[{"publication":"eLife","citation":{"ama":"Lagator M, Sarikas S, Acar H, Bollback JP, Guet CC. Regulatory network structure determines patterns of intermolecular epistasis. eLife. 2017;6. doi:10.7554/eLife.28921","ieee":"M. Lagator, S. Sarikas, H. Acar, J. P. Bollback, and C. C. Guet, “Regulatory network structure determines patterns of intermolecular epistasis,” eLife, vol. 6. eLife Sciences Publications, 2017.","apa":"Lagator, M., Sarikas, S., Acar, H., Bollback, J. P., & Guet, C. C. (2017). Regulatory network structure determines patterns of intermolecular epistasis. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.28921","ista":"Lagator M, Sarikas S, Acar H, Bollback JP, Guet CC. 2017. Regulatory network structure determines patterns of intermolecular epistasis. eLife. 6, e28921.","short":"M. Lagator, S. Sarikas, H. Acar, J.P. Bollback, C.C. Guet, ELife 6 (2017).","mla":"Lagator, Mato, et al. “Regulatory Network Structure Determines Patterns of Intermolecular Epistasis.” ELife, vol. 6, e28921, eLife Sciences Publications, 2017, doi:10.7554/eLife.28921.","chicago":"Lagator, Mato, Srdjan Sarikas, Hande Acar, Jonathan P Bollback, and Calin C Guet. “Regulatory Network Structure Determines Patterns of Intermolecular Epistasis.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.28921."},"date_published":"2017-11-13T00:00:00Z","scopus_import":1,"day":"13","has_accepted_license":"1","title":"Regulatory network structure determines patterns of intermolecular epistasis","ddc":["576"],"status":"public","intvolume":" 6","_id":"570","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Published Version","file":[{"date_updated":"2020-07-14T12:47:10Z","date_created":"2018-12-12T10:14:42Z","checksum":"273ab17f33305e4eaafd911ff88e7c5b","relation":"main_file","file_id":"5096","content_type":"application/pdf","file_size":8453470,"creator":"system","file_name":"IST-2017-918-v1+1_elife-28921-figures-v3.pdf","access_level":"open_access"},{"access_level":"open_access","file_name":"IST-2017-918-v1+2_elife-28921-v3.pdf","creator":"system","content_type":"application/pdf","file_size":1953221,"file_id":"5097","relation":"main_file","checksum":"b433f90576c7be597cd43367946f8e7f","date_created":"2018-12-12T10:14:43Z","date_updated":"2020-07-14T12:47:10Z"}],"pubrep_id":"918","type":"journal_article","abstract":[{"text":"Most phenotypes are determined by molecular systems composed of specifically interacting molecules. However, unlike for individual components, little is known about the distributions of mutational effects of molecular systems as a whole. We ask how the distribution of mutational effects of a transcriptional regulatory system differs from the distributions of its components, by first independently, and then simultaneously, mutating a transcription factor and the associated promoter it represses. We find that the system distribution exhibits increased phenotypic variation compared to individual component distributions - an effect arising from intermolecular epistasis between the transcription factor and its DNA-binding site. In large part, this epistasis can be qualitatively attributed to the structure of the transcriptional regulatory system and could therefore be a common feature in prokaryotes. Counter-intuitively, intermolecular epistasis can alleviate the constraints of individual components, thereby increasing phenotypic variation that selection could act on and facilitating adaptive evolution. ","lang":"eng"}],"quality_controlled":"1","project":[{"grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme"},{"_id":"2578D616-B435-11E9-9278-68D0E5697425","grant_number":"648440","name":"Selective Barriers to Horizontal Gene Transfer","call_identifier":"H2020"}],"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"language":[{"iso":"eng"}],"doi":"10.7554/eLife.28921","month":"11","publication_identifier":{"issn":["2050084X"]},"publication_status":"published","publisher":"eLife Sciences Publications","department":[{"_id":"CaGu"},{"_id":"JoBo"},{"_id":"NiBa"}],"year":"2017","date_created":"2018-12-11T11:47:14Z","date_updated":"2021-01-12T08:03:15Z","volume":6,"author":[{"id":"345D25EC-F248-11E8-B48F-1D18A9856A87","last_name":"Lagator","first_name":"Mato","full_name":"Lagator, Mato"},{"full_name":"Sarikas, Srdjan","id":"35F0286E-F248-11E8-B48F-1D18A9856A87","first_name":"Srdjan","last_name":"Sarikas"},{"id":"2DDF136A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1986-9753","first_name":"Hande","last_name":"Acar","full_name":"Acar, Hande"},{"full_name":"Bollback, Jonathan P","last_name":"Bollback","first_name":"Jonathan P","orcid":"0000-0002-4624-4612","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet"}],"article_number":"e28921","file_date_updated":"2020-07-14T12:47:10Z","ec_funded":1,"publist_id":"7244"},{"author":[{"full_name":"Chait, Remy P","id":"3464AE84-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0876-3187","first_name":"Remy P","last_name":"Chait"},{"first_name":"Jakob","last_name":"Ruess","id":"4A245D00-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1615-3282","full_name":"Ruess, Jakob"},{"full_name":"Bergmiller, Tobias","orcid":"0000-0001-5396-4346","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","last_name":"Bergmiller","first_name":"Tobias"},{"full_name":"Tkacik, Gasper","last_name":"Tkacik","first_name":"Gasper","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C","full_name":"Guet, Calin C"}],"volume":8,"date_updated":"2021-01-12T08:06:15Z","date_created":"2018-12-11T11:47:30Z","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).","year":"2017","publisher":"Nature Publishing Group","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publication_status":"published","publist_id":"7191","ec_funded":1,"file_date_updated":"2020-07-14T12:47:20Z","article_number":"1535","doi":"10.1038/s41467-017-01683-1","language":[{"iso":"eng"}],"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"project":[{"call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734"},{"_id":"254E9036-B435-11E9-9278-68D0E5697425","grant_number":"P28844-B27","name":"Biophysics of information processing in gene regulation","call_identifier":"FWF"}],"quality_controlled":"1","publication_identifier":{"issn":["20411723"]},"month":"12","pubrep_id":"911","oa_version":"Published Version","file":[{"date_updated":"2020-07-14T12:47:20Z","date_created":"2018-12-12T10:16:05Z","checksum":"44bb5d0229926c23a9955d9fe0f9723f","relation":"main_file","file_id":"5190","file_size":1951699,"content_type":"application/pdf","creator":"system","file_name":"IST-2017-911-v1+1_s41467-017-01683-1.pdf","access_level":"open_access"}],"_id":"613","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","intvolume":" 8","title":"Shaping bacterial population behavior through computer interfaced control of individual cells","ddc":["576","579"],"status":"public","issue":"1","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."}],"type":"journal_article","date_published":"2017-12-01T00:00:00Z","citation":{"ama":"Chait RP, Ruess J, Bergmiller T, Tkačik G, Guet CC. Shaping bacterial population behavior through computer interfaced control of individual cells. Nature Communications. 