lagator, T. Paixao, N.H. Barton, J.P. Bollback, C.C. Guet, ELife 6 (2017)."},"publication":"eLife","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","isi":1,"language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"month":"05","volume":6,"date_published":"2017-05-18T00:00:00Z","oa":1,"_id":"954","publisher":"eLife Sciences Publications","title":"On the mechanistic nature of epistasis in a canonical cis-regulatory element","quality_controlled":"1","file":[{"file_id":"5306","date_created":"2018-12-12T10:17:49Z","access_level":"open_access","checksum":"59cdd4400fb41280122d414fea971546","file_size":2441529,"creator":"system","content_type":"application/pdf","file_name":"IST-2017-841-v1+1_elife-25192-v2.pdf","relation":"main_file","date_updated":"2020-07-14T12:48:16Z"},{"date_updated":"2020-07-14T12:48:16Z","creator":"system","relation":"main_file","file_name":"IST-2017-841-v1+2_elife-25192-figures-v2.pdf","content_type":"application/pdf","checksum":"b69024880558b858eb8c5d47a92b6377","file_id":"5307","access_level":"open_access","date_created":"2018-12-12T10:17:50Z","file_size":3752660}],"year":"2017","publist_id":"6460","department":[{"_id":"CaGu"},{"_id":"NiBa"},{"_id":"JoBo"}],"pubrep_id":"841","type":"journal_article","has_accepted_license":"1","status":"public","ec_funded":1,"project":[{"call_identifier":"FP7","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","grant_number":"618091","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425"},{"_id":"25681D80-B435-11E9-9278-68D0E5697425","name":"International IST Postdoc Fellowship Programme","grant_number":"291734","call_identifier":"FP7"},{"_id":"2578D616-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"648440","name":"Selective Barriers to Horizontal Gene Transfer"}],"fulldoi":"https://doi.org/10.7554/eLife.25192","day":"18","date_updated":"2025-07-10T12:01:50Z","scopus_import":"1","ddc":["576"]},{"publication_identifier":{"issn":["2050-084X"]},"oa_version":"Published Version","date_created":"2018-12-11T11:47:44Z","publication_status":"published","doi":"10.7554/eLife.23136","article_processing_charge":"No","external_id":{"isi":["000398680700001"]},"author":[{"last_name":"Renault","full_name":"Renault, Thibaud","first_name":"Thibaud"},{"full_name":"Abraham, Anthony","first_name":"Anthony","last_name":"Abraham"},{"id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5396-4346","first_name":"Tobias","full_name":"Bergmiller, Tobias","last_name":"Bergmiller"},{"last_name":"Paradis","full_name":"Paradis, Guillaume","first_name":"Guillaume"},{"full_name":"Rainville, Simon","first_name":"Simon","last_name":"Rainville"},{"full_name":"Charpentier, Emmanuelle","first_name":"Emmanuelle","last_name":"Charpentier"},{"last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","first_name":"Calin C","full_name":"Guet, Calin C"},{"last_name":"Tu","full_name":"Tu, Yuhai","first_name":"Yuhai"},{"last_name":"Namba","first_name":"Keiichi","full_name":"Namba, Keiichi"},{"first_name":"James","full_name":"Keener, James","last_name":"Keener"},{"last_name":"Minamino","first_name":"Tohru","full_name":"Minamino, Tohru"},{"last_name":"Erhardt","first_name":"Marc","full_name":"Erhardt, Marc"}],"abstract":[{"lang":"eng","text":"The bacterial flagellum is a self-assembling nanomachine. The external flagellar filament, several times longer than a bacterial cell body, is made of a few tens of thousands subunits of a single protein: flagellin. A fundamental problem concerns the molecular mechanism of how the flagellum grows outside the cell, where no discernible energy source is available. Here, we monitored the dynamic assembly of individual flagella using in situ labelling and real-time immunostaining of elongating flagellar filaments. We report that the rate of flagellum growth, initially ~1,700 amino acids per second, decreases with length and that the previously proposed chain mechanism does not contribute to the filament elongation dynamics. Inhibition of the proton motive force-dependent export apparatus revealed a major contribution of substrate injection in driving filament elongation. The combination of experimental and mathematical evidence demonstrates that a simple, injection-diffusion mechanism controls bacterial flagella growth outside the cell."