2017;8(1). doi:10.1038/s41467-017-01683-1","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.","apa":"Chait, R. P., Ruess, J., Bergmiller, T., Tkačik, G., & Guet, C. C. (2017). Shaping bacterial population behavior through computer interfaced control of individual cells. Nature Communications. Nature Publishing Group. https://doi.org/10.1038/s41467-017-01683-1","ieee":"R. P. Chait, J. Ruess, T. Bergmiller, G. Tkačik, and C. C. Guet, “Shaping bacterial population behavior through computer interfaced control of individual cells,” Nature Communications, vol. 8, no. 1. Nature Publishing Group, 2017.","mla":"Chait, Remy P., et al. “Shaping Bacterial Population Behavior through Computer Interfaced Control of Individual Cells.” Nature Communications, vol. 8, no. 1, 1535, Nature Publishing Group, 2017, doi:10.1038/s41467-017-01683-1.","short":"R.P. Chait, J. Ruess, T. Bergmiller, G. Tkačik, C.C. Guet, Nature Communications 8 (2017).","chicago":"Chait, Remy P, Jakob Ruess, Tobias Bergmiller, Gašper Tkačik, and Calin C Guet. “Shaping Bacterial Population Behavior through Computer Interfaced Control of Individual Cells.” Nature Communications. Nature Publishing Group, 2017. https://doi.org/10.1038/s41467-017-01683-1."},"publication":"Nature Communications","has_accepted_license":"1","article_processing_charge":"Yes (in subscription journal)","day":"01","scopus_import":1},{"abstract":[{"lang":"eng","text":"Bacteria adapt to adverse environmental conditions by altering gene expression patterns. Recently, a novel stress adaptation mechanism has been described that allows Escherichia coli to alter gene expression at the post-transcriptional level. The key player in this regulatory pathway is the endoribonuclease MazF, the toxin component of the toxin-antitoxin module mazEF that is triggered by various stressful conditions. In general, MazF degrades the majority of transcripts by cleaving at ACA sites, which results in the retardation of bacterial growth. Furthermore, MazF can process a small subset of mRNAs and render them leaderless by removing their ribosome binding site. MazF concomitantly modifies ribosomes, making them selective for the translation of leaderless mRNAs. In this study, we employed fluorescent reporter-systems to investigate mazEF expression during stressful conditions, and to infer consequences of the mRNA processing mediated by MazF on gene expression at the single-cell level. Our results suggest that mazEF transcription is maintained at low levels in single cells encountering adverse conditions, such as antibiotic stress or amino acid starvation. Moreover, using the grcA mRNA as a model for MazF-mediated mRNA processing, we found that MazF activation promotes heterogeneity in the grcA reporter expression, resulting in a subpopulation of cells with increased levels of GrcA reporter protein."}],"issue":"9","type":"journal_article","file":[{"date_updated":"2020-07-14T12:47:24Z","date_created":"2018-12-12T10:11:51Z","checksum":"3d79ae6b6eabc90b0eaaed82ff3493b0","file_id":"4908","relation":"main_file","creator":"system","file_size":682064,"content_type":"application/pdf","file_name":"IST-2017-909-v1+1_peerj-3830.pdf","access_level":"open_access"}],"oa_version":"Published Version","pubrep_id":"909","status":"public","ddc":["579"],"title":"MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations","intvolume":" 2017","_id":"624","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","day":"21","has_accepted_license":"1","scopus_import":1,"date_published":"2017-09-21T00:00:00Z","publication":"PeerJ","citation":{"chicago":"Nikolic, Nela, Zrinka Didara, and Isabella Moll. “MazF Activation Promotes Translational Heterogeneity of the GrcA MRNA in Escherichia Coli Populations.” PeerJ. PeerJ, 2017. https://doi.org/10.7717/peerj.3830.","mla":"Nikolic, Nela, et al. “MazF Activation Promotes Translational Heterogeneity of the GrcA MRNA in Escherichia Coli Populations.” PeerJ, vol. 2017, no. 9, 3830, PeerJ, 2017, doi:10.7717/peerj.3830.","short":"N. Nikolic, Z. Didara, I. Moll, PeerJ 2017 (2017).","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.","ieee":"N. Nikolic, Z. Didara, and I. Moll, “MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations,” PeerJ, vol. 2017, no. 9. PeerJ, 2017.","apa":"Nikolic, N., Didara, Z., & Moll, I. (2017). MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations. PeerJ. PeerJ. https://doi.org/10.7717/peerj.3830","ama":"Nikolic N, Didara Z, Moll I. MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations. PeerJ. 2017;2017(9). doi:10.7717/peerj.3830"},"file_date_updated":"2020-07-14T12:47:24Z","publist_id":"7172","article_number":"3830","date_created":"2018-12-11T11:47:33Z","date_updated":"2021-01-12T08:06:48Z","volume":2017,"author":[{"first_name":"Nela","last_name":"Nikolic","id":"42D9CABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9068-6090","full_name":"Nikolic, Nela"},{"full_name":"Didara, Zrinka","first_name":"Zrinka","last_name":"Didara"},{"first_name":"Isabella","last_name":"Moll","full_name":"Moll, Isabella"}],"publication_status":"published","department":[{"_id":"CaGu"}],"publisher":"PeerJ","year":"2017","acknowledgement":"Austrian Science Fund (FWF): M1697, P22249; Swiss National Science Foundation (SNF): 145706; European Commission;FWF Special Research Program: RNA-REG F43","month":"09","publication_identifier":{"issn":["21678359"]},"language":[{"iso":"eng"}],"doi":"10.7717/peerj.3830","quality_controlled":"1","oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"}},{"article_number":"e23136","publist_id":"7082","file_date_updated":"2020-07-14T12:47:33Z","department":[{"_id":"CaGu"}],"publisher":"eLife Sciences Publications","publication_status":"published","year":"2017","volume":6,"date_created":"2018-12-11T11:47:44Z","date_updated":"2021-01-12T08:07:55Z","author":[{"full_name":"Renault, Thibaud","first_name":"Thibaud","last_name":"Renault"},{"last_name":"Abraham","first_name":"Anthony","full_name":"Abraham, Anthony"},{"last_name":"Bergmiller","first_name":"Tobias","orcid":"0000-0001-5396-4346","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","full_name":"Bergmiller, Tobias"},{"first_name":"Guillaume","last_name":"Paradis","full_name":"Paradis, Guillaume"},{"full_name":"Rainville, Simon","last_name":"Rainville","first_name":"Simon"},{"first_name":"Emmanuelle","last_name":"Charpentier","full_name":"Charpentier, Emmanuelle"},{"full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C"},{"full_name":"Tu, Yuhai","first_name":"Yuhai","last_name":"Tu"},{"first_name":"Keiichi","last_name":"Namba","full_name":"Namba, Keiichi"},{"last_name":"Keener","first_name":"James","full_name":"Keener, James"},{"last_name":"Minamino","first_name":"Tohru","full_name":"Minamino, Tohru"},{"full_name":"Erhardt, Marc","last_name":"Erhardt","first_name":"Marc"}],"publication_identifier":{"issn":["2050084X"]},"month":"03","quality_controlled":"1","oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"language":[{"iso":"eng"}],"doi":"10.7554/eLife.23136","type":"journal_article","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."}],"intvolume":" 6","status":"public","ddc":["579"],"title":"Bacterial flagella grow through an injection diffusion mechanism","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"655","oa_version":"Published Version","file":[{"file_id":"4716","relation":"main_file","checksum":"39e1c3e82ddac83a30422fa72fa1a383","date_updated":"2020-07-14T12:47:33Z","date_created":"2018-12-12T10:08:53Z","access_level":"open_access","file_name":"IST-2017-904-v1+1_elife-23136-v2.pdf","creator":"system","content_type":"application/pdf","file_size":5520359},{"checksum":"a6d542253028f52e00aa29739ddffe8f","date_created":"2018-12-12T10:08:54Z","date_updated":"2020-07-14T12:47:33Z","relation":"main_file","file_id":"4717","file_size":11242920,"content_type":"application/pdf","creator":"system","access_level":"open_access","file_name":"IST-2017-904-v1+2_elife-23136-figures-v2.pdf"}],"pubrep_id":"904","scopus_import":1,"has_accepted_license":"1","day":"06","citation":{"mla":"Renault, Thibaud, et al. “Bacterial Flagella Grow through an Injection Diffusion Mechanism.” ELife, vol. 6, e23136, eLife Sciences Publications, 2017, doi:10.7554/eLife.23136.","short":"T. Renault, A. Abraham, T. Bergmiller, G. Paradis, S. Rainville, E. Charpentier, C.C. Guet, Y. Tu, K. Namba, J. Keener, T. Minamino, M. Erhardt, ELife 6 (2017).","chicago":"Renault, Thibaud, Anthony Abraham, Tobias Bergmiller, Guillaume Paradis, Simon Rainville, Emmanuelle Charpentier, Calin C Guet, et al. “Bacterial Flagella Grow through an Injection Diffusion Mechanism.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.23136.","ama":"Renault T, Abraham A, Bergmiller T, et al. Bacterial flagella grow through an injection diffusion mechanism. eLife. 2017;6. doi:10.7554/eLife.23136","ista":"Renault T, Abraham A, Bergmiller T, Paradis G, Rainville S, Charpentier E, Guet CC, Tu Y, Namba K, Keener J, Minamino T, Erhardt M. 2017. Bacterial flagella grow through an injection diffusion mechanism. eLife. 6, e23136.","apa":"Renault, T., Abraham, A., Bergmiller, T., Paradis, G., Rainville, S., Charpentier, E., … Erhardt, M. (2017). Bacterial flagella grow through an injection diffusion mechanism. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.23136","ieee":"T. Renault et al., “Bacterial flagella grow through an injection diffusion mechanism,” eLife, vol. 6. eLife Sciences Publications, 2017."},"publication":"eLife","date_published":"2017-03-06T00:00:00Z"},{"pubrep_id":"959","oa_version":"Published Version","file":[{"relation":"main_file","file_id":"5088","date_created":"2018-12-12T10:14:35Z","date_updated":"2020-07-14T12:46:46Z","checksum":"22426d9382f21554bad5fa5967afcfd0","file_name":"IST-2018-959-v1+1_2017_Nikolic_Cell-to-cell.pdf","access_level":"open_access","file_size":1308475,"content_type":"application/pdf","creator":"system"}],"_id":"541","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":" 13","title":"Cell-to-cell variation and specialization in sugar metabolism in clonal bacterial populations","ddc":["576","579"],"status":"public","issue":"12","abstract":[{"lang":"eng","text":"While we have good understanding of bacterial metabolism at the population level, we know little about the metabolic behavior of individual cells: do single cells in clonal populations sometimes specialize on different metabolic pathways? Such metabolic specialization could be driven by stochastic gene expression and could provide individual cells with growth benefits of specialization. We measured the degree of phenotypic specialization in two parallel metabolic pathways, the assimilation of glucose and arabinose. We grew Escherichia coli in chemostats, and used isotope-labeled sugars in combination with nanometer-scale secondary ion mass spectrometry and mathematical modeling to quantify sugar assimilation at the single-cell level. We found large variation in metabolic activities between single cells, both in absolute assimilation and in the degree to which individual cells specialize in the assimilation of different sugars. Analysis of transcriptional reporters indicated that this variation was at least partially based on cell-to-cell variation in gene expression. Metabolic differences between cells in clonal populations could potentially reduce metabolic incompatibilities between different pathways, and increase the rate at which parallel reactions can be performed."}],"type":"journal_article","date_published":"2017-12-18T00:00:00Z","citation":{"chicago":"Nikolic, Nela, Frank Schreiber, Alma Dal Co, Daniel Kiviet, Tobias Bergmiller, Sten Littmann, Marcel Kuypers, and Martin Ackermann. “Cell-to-Cell Variation and Specialization in Sugar Metabolism in Clonal Bacterial Populations.” PLoS Genetics. Public Library of Science, 2017. https://doi.org/10.1371/journal.pgen.1007122.","short":"N. Nikolic, F. Schreiber, A. Dal Co, D. Kiviet, T. Bergmiller, S. Littmann, M. Kuypers, M. Ackermann, PLoS Genetics 13 (2017).","mla":"Nikolic, Nela, et al. “Cell-to-Cell Variation and Specialization in Sugar Metabolism in Clonal Bacterial Populations.” PLoS Genetics, vol. 13, no. 12, e1007122, Public Library of Science, 2017, doi:10.1371/journal.pgen.1007122.","ieee":"N. Nikolic et al., “Cell-to-cell variation and specialization in sugar metabolism in clonal bacterial populations,” PLoS Genetics, vol. 13, no. 12. Public Library of Science, 2017.","apa":"Nikolic, N., Schreiber, F., Dal Co, A., Kiviet, D., Bergmiller, T., Littmann, S., … Ackermann, M. (2017). Cell-to-cell variation and specialization in sugar metabolism in clonal bacterial populations. PLoS Genetics. Public Library of Science. https://doi.org/10.1371/journal.pgen.1007122","ista":"Nikolic N, Schreiber F, Dal Co A, Kiviet D, Bergmiller T, Littmann S, Kuypers M, Ackermann M. 2017. Cell-to-cell variation and specialization in sugar metabolism in clonal bacterial populations. PLoS Genetics. 13(12), e1007122.","ama":"Nikolic N, Schreiber F, Dal Co A, et al. Cell-to-cell variation and specialization in sugar metabolism in clonal bacterial populations. 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M.P. is a recipient of a DOC Fellowship of the Austrian Academy of Science at the Institute of Science and Technology Austria.","pmid":1,"date_created":"2018-12-11T11:47:11Z","date_updated":"2023-09-07T11:59:32Z","volume":13,"author":[{"id":"4569785E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7460-7479","first_name":"Maros","last_name":"Pleska","full_name":"Pleska, Maros"},{"full_name":"Guet, Calin C","first_name":"Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052"}],"related_material":{"record":[{"id":"9847","status":"public","relation":"research_data"},{"relation":"dissertation_contains","status":"public","id":"202"}]},"month":"12","publication_identifier":{"issn":["1744-9561"]},"quality_controlled":"1","project":[{"grant_number":"RGY0079/2011","_id":"251BCBEC-B435-11E9-9278-68D0E5697425","name":"Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification Systems (HFSP Young investigators' grant)"},{"name":"Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level (DOC Fellowship)","_id":"251D65D8-B435-11E9-9278-68D0E5697425","grant_number":"24210"}],"main_file_link":[{"url":"https://doi.org/10.1098/rsbl.2017.0646","open_access":"1"}],"external_id":{"pmid":["29237814"]},"oa":1,"language":[{"iso":"eng"}],"doi":"10.1098/rsbl.2017.0646","type":"journal_article","abstract":[{"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.","lang":"eng"}],"issue":"12","status":"public","title":"Effects of mutations in phage restriction sites during escape from restriction–modification","intvolume":" 13","_id":"561","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Published Version","scopus_import":"1","day":"01","article_processing_charge":"No","article_type":"original","publication":"Biology Letters","citation":{"mla":"Pleska, Maros, and Calin C. Guet. “Effects of Mutations in Phage Restriction Sites during Escape from Restriction–Modification.” Biology Letters, vol. 13, no. 12, 20170646, The Royal Society, 2017, doi:10.1098/rsbl.2017.0646.","short":"M. Pleska, C.C. Guet, Biology Letters 13 (2017).","chicago":"Pleska, Maros, and Calin C Guet. “Effects of Mutations in Phage Restriction Sites during Escape from Restriction–Modification.” Biology Letters. The Royal Society, 2017. https://doi.org/10.1098/rsbl.2017.0646.","ama":"Pleska M, Guet CC. Effects of mutations in phage restriction sites during escape from restriction–modification. Biology Letters. 