}],"file_date_updated":"2020-07-14T12:47:33Z","article_number":"e23136","isi":1,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","language":[{"iso":"eng"}],"publication":"eLife","citation":{"mla":"Renault, Thibaud, et al. “Bacterial Flagella Grow through an Injection Diffusion Mechanism.” <i>ELife</i>, vol. 6, e23136, eLife Sciences Publications, 2017, doi:<a href=\"https://doi.org/10.7554/eLife.23136\">10.7554/eLife.23136</a>.","apa":"Renault, T., Abraham, A., Bergmiller, T., Paradis, G., Rainville, S., Charpentier, E., … Erhardt, M. (2017). Bacterial flagella grow through an injection diffusion mechanism. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.23136\">https://doi.org/10.7554/eLife.23136</a>","short":"T. Renault, A. Abraham, T. Bergmiller, G. Paradis, S. Rainville, E. Charpentier, C.C. Guet, Y. Tu, K. Namba, J. Keener, T. Minamino, M. Erhardt, ELife 6 (2017).","ama":"Renault T, Abraham A, Bergmiller T, et al. Bacterial flagella grow through an injection diffusion mechanism. <i>eLife</i>. 2017;6. doi:<a href=\"https://doi.org/10.7554/eLife.23136\">10.7554/eLife.23136</a>","chicago":"Renault, Thibaud, Anthony Abraham, Tobias Bergmiller, Guillaume Paradis, Simon Rainville, Emmanuelle Charpentier, Calin C Guet, et al. “Bacterial Flagella Grow through an Injection Diffusion Mechanism.” <i>ELife</i>. eLife Sciences Publications, 2017. <a href=\"https://doi.org/10.7554/eLife.23136\">https://doi.org/10.7554/eLife.23136</a>.","ieee":"T. Renault <i>et al.</i>, “Bacterial flagella grow through an injection diffusion mechanism,” <i>eLife</i>, vol. 6. eLife Sciences Publications, 2017.","ista":"Renault T, Abraham A, Bergmiller T, Paradis G, Rainville S, Charpentier E, Guet CC, Tu Y, Namba K, Keener J, Minamino T, Erhardt M. 2017. Bacterial flagella grow through an injection diffusion mechanism. eLife. 6, e23136."},"intvolume":"         6","month":"03","volume":6,"oa":1,"date_published":"2017-03-06T00:00:00Z","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"title":"Bacterial flagella grow through an injection diffusion mechanism","_id":"655","publisher":"eLife Sciences Publications","quality_controlled":"1","year":"2017","file":[{"date_updated":"2020-07-14T12:47:33Z","creator":"system","content_type":"application/pdf","relation":"main_file","file_name":"IST-2017-904-v1+1_elife-23136-v2.pdf","date_created":"2018-12-12T10:08:53Z","file_id":"4716","access_level":"open_access","checksum":"39e1c3e82ddac83a30422fa72fa1a383","file_size":5520359},{"creator":"system","content_type":"application/pdf","file_name":"IST-2017-904-v1+2_elife-23136-figures-v2.pdf","relation":"main_file","date_updated":"2020-07-14T12:47:33Z","access_level":"open_access","file_id":"4717","date_created":"2018-12-12T10:08:54Z","checksum":"a6d542253028f52e00aa29739ddffe8f","file_size":11242920}],"pubrep_id":"904","publist_id":"7082","department":[{"_id":"CaGu"}],"type":"journal_article","status":"public","has_accepted_license":"1","scopus_import":"1","ddc":["579"],"date_updated":"2025-09-11T07:11:19Z","day":"06","fulldoi":"https://doi.org/10.7554/eLife.23136"},{"volume":356,"month":"04","date_published":"2017-04-21T00:00:00Z","_id":"665","publisher":"American Association for the Advancement of Science","article_type":"original","title":"Biased partitioning of the multidrug efflux pump AcrAB TolC underlies long lived phenotypic heterogeneity","author":[{"last_name":"Bergmiller","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5396-4346","full_name":"Bergmiller, Tobias","first_name":"Tobias"},{"full_name":"Andersson, Anna M","first_name":"Anna M","orcid":"0000-0003-2912-6769","id":"2B8A40DA-F248-11E8-B48F-1D18A9856A87","last_name":"Andersson"},{"last_name":"Tomasek","full_name":"Tomasek, Kathrin","first_name":"Kathrin","orcid":"0000-0003-3768-877X","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Balleza, Enrique","first_name":"Enrique","last_name":"Balleza"},{"last_name":"Kiviet","full_name":"Kiviet, Daniel","first_name":"Daniel"},{"last_name":"Hauschild","full_name":"Hauschild, Robert","first_name":"Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9843-3522"},{"last_name":"Tkacik","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","full_name":"Tkacik, Gasper","first_name":"Gasper"},{"first_name":"Calin C","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","last_name":"Guet"}],"abstract":[{"lang":"eng","text":"The molecular mechanisms