2017;13(12). doi:10.1098/rsbl.2017.0646","ista":"Pleska M, Guet CC. 2017. Effects of mutations in phage restriction sites during escape from restriction–modification. Biology Letters. 13(12), 20170646.","apa":"Pleska, M., & Guet, C. C. (2017). Effects of mutations in phage restriction sites during escape from restriction–modification. Biology Letters. The Royal Society. https://doi.org/10.1098/rsbl.2017.0646","ieee":"M. Pleska and C. C. Guet, “Effects of mutations in phage restriction sites during escape from restriction–modification,” Biology Letters, vol. 13, no. 12. The Royal Society, 2017."},"date_published":"2017-12-01T00:00:00Z"},{"citation":{"ama":"Pleska M. Biology of restriction-modification systems at the single-cell and population level. 2017. doi:10.15479/AT:ISTA:th_916","ista":"Pleska M. 2017. Biology of restriction-modification systems at the single-cell and population level. Institute of Science and Technology Austria.","ieee":"M. Pleska, “Biology of restriction-modification systems at the single-cell and population level,” Institute of Science and Technology Austria, 2017.","apa":"Pleska, M. (2017). Biology of restriction-modification systems at the single-cell and population level. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_916","mla":"Pleska, Maros. Biology of Restriction-Modification Systems at the Single-Cell and Population Level. Institute of Science and Technology Austria, 2017, doi:10.15479/AT:ISTA:th_916.","short":"M. Pleska, Biology of Restriction-Modification Systems at the Single-Cell and Population Level, Institute of Science and Technology Austria, 2017.","chicago":"Pleska, Maros. “Biology of Restriction-Modification Systems at the Single-Cell and Population Level.” Institute of Science and Technology Austria, 2017. https://doi.org/10.15479/AT:ISTA:th_916."},"page":"126","date_published":"2017-10-01T00:00:00Z","article_processing_charge":"No","has_accepted_license":"1","day":"01","_id":"202","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","title":"Biology of restriction-modification systems at the single-cell and population level","status":"public","ddc":["576","579"],"pubrep_id":"916","file":[{"relation":"main_file","file_id":"4710","date_created":"2018-12-12T10:08:48Z","date_updated":"2020-07-14T12:45:24Z","checksum":"33cfb59674e91f82e3738396d3fb3776","file_name":"IST-2018-916-v1+3_2017_Pleska_Maros_Thesis.pdf","access_level":"open_access","file_size":18569590,"content_type":"application/pdf","creator":"system"},{"access_level":"closed","file_name":"2017_Pleska_Maros_Thesis.docx","creator":"dernst","file_size":2801649,"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_id":"6204","relation":"source_file","checksum":"dcc239968decb233e7f98cf1083d8c26","date_updated":"2020-07-14T12:45:24Z","date_created":"2019-04-05T08:33:14Z"}],"oa_version":"Published Version","type":"dissertation","alternative_title":["ISTA Thesis"],"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."}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"project":[{"name":"Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level (DOC Fellowship)","grant_number":"24210","_id":"251D65D8-B435-11E9-9278-68D0E5697425"}],"doi":"10.15479/AT:ISTA:th_916","language":[{"iso":"eng"}],"degree_awarded":"PhD","supervisor":[{"full_name":"Guet, Calin C","last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"}],"publication_identifier":{"issn":["2663-337X"]},"month":"10","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","publisher":"Institute of Science and Technology Austria","department":[{"_id":"CaGu"}],"publication_status":"published","related_material":{"record":[{"id":"1243","status":"public","relation":"part_of_dissertation"},{"status":"public","relation":"part_of_dissertation","id":"561"},{"relation":"part_of_dissertation","status":"public","id":"457"}]},"author":[{"full_name":"Pleska, Maros","first_name":"Maros","last_name":"Pleska","id":"4569785E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7460-7479"}],"date_updated":"2023-09-15T12:04:56Z","date_created":"2018-12-11T11:45:10Z","publist_id":"7711","file_date_updated":"2020-07-14T12:45:24Z"},{"volume":54,"date_updated":"2023-09-20T11:06:03Z","date_created":"2018-12-11T11:51:32Z","related_material":{"record":[{"id":"1835","status":"public","relation":"earlier_version"}]},"author":[{"full_name":"Giacobbe, Mirco","orcid":"0000-0001-8180-0904","id":"3444EA5E-F248-11E8-B48F-1D18A9856A87","last_name":"Giacobbe","first_name":"Mirco"},{"full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C"},{"id":"335E5684-F248-11E8-B48F-1D18A9856A87","first_name":"Ashutosh","last_name":"Gupta","full_name":"Gupta, Ashutosh"},{"id":"40876CD8-F248-11E8-B48F-1D18A9856A87","orcid":"0000−0002−2985−7724","first_name":"Thomas A","last_name":"Henzinger","full_name":"Henzinger, Thomas A"},{"first_name":"Tiago","last_name":"Paixao","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2361-3953","full_name":"Paixao, Tiago"},{"first_name":"Tatjana","last_name":"Petrov","id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9041-0905","full_name":"Petrov, Tatjana"}],"department":[{"_id":"ToHe"},{"_id":"CaGu"},{"_id":"NiBa"}],"publisher":"Springer","publication_status":"published","year":"2017","ec_funded":1,"publist_id":"5898","file_date_updated":"2020-07-14T12:44:46Z","language":[{"iso":"eng"}],"doi":"10.1007/s00236-016-0278-x","project":[{"grant_number":"267989","_id":"25EE3708-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"Quantitative Reactive Modeling"},{"name":"Rigorous Systems Engineering","call_identifier":"FWF","grant_number":"S 11407_N23","_id":"25832EC2-B435-11E9-9278-68D0E5697425"},{"name":"The Wittgenstein Prize","call_identifier":"FWF","grant_number":"Z211","_id":"25F42A32-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FP7","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","grant_number":"618091"},{"grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425","name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7"},{"_id":"25B07788-B435-11E9-9278-68D0E5697425","grant_number":"250152","name":"Limits to selection in biology and in evolutionary computation","call_identifier":"FP7"}],"isi":1,"quality_controlled":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"external_id":{"isi":["000414343200003"]},"publication_identifier":{"issn":["00015903"]},"month":"12","file":[{"date_created":"2019-01-17T15:57:29Z","date_updated":"2020-07-14T12:44:46Z","checksum":"4e661d9135d7f8c342e8e258dee76f3e","file_id":"5841","relation":"main_file","creator":"dernst","file_size":755241,"content_type":"application/pdf","file_name":"2017_ActaInformatica_Giacobbe.pdf","access_level":"open_access"}],"oa_version":"Published Version","pubrep_id":"649","intvolume":" 54","title":"Model checking the evolution of gene regulatory networks","status":"public","ddc":["006","576"],"_id":"1351","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","issue":"8","abstract":[{"lang":"eng","text":"The behaviour of gene regulatory networks (GRNs) is typically analysed using simulation-based statistical testing-like methods. In this paper, we demonstrate that we can replace this approach by a formal verification-like method that gives higher assurance and scalability. We focus on Wagner’s weighted GRN model with varying weights, which is used in evolutionary biology. In the model, weight parameters represent the gene interaction strength that may change due to genetic mutations. For a property of interest, we synthesise the constraints over the parameter space that represent the set of GRNs satisfying the property. We experimentally show that our parameter synthesis procedure computes the mutational robustness of GRNs—an important problem of interest in evolutionary biology—more efficiently than the classical simulation method. We specify the property in linear temporal logic. We employ symbolic bounded model checking and SMT solving to compute the space of GRNs that satisfy the property, which amounts to synthesizing a set of linear constraints on the weights."}],"type":"journal_article","date_published":"2017-12-01T00:00:00Z","page":"765 - 787","citation":{"ieee":"M. Giacobbe, C. C. Guet, A. Gupta, T. A. Henzinger, T. Paixao, and T. Petrov, “Model checking the evolution of gene regulatory networks,” Acta Informatica, vol. 54, no. 8. Springer, pp. 765–787, 2017.","apa":"Giacobbe, M., Guet, C. C., Gupta, A., Henzinger, T. A., Paixao, T., & Petrov, T. (2017). Model checking the evolution of gene regulatory networks. Acta Informatica. Springer. https://doi.org/10.1007/s00236-016-0278-x","ista":"Giacobbe M, Guet CC, Gupta A, Henzinger TA, Paixao T, Petrov T. 2017. Model checking the evolution of gene regulatory networks. Acta Informatica. 54(8), 765–787.","ama":"Giacobbe M, Guet CC, Gupta A, Henzinger TA, Paixao T, Petrov T. Model checking the evolution of gene regulatory networks. Acta Informatica. 2017;54(8):765-787. doi:10.1007/s00236-016-0278-x","chicago":"Giacobbe, Mirco, Calin C Guet, Ashutosh Gupta, Thomas A Henzinger, Tiago Paixao, and Tatjana Petrov. “Model Checking the Evolution of Gene Regulatory Networks.” Acta Informatica. Springer, 2017. https://doi.org/10.1007/s00236-016-0278-x.","short":"M. Giacobbe, C.C. Guet, A. Gupta, T.A. Henzinger, T. Paixao, T. Petrov, Acta Informatica 54 (2017) 765–787.","mla":"Giacobbe, Mirco, et al. “Model Checking the Evolution of Gene Regulatory Networks.” Acta Informatica, vol. 54, no. 8, Springer, 2017, pp. 765–87, doi:10.1007/s00236-016-0278-x."},"publication":"Acta Informatica","has_accepted_license":"1","article_processing_charge":"No","day":"01","scopus_import":"1"},{"scopus_import":"1","article_processing_charge":"No","has_accepted_license":"1","day":"01","page":"681 - 713","citation":{"short":"T. Paixao, J. Pérez Heredia, D. Sudholt, B. Trubenova, Algorithmica 78 (2017) 681–713.","mla":"Paixao, Tiago, et al. “Towards a Runtime Comparison of Natural and Artificial Evolution.” Algorithmica, vol. 78, no. 2, Springer, 2017, pp. 681–713, doi:10.1007/s00453-016-0212-1.","chicago":"Paixao, Tiago, Jorge Pérez Heredia, Dirk Sudholt, and Barbora Trubenova. “Towards a Runtime Comparison of Natural and Artificial Evolution.” Algorithmica. Springer, 2017. https://doi.org/10.1007/s00453-016-0212-1.","ama":"Paixao T, Pérez Heredia J, Sudholt D, Trubenova B. Towards a runtime comparison of natural and artificial evolution. Algorithmica. 2017;78(2):681-713. doi:10.1007/s00453-016-0212-1","ieee":"T. Paixao, J. Pérez Heredia, D. Sudholt, and B. Trubenova, “Towards a runtime comparison of natural and artificial evolution,” Algorithmica, vol. 78, no. 2. Springer, pp. 681–713, 2017.","apa":"Paixao, T., Pérez Heredia, J., Sudholt, D., & Trubenova, B. (2017). Towards a runtime comparison of natural and artificial evolution. Algorithmica. Springer. https://doi.org/10.1007/s00453-016-0212-1","ista":"Paixao T, Pérez Heredia J, Sudholt D, Trubenova B. 2017. Towards a runtime comparison of natural and artificial evolution. Algorithmica. 78(2), 681–713."},"publication":"Algorithmica","date_published":"2017-06-01T00:00:00Z","type":"journal_article","issue":"2","abstract":[{"text":"Evolutionary algorithms (EAs) form a popular optimisation paradigm inspired by natural evolution. In recent years the field of evolutionary computation has developed a rigorous analytical theory to analyse the runtimes of EAs on many illustrative problems. Here we apply this theory to a simple model of natural evolution. In the Strong Selection Weak Mutation (SSWM) evolutionary regime the time between occurrences of new mutations is much longer than the time it takes for a mutated genotype to take over the population. In this situation, the population only contains copies of one genotype and evolution can be modelled as a stochastic process evolving one genotype by means of mutation and selection between the resident and the mutated genotype. The probability of accepting the mutated genotype then depends on the change in fitness. We study this process, SSWM, from an algorithmic perspective, quantifying its expected optimisation time for various parameters and investigating differences to a similar evolutionary algorithm, the well-known (1+1) EA. We show that SSWM can have a moderate advantage over the (1+1) EA at crossing fitness valleys and study an example where SSWM outperforms the (1+1) EA by taking advantage of information on the fitness gradient.","lang":"eng"}],"intvolume":" 78","title":"Towards a runtime comparison of natural and artificial evolution","ddc":["576"],"status":"public","_id":"1336","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa_version":"Published Version","file":[{"content_type":"application/pdf","file_size":710206,"creator":"system","file_name":"IST-2016-658-v1+1_s00453-016-0212-1.pdf","access_level":"open_access","date_created":"2018-12-12T10:10:19Z","date_updated":"2020-07-14T12:44:44Z","checksum":"7873f665a0c598ac747c908f34cb14b9","relation":"main_file","file_id":"4805"}],"pubrep_id":"658","publication_identifier":{"issn":["01784617"]},"month":"06","project":[{"grant_number":"618091","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation"}],"isi":1,"quality_controlled":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000400379500013"]},"oa":1,"language":[{"iso":"eng"}],"doi":"10.1007/s00453-016-0212-1","publist_id":"5931","ec_funded":1,"file_date_updated":"2020-07-14T12:44:44Z","department":[{"_id":"NiBa"},{"_id":"CaGu"}],"publisher":"Springer","publication_status":"published","year":"2017","volume":78,"date_created":"2018-12-11T11:51:27Z","date_updated":"2023-09-20T11:14:42Z","author":[{"full_name":"Paixao, Tiago","last_name":"Paixao","first_name":"Tiago","orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Pérez Heredia","first_name":"Jorge","full_name":"Pérez Heredia, Jorge"},{"full_name":"Sudholt, Dirk","first_name":"Dirk","last_name":"Sudholt"},{"first_name":"Barbora","last_name":"Trubenova","id":"42302D54-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6873-2967","full_name":"Trubenova, Barbora"}]},{"month":"04","publication_identifier":{"issn":[" 