underlying phenotypic variation in isogenic bacterial populations remain poorly understood.We report that AcrAB-TolC, the main multidrug efflux pump of Escherichia coli, exhibits a strong partitioning bias for old cell poles by a segregation mechanism that is mediated by ternary AcrAB-TolC complex formation. Mother cells inheriting old poles are phenotypically distinct and display increased drug efflux activity relative to daughters. Consequently, we find systematic and long-lived growth differences between mother and daughter cells in the presence of subinhibitory drug concentrations. A simple model for biased partitioning predicts a population structure of long-lived and highly heterogeneous phenotypes. This straightforward mechanism of generating sustained growth rate differences at subinhibitory antibiotic concentrations has implications for understanding the emergence of multidrug resistance in bacteria."}],"external_id":{"isi":["000399540100060"]},"oa_version":"None","publication_identifier":{"issn":["0036-8075"]},"doi":"10.1126/science.aaf4762","publication_status":"published","article_processing_charge":"No","date_created":"2018-12-11T11:47:48Z","intvolume":"       356","citation":{"ama":"Bergmiller T, Andersson AM, Tomasek K, et al. Biased partitioning of the multidrug efflux pump AcrAB TolC underlies long lived phenotypic heterogeneity. <i>Science</i>. 2017;356(6335):311-315. doi:<a href=\"https://doi.org/10.1126/science.aaf4762\">10.1126/science.aaf4762</a>","short":"T. Bergmiller, A.M. Andersson, K. Tomasek, E. Balleza, D. Kiviet, R. Hauschild, G. Tkačik, C.C. Guet, Science 356 (2017) 311–315.","ista":"Bergmiller T, Andersson AM, Tomasek K, Balleza E, Kiviet D, Hauschild R, Tkačik G, Guet CC. 2017. Biased partitioning of the multidrug efflux pump AcrAB TolC underlies long lived phenotypic heterogeneity. Science. 356(6335), 311–315.","chicago":"Bergmiller, Tobias, Anna M Andersson, Kathrin Tomasek, Enrique Balleza, Daniel Kiviet, Robert Hauschild, Gašper Tkačik, and Calin C Guet. “Biased Partitioning of the Multidrug Efflux Pump AcrAB TolC Underlies Long Lived Phenotypic Heterogeneity.” <i>Science</i>. 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Paixao, (2017)."},"date_published":"2017-07-18T00:00:00Z","month":"07","status":"public","type":"research_data_reference","title":"Modelling and simulation details","publisher":"Public Library of Science","fulldoi":"https://doi.org/10.1371/journal.pcbi.1005609.s001","_id":"9849","day":"18","date_updated":"2025-09-10T11:11:52Z"},{"status":"public","type":"research_data_reference","date_published":"2017-07-18T00:00:00Z","month":"07","publisher":"Public Library of Science","_id":"9850","day":"18","date_updated":"2025-09-10T11:11:52Z","fulldoi":"https://doi.org/10.1371/journal.pcbi.1005609.s002","title":"Extensions of the model","author":[{"id":"4342E402-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2519-8004","full_name":"Lukacisinova, Marta","first_name":"Marta","last_name":"Lukacisinova"},{"last_name":"Novak","id":"461468AE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2519-824X","first_name":"Sebastian","full_name":"Novak, Sebastian"},{"id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2361-3953","full_name":"Paixao, Tiago","first_name":"Tiago","last_name":"Paixao"}],"abstract":[{"lang":"eng","text":"In this text, we discuss how a cost of resistance and the possibility of lethal mutations impact our model."}],"doi":"10.1371/journal.pcbi.1005609.s002","article_processing_charge":"No","date_created":"2021-08-09T14:05:24Z","oa_version":"Published Version","citation":{"apa":"Lukacisinova, M., Novak, S., &#38; Paixao, T. (2017). Extensions of the model. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pcbi.1005609.s002\">https://doi.org/10.1371/journal.pcbi.1005609.s002</a>","mla":"Lukacisinova, Marta, et al. <i>Extensions of the Model</i>. Public Library of Science, 2017, doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1005609.s002\">10.1371/journal.pcbi.1005609.s002</a>.","ama":"Lukacisinova M, Novak S, Paixao T. Extensions of the model. 2017. doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1005609.s002\">10.1371/journal.pcbi.1005609.s002</a>","short":"M. Lukacisinova, S. Novak, T. Paixao, (2017).","ista":"Lukacisinova M, Novak S, Paixao T. 2017. Extensions of the model, Public Library of Science, <a href=\"https://doi.org/10.1371/journal.pcbi.1005609.s002\">10.1371/journal.pcbi.1005609.s002</a>.","ieee":"M. Lukacisinova, S. Novak, and T. Paixao, “Extensions of the model.” Public Library of Science, 2017.","chicago":"Lukacisinova, Marta, Sebastian Novak, and Tiago Paixao. “Extensions of the Model.” Public Library of Science, 2017. <a href=\"https://doi.org/10.1371/journal.pcbi.1005609.s002\">https://doi.org/10.1371/journal.pcbi.1005609.s002</a>."},"department":[{"_id":"ToBo"},{"_id":"CaGu"},{"_id":"NiBa"}],"related_material":{"record":[{"id":"696","status":"public","relation":"used_in_publication"}]},"year":"2017","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf"},{"type":"research_data_reference","status":"public","month":"07","date_published":"2017-07-18T00:00:00Z","_id":"9851","date_updated":"2025-09-10T11:11:52Z","day":"18","fulldoi":"https://doi.org/10.1371/journal.pcbi.1005609.s003","publisher":"Public Library of Science","title":"Heuristic prediction for multiple stresses","author":[{"last_name":"Lukacisinova","first_name":"Marta","full_name":"Lukacisinova, Marta","orcid":"0000-0002-2519-8004","id":"4342E402-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Novak","full_name":"Novak, Sebastian","first_name":"Sebastian","id":"461468AE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2519-824X"},{"orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","full_name":"Paixao, Tiago","first_name":"Tiago","last_name":"Paixao"}],"abstract":[{"text":"Based on the intuitive derivation of the dynamics of SIM allele frequency pM in the main text, we present a heuristic prediction for the long-term SIM allele frequencies with χ > 1 stresses and compare it to numerical simulations.","lang":"eng"}],"oa_version":"Published Version","date_created":"2021-08-09T14:08:14Z","article_processing_charge":"No","doi":"10.1371/journal.pcbi.1005609.s003","citation":{"mla":"Lukacisinova, Marta, et al. <i>Heuristic Prediction for Multiple Stresses</i>. Public Library of Science, 2017, doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1005609.s003\">10.1371/journal.pcbi.1005609.s003</a>.","apa":"Lukacisinova, M., Novak, S., &#38; Paixao, T. (2017). Heuristic prediction for multiple stresses. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pcbi.1005609.s003\">https://doi.org/10.1371/journal.pcbi.1005609.s003</a>","ieee":"M. Lukacisinova, S. Novak, and T. Paixao, “Heuristic prediction for multiple stresses.” Public Library of Science, 2017.","ista":"Lukacisinova M, Novak S, Paixao T. 2017. Heuristic prediction for multiple stresses, Public Library of Science, <a href=\"https://doi.org/10.1371/journal.pcbi.1005609.s003\">10.1371/journal.pcbi.1005609.s003</a>.","chicago":"Lukacisinova, Marta, Sebastian Novak, and Tiago Paixao. “Heuristic Prediction for Multiple Stresses.” Public Library of Science, 2017. <a href=\"https://doi.org/10.1371/journal.pcbi.1005609.s003\">https://doi.org/10.1371/journal.pcbi.1005609.s003</a>.","short":"M. Lukacisinova, S. Novak, T. Paixao, (2017).","ama":"Lukacisinova M, Novak S, Paixao T. Heuristic prediction for multiple stresses. 2017. doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1005609.s003\">10.1371/journal.pcbi.1005609.s003</a>"},"year":"2017","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","related_material":{"record":[{"relation":"used_in_publication","status":"public","id":"696"}]},"department":[{"_id":"ToBo"},{"_id":"CaGu"},{"_id":"NiBa"}]},{"fulldoi":"https://doi.org/10.1371/journal.pcbi.1005609.s004","day":"18","_id":"9852","date_updated":"2025-09-10T11:11:52Z","publisher":"Public Library of Science","title":"Resistance frequencies for different combination strategies","type":"research_data_reference","status":"public","month":"07","date_published":"2017-07-18T00:00:00Z","citation":{"ama":"Lukacisinova M, Novak S, Paixao T. Resistance frequencies for different combination strategies. 