0950382X"]},"language":[{"iso":"eng"}],"doi":"10.1111/mmi.13597","quality_controlled":"1","isi":1,"external_id":{"isi":["000398059200002"]},"publist_id":"6294","date_created":"2018-12-11T11:50:03Z","date_updated":"2023-09-20T11:48:43Z","volume":104,"author":[{"full_name":"Fang, Chong","first_name":"Chong","last_name":"Fang"},{"id":"3ABC5BA6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1391-8377","first_name":"Anna A","last_name":"Nagy-Staron","full_name":"Nagy-Staron, Anna A"},{"full_name":"Grafe, Martin","first_name":"Martin","last_name":"Grafe"},{"last_name":"Heermann","first_name":"Ralf","full_name":"Heermann, Ralf"},{"full_name":"Jung, Kirsten","first_name":"Kirsten","last_name":"Jung"},{"last_name":"Gebhard","first_name":"Susanne","full_name":"Gebhard, Susanne"},{"last_name":"Mascher","first_name":"Thorsten","full_name":"Mascher, Thorsten"}],"publication_status":"published","publisher":"Wiley-Blackwell","department":[{"_id":"CaGu"}],"year":"2017","day":"01","article_processing_charge":"No","scopus_import":"1","date_published":"2017-04-01T00:00:00Z","page":"16 - 31","publication":"Molecular Microbiology","citation":{"ama":"Fang C, Nagy-Staron AA, Grafe M, et al. Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis. Molecular Microbiology. 2017;104(1):16-31. doi:10.1111/mmi.13597","ista":"Fang C, Nagy-Staron AA, Grafe M, Heermann R, Jung K, Gebhard S, Mascher T. 2017. Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis. Molecular Microbiology. 104(1), 16–31.","apa":"Fang, C., Nagy-Staron, A. A., Grafe, M., Heermann, R., Jung, K., Gebhard, S., & Mascher, T. (2017). Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis. Molecular Microbiology. Wiley-Blackwell. https://doi.org/10.1111/mmi.13597","ieee":"C. Fang et al., “Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis,” Molecular Microbiology, vol. 104, no. 1. Wiley-Blackwell, pp. 16–31, 2017.","mla":"Fang, Chong, et al. “Insulation and Wiring Specificity of BceR like Response Regulators and Their Target Promoters in Bacillus Subtilis.” Molecular Microbiology, vol. 104, no. 1, Wiley-Blackwell, 2017, pp. 16–31, doi:10.1111/mmi.13597.","short":"C. Fang, A.A. Nagy-Staron, M. Grafe, R. Heermann, K. Jung, S. Gebhard, T. Mascher, Molecular Microbiology 104 (2017) 16–31.","chicago":"Fang, Chong, Anna A Nagy-Staron, Martin Grafe, Ralf Heermann, Kirsten Jung, Susanne Gebhard, and Thorsten Mascher. “Insulation and Wiring Specificity of BceR like Response Regulators and Their Target Promoters in Bacillus Subtilis.” Molecular Microbiology. Wiley-Blackwell, 2017. https://doi.org/10.1111/mmi.13597."},"abstract":[{"lang":"eng","text":"BceRS and PsdRS are paralogous two-component systems in Bacillus subtilis controlling the response to antimicrobial peptides. In the presence of extracellular bacitracin and nisin, respectively, the two response regulators (RRs) bind their target promoters, PbceA or PpsdA, resulting in a strong up-regulation of target gene expression and ultimately antibiotic resistance. Despite high sequence similarity between the RRs BceR and PsdR and their known binding sites, no cross-regulation has been observed between them. We therefore investigated the specificity determinants of PbceA and PpsdA that ensure the insulation of these two paralogous pathways at the RR–promoter interface. In vivo and in vitro analyses demonstrate that the regulatory regions within these two promoters contain three important elements: in addition to the known (main) binding site, we identified a linker region and a secondary binding site that are crucial for functionality. Initial binding to the high-affinity, low-specificity main binding site is a prerequisite for the subsequent highly specific binding of a second RR dimer to the low-affinity secondary binding site. In addition to this hierarchical cooperative binding, discrimination requires a competition of the two RRs for their respective binding site mediated by only slight differences in binding affinities."}],"issue":"1","type":"journal_article","oa_version":"None","title":"Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis","status":"public","intvolume":" 104","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"1084"},{"isi":1,"quality_controlled":"1","project":[{"_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","grant_number":"618091","call_identifier":"FP7","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation"},{"name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425"},{"grant_number":"648440","_id":"2578D616-B435-11E9-9278-68D0E5697425","name":"Selective Barriers to Horizontal Gene Transfer","call_identifier":"H2020"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000404024800001"]},"oa":1,"language":[{"iso":"eng"}],"doi":"10.7554/eLife.25192","month":"05","publication_identifier":{"issn":["2050084X"]},"publication_status":"published","department":[{"_id":"CaGu"},{"_id":"NiBa"},{"_id":"JoBo"}],"publisher":"eLife Sciences Publications","year":"2017","date_created":"2018-12-11T11:49:23Z","date_updated":"2023-09-22T10:01:17Z","volume":6,"author":[{"full_name":"Lagator, Mato","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","first_name":"Mato","last_name":"Lagator"},{"full_name":"Paixao, Tiago","orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","last_name":"Paixao","first_name":"Tiago"},{"orcid":"0000-0002-8548-5240","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","last_name":"Barton","first_name":"Nicholas H","full_name":"Barton, Nicholas H"},{"last_name":"Bollback","first_name":"Jonathan P","orcid":"0000-0002-4624-4612","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","full_name":"Bollback, Jonathan P"},{"orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C","full_name":"Guet, Calin C"}],"article_number":"e25192","file_date_updated":"2020-07-14T12:48:16Z","publist_id":"6460","ec_funded":1,"publication":"eLife","citation":{"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,” eLife, vol. 6. eLife Sciences Publications, 2017.","apa":"Lagator, M., Paixao, T., Barton, N. H., Bollback, J. P., & Guet, C. C. (2017). On the mechanistic nature of epistasis in a canonical cis-regulatory element. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.25192","ama":"Lagator M, Paixao T, Barton NH, Bollback JP, Guet CC. On the mechanistic nature of epistasis in a canonical cis-regulatory element. eLife. 2017;6. doi:10.7554/eLife.25192","chicago":"Lagator, Mato, Tiago Paixao, Nicholas H Barton, Jonathan P Bollback, and Calin C Guet. “On the Mechanistic Nature of Epistasis in a Canonical Cis-Regulatory Element.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.25192.","mla":"Lagator, Mato, et al. “On the Mechanistic Nature of Epistasis in a Canonical Cis-Regulatory Element.” ELife, vol. 6, e25192, eLife Sciences Publications, 2017, doi:10.7554/eLife.25192.","short":"M. Lagator, T. Paixao, N.H. Barton, J.P. Bollback, C.C. Guet, ELife 6 (2017)."