2017. doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1005609.s004\">10.1371/journal.pcbi.1005609.s004</a>","short":"M. Lukacisinova, S. Novak, T. Paixao, (2017).","chicago":"Lukacisinova, Marta, Sebastian Novak, and Tiago Paixao. “Resistance Frequencies for Different Combination Strategies.” Public Library of Science, 2017. <a href=\"https://doi.org/10.1371/journal.pcbi.1005609.s004\">https://doi.org/10.1371/journal.pcbi.1005609.s004</a>.","ieee":"M. Lukacisinova, S. Novak, and T. Paixao, “Resistance frequencies for different combination strategies.” Public Library of Science, 2017.","ista":"Lukacisinova M, Novak S, Paixao T. 2017. Resistance frequencies for different combination strategies, Public Library of Science, <a href=\"https://doi.org/10.1371/journal.pcbi.1005609.s004\">10.1371/journal.pcbi.1005609.s004</a>.","apa":"Lukacisinova, M., Novak, S., &#38; Paixao, T. (2017). Resistance frequencies for different combination strategies. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pcbi.1005609.s004\">https://doi.org/10.1371/journal.pcbi.1005609.s004</a>","mla":"Lukacisinova, Marta, et al. <i>Resistance Frequencies for Different Combination Strategies</i>. Public Library of Science, 2017, doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1005609.s004\">10.1371/journal.pcbi.1005609.s004</a>."},"user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","year":"2017","department":[{"_id":"ToBo"},{"_id":"CaGu"},{"_id":"NiBa"}],"related_material":{"record":[{"relation":"used_in_publication","status":"public","id":"696"}]},"abstract":[{"lang":"eng","text":"We show how different combination strategies affect the fraction of individuals that are multi-resistant."}],"author":[{"last_name":"Lukacisinova","id":"4342E402-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2519-8004","first_name":"Marta","full_name":"Lukacisinova, Marta"},{"first_name":"Sebastian","full_name":"Novak, Sebastian","orcid":"0000-0002-2519-824X","id":"461468AE-F248-11E8-B48F-1D18A9856A87","last_name":"Novak"},{"last_name":"Paixao","first_name":"Tiago","full_name":"Paixao, Tiago","orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87"}],"oa_version":"Published Version","article_processing_charge":"No","date_created":"2021-08-09T14:11:40Z","doi":"10.1371/journal.pcbi.1005609.s004"},{"type":"journal_article","status":"public","has_accepted_license":"1","scopus_import":"1","ddc":["576"],"date_updated":"2026-10-16T22:30:17Z","day":"25","fulldoi":"https://doi.org/10.7554/eLife.25100","quality_controlled":"1","year":"2017","file":[{"access_level":"open_access","file_id":"4975","date_created":"2018-12-12T10:12:54Z","checksum":"6b908b5db9f61f6820ebd7f8fa815571","file_size":2092088,"date_updated":"2020-07-14T12:47:48Z","creator":"system","content_type":"application/pdf","relation":"main_file","file_name":"IST-2017-890-v1+1_elife-25100-v1.pdf"},{"content_type":"application/pdf","relation":"main_file","file_name":"IST-2017-890-v1+2_elife-25100-figures-v1.pdf","creator":"system","date_updated":"2020-07-14T12:47:48Z","file_size":3428681,"file_id":"4976","access_level":"open_access","date_created":"2018-12-12T10:12:55Z","checksum":"ca21530389b720243552678125fdba35"}],"pubrep_id":"890","department":[{"_id":"CaGu"}],"publist_id":"6990","volume":6,"month":"07","oa":1,"date_published":"2017-07-25T00:00:00Z","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"title":"Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection","_id":"704","publisher":"eLife Sciences Publications","publication_identifier":{"issn":["2050-084X"]},"oa_version":"Published Version","date_created":"2018-12-11T11:48:01Z","publication_status":"published","article_processing_charge":"No","doi":"10.7554/eLife.25100","external_id":{"isi":["000406183700001"]},"author":[{"first_name":"Magdalena","full_name":"Steinrück, Magdalena","id":"2C023F40-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1229-9719","last_name":"Steinrück"},{"last_name":"Guet","full_name":"Guet, Calin C","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"}],"abstract":[{"lang":"eng","text":"How the organization of genes on a chromosome shapes adaptation is essential for understanding evolutionary paths. Here, we investigate how adaptation to rapidly increasing levels of antibiotic depends on the chromosomal neighborhood of a drug-resistance gene inserted at different positions of the Escherichia coli chromosome. Using a dual-fluorescence reporter that allows us to distinguish gene amplifications from other up-mutations, we track in real-time adaptive changes in expression of the drug-resistance gene. We find that the relative contribution of several mutation types differs systematically between loci due to properties of neighboring genes: essentiality, expression, orientation, termination, and presence of duplicates. These properties determine rate and fitness effects of gene amplification, deletions, and mutations compromising transcriptional termination. Thus, the adaptive potential of a gene under selection is a system-property with a complex genetic basis that is specific for each chromosomal locus, and it can be inferred from detailed functional and genomic data."}],"file_date_updated":"2020-07-14T12:47:48Z","article_number":"e25100","isi":1,"corr_author":"1","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","language":[{"iso":"eng"}],"related_material":{"record":[{"status":"public","id":"5564","relation":"popular_science"},{"id":"26","status":"public","relation":"dissertation_contains"}]},"publication":"eLife","citation":{"ama":"Steinrück M, Guet CC. Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection. <i>eLife</i>. 2017;6. doi:<a href=\"https://doi.org/10.7554/eLife.25100\">10.7554/eLife.25100</a>","short":"M. Steinrück, C.C. Guet, ELife 6 (2017).","ieee":"M. Steinrück and C. C. Guet, “Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection,” <i>eLife</i>, vol. 6. eLife Sciences Publications, 2017.","ista":"Steinrück M, Guet CC. 2017. Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection. eLife. 6, e25100.","chicago":"Steinrück, Magdalena, and Calin C Guet. “Complex Chromosomal Neighborhood Effects Determine the Adaptive Potential of a Gene under Selection.” <i>ELife</i>. eLife Sciences Publications, 2017. <a href=\"https://doi.org/10.7554/eLife.25100\">https://doi.org/10.7554/eLife.25100</a>.","apa":"Steinrück, M., &#38; Guet, C. C. (2017). Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.25100\">https://doi.org/10.7554/eLife.25100</a>","mla":"Steinrück, Magdalena, and Calin C. Guet. “Complex Chromosomal Neighborhood Effects Determine the Adaptive Potential of a Gene under Selection.” <i>ELife</i>, vol. 6, e25100, eLife Sciences Publications, 2017, doi:<a href=\"https://doi.org/10.7554/eLife.25100\">10.7554/eLife.25100</a>."},"intvolume":"         6"},{"author":[{"full_name":"Barone, Vanessa","first_name":"Vanessa","id":"419EECCC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2676-3367","last_name":"Barone"},{"last_name":"Lang","first_name":"Moritz","full_name":"Lang, Moritz","id":"29E0800A-F248-11E8-B48F-1D18A9856A87"},{"id":"2B819732-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4761-5996","full_name":"Krens, Gabriel","first_name":"Gabriel","last_name":"Krens"},{"last_name":"Pradhan","first_name":"Saurabh","full_name":"Pradhan, Saurabh"},{"full_name":"Shamipour, Shayan","first_name":"Shayan","id":"40B34FE2-F248-11E8-B48F-1D18A9856A87","last_name":"Shamipour"},{"last_name":"Sako","id":"3BED66BE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6453-8075","first_name":"Keisuke","full_name":"Sako, Keisuke"},{"id":"2F74BCDE-F248-11E8-B48F-1D18A9856A87","first_name":"Mateusz K","full_name":"Sikora, Mateusz K","last_name":"Sikora"},{"last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","first_name":"Calin C","full_name":"Guet, Calin C"},{"last_name":"Heisenberg","first_name":"Carl-Philipp J","full_name":"Heisenberg, Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0912-4566"}],"abstract":[{"lang":"eng","text":"Cell-cell contact formation constitutes an essential step in evolution, leading to the differentiation of specialized cell types. However, remarkably little is known about whether and how the interplay between contact formation and fate specification affects development. Here, we identify a positive feedback loop between cell-cell contact duration, morphogen signaling, and mesendoderm cell-fate specification during zebrafish gastrulation. We show that long-lasting cell-cell contacts enhance the competence of prechordal plate (ppl) progenitor cells to respond to Nodal signaling, required for ppl cell-fate specification. We further show that Nodal signaling promotes ppl cell-cell contact duration, generating a positive feedback loop between ppl cell-cell contact duration and cell-fate specification. Finally, by combining mathematical modeling and experimentation, we show that this feedback determines whether anterior axial mesendoderm cells become ppl or, instead, turn into endoderm. Thus, the interdependent activities of cell-cell signaling and contact formation control fate diversification within the developing embryo."