},"date_published":"2017-05-18T00:00:00Z","scopus_import":"1","day":"18","has_accepted_license":"1","article_processing_charge":"Yes","status":"public","title":"On the mechanistic nature of epistasis in a canonical cis-regulatory element","ddc":["576"],"intvolume":" 6","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"954","oa_version":"Published Version","file":[{"file_size":2441529,"content_type":"application/pdf","creator":"system","access_level":"open_access","file_name":"IST-2017-841-v1+1_elife-25192-v2.pdf","checksum":"59cdd4400fb41280122d414fea971546","date_created":"2018-12-12T10:17:49Z","date_updated":"2020-07-14T12:48:16Z","relation":"main_file","file_id":"5306"},{"file_name":"IST-2017-841-v1+2_elife-25192-figures-v2.pdf","access_level":"open_access","creator":"system","file_size":3752660,"content_type":"application/pdf","file_id":"5307","relation":"main_file","date_updated":"2020-07-14T12:48:16Z","date_created":"2018-12-12T10:17:50Z","checksum":"b69024880558b858eb8c5d47a92b6377"}],"pubrep_id":"841","type":"journal_article","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"}]},{"date_published":"2017-06-01T00:00:00Z","citation":{"chicago":"Lang, Moritz, and Eduardo Sontag. “Zeros of Nonlinear Systems with Input Invariances.” Automatica. International Federation of Automatic Control, 2017. https://doi.org/10.1016/j.automatica.2017.03.030.","mla":"Lang, Moritz, and Eduardo Sontag. “Zeros of Nonlinear Systems with Input Invariances.” Automatica, vol. 81C, International Federation of Automatic Control, 2017, pp. 46–55, doi:10.1016/j.automatica.2017.03.030.","short":"M. Lang, E. Sontag, Automatica 81C (2017) 46–55.","ista":"Lang M, Sontag E. 2017. Zeros of nonlinear systems with input invariances. Automatica. 81C, 46–55.","ieee":"M. Lang and E. Sontag, “Zeros of nonlinear systems with input invariances,” Automatica, vol. 81C. International Federation of Automatic Control, pp. 46–55, 2017.","apa":"Lang, M., & Sontag, E. (2017). Zeros of nonlinear systems with input invariances. Automatica. International Federation of Automatic Control. https://doi.org/10.1016/j.automatica.2017.03.030","ama":"Lang M, Sontag E. Zeros of nonlinear systems with input invariances. Automatica. 2017;81C:46-55. doi:10.1016/j.automatica.2017.03.030"},"publication":"Automatica","page":"46 - 55","has_accepted_license":"1","article_processing_charge":"Yes (in subscription journal)","day":"01","scopus_import":"1","pubrep_id":"813","oa_version":"Published Version","file":[{"date_created":"2018-12-12T10:11:29Z","date_updated":"2018-12-12T10:11:29Z","relation":"main_file","file_id":"4884","file_size":1401954,"content_type":"application/pdf","creator":"system","access_level":"open_access","file_name":"IST-2017-813-v1+1_ZerosOfNonlinearSystems.pdf"}],"_id":"1007","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Zeros of nonlinear systems with input invariances","ddc":["000"],"status":"public","abstract":[{"text":"A nonlinear system possesses an invariance with respect to a set of transformations if its output dynamics remain invariant when transforming the input, and adjusting the initial condition accordingly. Most research has focused on invariances with respect to time-independent pointwise transformations like translational-invariance (u(t) -> u(t) + p, p in R) or scale-invariance (u(t) -> pu(t), p in R>0). In this article, we introduce the concept of s0-invariances with respect to continuous input transformations exponentially growing/decaying over time. We show that s0-invariant systems not only encompass linear time-invariant (LTI) systems with transfer functions having an irreducible zero at s0 in R, but also that the input/output relationship of nonlinear s0-invariant systems possesses properties well known from their linear counterparts. Furthermore, we extend the concept of s0-invariances to second- and higher-order s0-invariances, corresponding to invariances with respect to transformations of the time-derivatives of the input, and encompassing LTI systems with zeros of multiplicity two or higher. Finally, we show that nth-order 0-invariant systems realize – under mild conditions – nth-order nonlinear differential operators: when excited by an input of a characteristic functional form, the system’s output converges to a constant value only depending on the nth (nonlinear) derivative of the input.","lang":"eng"}],"type":"journal_article","doi":"10.1016/j.automatica.2017.03.030","language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"external_id":{"isi":["000403513900006"]},"project":[{"call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme","grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425"}],"quality_controlled":"1","isi":1,"publication_identifier":{"issn":["0005-1098"]},"month":"06","author":[{"full_name":"Lang, Moritz","id":"29E0800A-F248-11E8-B48F-1D18A9856A87","last_name":"Lang","first_name":"Moritz"},{"full_name":"Sontag, Eduardo","last_name":"Sontag","first_name":"Eduardo"}],"volume":"81C","date_updated":"2023-10-17T08:51:18Z","date_created":"2018-12-11T11:49:39Z","year":"2017","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publisher":"International Federation of Automatic Control","publication_status":"published","ec_funded":1,"publist_id":"6391","file_date_updated":"2018-12-12T10:11:29Z"},{"date_published":"2017-04-11T00:00:00Z","doi":"10.15479/AT:ISTA:65","citation":{"ista":"Steinrück M, Guet CC. 2017. Fastq files for ‘Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection’, Institute of Science and Technology Austria, 10.15479/AT:ISTA:65.","ieee":"M. Steinrück and C. C. Guet, “Fastq files for ‘Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection.’” Institute of Science and Technology Austria, 2017.","apa":"Steinrück, M., & Guet, C. C. (2017). Fastq files for “Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:65","ama":"Steinrück M, Guet CC. 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Guet, (2017)."},"tmp":{"short":"CC0 (1.0)","image":"/images/cc_0.png","legal_code_url":"https://creativecommons.org/publicdomain/zero/1.0/legalcode","name":"Creative Commons Public Domain Dedication (CC0 1.0)"},"oa":1,"month":"04","day":"11","article_processing_charge":"No","has_accepted_license":"1","author":[{"full_name":"Steinrück, Magdalena","id":"2C023F40-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1229-9719","first_name":"Magdalena","last_name":"Steinrück"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet","full_name":"Guet, Calin C"}],"related_material":{"record":[{"status":"public","relation":"research_paper","id":"704"}]},"date_updated":"2024-02-21T13:47:28Z","date_created":"2018-12-12T12:31:33Z","file":[{"checksum":"31a0c01d022721073241a23d192cc37e","date_created":"2018-12-12T13:03:18Z","date_updated":"2020-07-14T12:47:03Z","relation":"main_file","file_id":"5627","content_type":"application/zip","file_size":1225959109,"creator":"system","access_level":"open_access","file_name":"IST-2017-65-v1+1_D_anc_1.fastq.zip"},{"file_id":"5628","relation":"main_file","checksum":"d8f26f83ce7e7e45436121f9c6cd9b83","date_updated":"2020-07-14T12:47:03Z","date_created":"2018-12-12T13:03:30Z","access_level":"open_access","file_name":"IST-2017-65-v1+1_D_anc_2.fastq.zip","creator":"system","file_size":1422656107,"content_type":"application/zip"},{"checksum":"e07b99bcfe55b5f132ca03b8b48c8cbc","date_updated":"2020-07-14T12:47:03Z","date_created":"2018-12-12T13:03:33Z","file_id":"5629","relation":"main_file","creator":"system","content_type":"application/zip","file_size":565014975,"access_level":"open_access","file_name":"IST-2017-65-v1+2_D_A11_1.fastq.zip"},{"checksum":"eda86143d5f32d844b54f8530041e32b","date_updated":"2020-07-14T12:47:03Z","date_created":"2018-12-12T13:03:42Z","file_id":"5630","relation":"main_file","creator":"system","content_type":"application/zip","file_size":564