}],"external_id":{"isi":["000413443700011"]},"oa_version":"None","publication_identifier":{"issn":["1534-5807"]},"publication_status":"published","date_created":"2018-12-11T11:48:13Z","doi":"10.1016/j.devcel.2017.09.014","article_processing_charge":"No","citation":{"ista":"Barone V, Lang M, Krens G, Pradhan S, Shamipour S, Sako K, Sikora MK, Guet CC, Heisenberg C-PJ. 2017. An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate. Developmental Cell. 43(2), 198–211.","ieee":"V. Barone <i>et al.</i>, “An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate,” <i>Developmental Cell</i>, vol. 43, no. 2. Cell Press, pp. 198–211, 2017.","chicago":"Barone, Vanessa, Moritz Lang, Gabriel Krens, Saurabh Pradhan, Shayan Shamipour, Keisuke Sako, Mateusz K Sikora, Calin C Guet, and Carl-Philipp J Heisenberg. “An Effective Feedback Loop between Cell-Cell Contact Duration and Morphogen Signaling Determines Cell Fate.” <i>Developmental Cell</i>. Cell Press, 2017. <a href=\"https://doi.org/10.1016/j.devcel.2017.09.014\">https://doi.org/10.1016/j.devcel.2017.09.014</a>.","short":"V. Barone, M. Lang, G. Krens, S. Pradhan, S. Shamipour, K. Sako, M.K. Sikora, C.C. Guet, C.-P.J. Heisenberg, Developmental Cell 43 (2017) 198–211.","ama":"Barone V, Lang M, Krens G, et al. An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate. <i>Developmental Cell</i>. 2017;43(2):198-211. doi:<a href=\"https://doi.org/10.1016/j.devcel.2017.09.014\">10.1016/j.devcel.2017.09.014</a>","mla":"Barone, Vanessa, et al. “An Effective Feedback Loop between Cell-Cell Contact Duration and Morphogen Signaling Determines Cell Fate.” <i>Developmental Cell</i>, vol. 43, no. 2, Cell Press, 2017, pp. 198–211, doi:<a href=\"https://doi.org/10.1016/j.devcel.2017.09.014\">10.1016/j.devcel.2017.09.014</a>.","apa":"Barone, V., Lang, M., Krens, G., Pradhan, S., Shamipour, S., Sako, K., … Heisenberg, C.-P. J. (2017). An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate. <i>Developmental Cell</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.devcel.2017.09.014\">https://doi.org/10.1016/j.devcel.2017.09.014</a>"},"intvolume":"        43","publication":"Developmental Cell","corr_author":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","isi":1,"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"961"},{"relation":"dissertation_contains","status":"public","id":"8350"}]},"language":[{"iso":"eng"}],"volume":43,"month":"10","date_published":"2017-10-23T00:00:00Z","_id":"735","publisher":"Cell Press","title":"An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate","quality_controlled":"1","year":"2017","publist_id":"6934","department":[{"_id":"CaHe"},{"_id":"CaGu"},{"_id":"GaTk"}],"type":"journal_article","status":"public","issue":"2","page":"198 - 211","ec_funded":1,"project":[{"_id":"25681D80-B435-11E9-9278-68D0E5697425","name":"International IST Postdoc Fellowship Programme","grant_number":"291734","call_identifier":"FP7"},{"call_identifier":"FWF","grant_number":"I2058","name":"Cell segregation in gastrulation: the role of cell fate specification","_id":"252DD2A6-B435-11E9-9278-68D0E5697425"}],"fulldoi":"https://doi.org/10.1016/j.devcel.2017.09.014","day":"23","date_updated":"2026-10-16T22:30:22Z","scopus_import":"1"},{"publist_id":"7004","department":[{"_id":"ToBo"},{"_id":"NiBa"},{"_id":"CaGu"}],"pubrep_id":"894","file":[{"checksum":"9143c290fa6458ed2563bff4b295554a","file_id":"5117","date_created":"2018-12-12T10:15:01Z","access_level":"open_access","file_size":3775716,"creator":"system","file_name":"IST-2017-894-v1+1_journal.pcbi.1005609.pdf","relation":"main_file","content_type":"application/pdf","date_updated":"2020-07-14T12:47:46Z"}],"year":"2017","quality_controlled":"1","ddc":["576"],"scopus_import":"1","fulldoi":"https://doi.org/10.1371/journal.pcbi.1005609","date_updated":"2026-10-16T22:31:03Z","day":"18","issue":"7","ec_funded":1,"project":[{"_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"618091","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation"}],"has_accepted_license":"1","status":"public","type":"journal_article","related_material":{"record":[{"relation":"research_data","id":"9849","status":"public"},{"relation":"research_data","status":"public","id":"9850"},{"relation":"research_data","status":"public","id":"9851"},{"relation":"research_data","status":"public","id":"9852"},{"id":"6263","status":"public","relation":"dissertation_contains"}]},"language":[{"iso":"eng"}],"corr_author":"1","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","isi":1,"intvolume":"        13","citation":{"ama":"Lukacisinova M, Novak S, Paixao T. Stress induced mutagenesis: Stress diversity facilitates the persistence of mutator genes. <i>PLoS Computational Biology</i>. 2017;13(7). doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1005609\">10.1371/journal.pcbi.1005609</a>","short":"M. Lukacisinova, S. Novak, T. Paixao, PLoS Computational Biology 13 (2017).","ieee":"M. Lukacisinova, S. Novak, and T. Paixao, “Stress induced mutagenesis: Stress diversity facilitates the persistence of mutator genes,” <i>PLoS Computational Biology</i>, vol. 13, no. 7. Public Library of Science, 2017.","chicago":"Lukacisinova, Marta, Sebastian Novak, and Tiago Paixao. “Stress Induced Mutagenesis: Stress Diversity Facilitates the Persistence of Mutator Genes.” <i>PLoS Computational Biology</i>. Public Library of Science, 2017. <a href=\"https://doi.org/10.1371/journal.pcbi.1005609\">https://doi.org/10.1371/journal.pcbi.1005609</a>.","ista":"Lukacisinova M, Novak S, Paixao T. 2017. Stress induced mutagenesis: Stress diversity facilitates the persistence of mutator genes. PLoS Computational Biology. 13(7), e1005609.","apa":"Lukacisinova, M., Novak, S., &#38; Paixao, T. (2017). Stress induced mutagenesis: Stress diversity facilitates the persistence of mutator genes. <i>PLoS Computational Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pcbi.1005609\">https://doi.org/10.1371/journal.pcbi.1005609</a>","mla":"Lukacisinova, Marta, et al. “Stress Induced Mutagenesis: Stress Diversity Facilitates the Persistence of Mutator Genes.” <i>PLoS Computational Biology</i>, vol. 13, no. 7, e1005609, Public Library of Science, 2017, doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1005609\">10.1371/journal.pcbi.1005609</a>."},"publication":"PLoS Computational Biology","publication_status":"published","date_created":"2018-12-11T11:47:58Z","doi":"10.1371/journal.pcbi.1005609","article_processing_charge":"No","publication_identifier":{"issn":["1553-734X"]},"oa_version":"Published Version","article_number":"e1005609","file_date_updated":"2020-07-14T12:47:46Z","abstract":[{"lang":"eng","text":"Mutator strains are expected to evolve when the availability and effect of beneficial mutations are high enough to counteract the disadvantage from deleterious mutations that will inevitably accumulate. As the population becomes more adapted to its environment, both availability and effect of beneficial mutations necessarily decrease and mutation rates are predicted to decrease. It has been shown that certain molecular mechanisms can lead to increased mutation rates when the organism finds itself in a stressful environment. While this may be a correlated response to other functions, it could also be an adaptive mechanism, raising mutation rates only when it is most advantageous. Here, we use a mathematical model to investigate the plausibility of the adaptive hypothesis. We show that such a mechanism can be mantained if the population is subjected to diverse stresses. By simulating various antibiotic treatment schemes, we find that combination treatments can reduce the effectiveness of second-order selection on stress-induced mutagenesis. We discuss the implications of our results to strategies of antibiotic therapy."}],"author":[{"id":"4342E402-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2519-8004","first_name":"Marta","full_name":"Lukacisinova, Marta","last_name":"Lukacisinova"},{"last_name":"Novak","orcid":"0000-0002-2519-824X","id":"461468AE-F248-11E8-B48F-1D18A9856A87","full_name":"Novak, Sebastian","first_name":"Sebastian"},{"id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2361-3953","full_name":"Paixao, Tiago","first_name":"Tiago","last_name":"Paixao"}],"external_id":{"isi":["000406619800014"]},"title":"Stress induced mutagenesis: Stress diversity facilitates the persistence of mutator genes","article_type":"original","publisher":"Public Library of Science","_id":"696","date_published":"2017-07-18T00:00:00Z","oa":1,"volume":13,"month":"07","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"}}]