490030,"access_level":"open_access","file_name":"IST-2017-65-v1+3_D_A11_2.fastq.zip"},{"file_name":"IST-2017-65-v1+4_D_C10_1.fastq.zip","access_level":"open_access","file_size":875430169,"content_type":"application/zip","creator":"system","relation":"main_file","file_id":"5631","date_created":"2018-12-12T13:03:46Z","date_updated":"2020-07-14T12:47:03Z","checksum":"906d44f950c1626d9b99f34fbf89cb12"},{"file_name":"IST-2017-65-v1+6_D_C08_2.fastq.zip","access_level":"open_access","creator":"system","content_type":"application/zip","file_size":638298201,"file_id":"5632","relation":"main_file","date_updated":"2020-07-14T12:47:03Z","date_created":"2018-12-12T13:03:54Z","checksum":"6ca14a032a79e0c787106bdf635725c9"},{"file_name":"IST-2017-65-v1+5_D_C10_2.fastq.zip","access_level":"open_access","creator":"system","content_type":"application/zip","file_size":894702866,"file_id":"5633","relation":"main_file","date_updated":"2020-07-14T12:47:03Z","date_created":"2018-12-12T13:04:01Z","checksum":"66ab16ddb5ba64b2e263ef746ebf2893"},{"access_level":"open_access","file_name":"IST-2017-65-v1+7_D_C08_1.fastq.zip","creator":"system","content_type":"application/zip","file_size":623648989,"file_id":"5634","relation":"main_file","checksum":"82607970174f8d37773b7d3acc712195","date_created":"2018-12-12T13:04:07Z","date_updated":"2020-07-14T12:47:03Z"},{"creator":"system","content_type":"application/zip","file_size":259359583,"access_level":"open_access","file_name":"IST-2017-65-v1+8_D_D08_1.fastq.zip","checksum":"225c30b243268c7dda9d6f8327933252","date_updated":"2020-07-14T12:47:03Z","date_created":"2018-12-12T13:04:11Z","file_id":"5635","relation":"main_file"}],"oa_version":"Published Version","_id":"5564","year":"2017","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","ddc":["576"],"title":"Fastq files for \"Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection\"","department":[{"_id":"CaGu"}],"publisher":"Institute of Science and Technology Austria","abstract":[{"text":"Compressed Fastq files with whole-genome sequencing data of IS-wt strain D and clones from four evolved populations (A11, C08, C10, D08). Information on this data collection is available in the Methods Section of the primary publication.","lang":"eng"}],"file_date_updated":"2020-07-14T12:47:03Z","datarep_id":"65","type":"research_data"},{"_id":"5560","year":"2017","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["571"],"title":"Biased partitioning of the multi-drug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity","status":"public","department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"Bio"}],"publisher":"Institute of Science and Technology Austria","author":[{"full_name":"Bergmiller, Tobias","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5396-4346","first_name":"Tobias","last_name":"Bergmiller"},{"last_name":"Andersson","first_name":"Anna M","orcid":"0000-0003-2912-6769","id":"2B8A40DA-F248-11E8-B48F-1D18A9856A87","full_name":"Andersson, Anna M"},{"orcid":"0000-0003-3768-877X","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","last_name":"Tomasek","first_name":"Kathrin","full_name":"Tomasek, Kathrin"},{"last_name":"Balleza","first_name":"Enrique","full_name":"Balleza, Enrique"},{"first_name":"Daniel","last_name":"Kiviet","full_name":"Kiviet, Daniel"},{"full_name":"Hauschild, Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9843-3522","first_name":"Robert","last_name":"Hauschild"},{"last_name":"Tkacik","first_name":"Gasper","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkacik, Gasper"},{"full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet"}],"related_material":{"record":[{"id":"665","relation":"research_paper","status":"public"}]},"date_updated":"2024-02-21T13:49:00Z","date_created":"2018-12-12T12:31:32Z","file":[{"date_updated":"2020-07-14T12:47:03Z","date_created":"2018-12-12T13:02:38Z","checksum":"d77859af757ac8025c50c7b12b52eaf3","file_id":"5603","relation":"main_file","creator":"system","file_size":6773204,"content_type":"application/zip","file_name":"IST-2017-53-v1+1_Data_MDE.zip","access_level":"open_access"}],"oa_version":"Published Version","datarep_id":"53","type":"research_data","abstract":[{"text":"This repository contains the data collected for the manuscript \"Biased partitioning of the multi-drug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity\".\r\nThe data is compressed into a single archive. Within the archive, different folders correspond to figures of the main text and the SI of the related publication.\r\nData is saved as plain text, with each folder containing a separate readme file describing the format. Typically, the data is from fluorescence microscopy measurements of single cells growing in a microfluidic \"mother machine\" device, and consists of relevant values (primarily arbitrary unit or normalized fluorescence measurements, and division times / growth rates) after raw microscopy images have been processed, segmented, and their features extracted, as described in the methods section of the related publication.","lang":"eng"}],"file_date_updated":"2020-07-14T12:47:03Z","tmp":{"short":"CC0 (1.0)","image":"/images/cc_0.png","legal_code_url":"https://creativecommons.org/publicdomain/zero/1.0/legalcode","name":"Creative Commons Public Domain Dedication (CC0 1.0)"},"oa":1,"citation":{"ista":"Bergmiller T, Andersson AM, Tomasek K, Balleza E, Kiviet D, Hauschild R, Tkačik G, Guet CC. 2017. Biased partitioning of the multi-drug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity, Institute of Science and Technology Austria, 10.15479/AT:ISTA:53.","ieee":"T. Bergmiller et al., “Biased partitioning of the multi-drug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity.” Institute of Science and Technology Austria, 2017.","apa":"Bergmiller, T., Andersson, A. M., Tomasek, K., Balleza, E., Kiviet, D., Hauschild, R., … Guet, C. C. (2017). Biased partitioning of the multi-drug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:53","ama":"Bergmiller T, Andersson AM, Tomasek K, et al. Biased partitioning of the multi-drug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity. 2017. doi:10.15479/AT:ISTA:53","chicago":"Bergmiller, Tobias, Anna M Andersson, Kathrin Tomasek, Enrique Balleza, Daniel Kiviet, Robert Hauschild, Gašper Tkačik, and Calin C Guet. “Biased Partitioning of the Multi-Drug Efflux Pump AcrAB-TolC Underlies Long-Lived Phenotypic Heterogeneity.” Institute of Science and Technology Austria, 2017. https://doi.org/10.15479/AT:ISTA:53.","mla":"Bergmiller, Tobias, et al. Biased Partitioning of the Multi-Drug Efflux Pump AcrAB-TolC Underlies Long-Lived Phenotypic Heterogeneity. Institute of Science and Technology Austria, 2017, doi:10.15479/AT:ISTA:53.","short":"T. Bergmiller, A.M. Andersson, K. Tomasek, E. Balleza, D. Kiviet, R. Hauschild, G. Tkačik, C.C. Guet, (2017)."},"doi":"10.15479/AT:ISTA:53","date_published":"2017-03-10T00:00:00Z","keyword":["single cell microscopy","mother machine microfluidic device","AcrAB-TolC pump","multi-drug efflux","Escherichia coli"],"month":"03","day":"10","article_processing_charge":"No","has_accepted_license":"1"},{"project":[{"_id":"254E9036-B435-11E9-9278-68D0E5697425","grant_number":"P28844-B27","name":"Biophysics of information processing in gene regulation","call_identifier":"FWF"}],"quality_controlled":"1","doi":"10.1126/science.aaf4762","language":[{"iso":"eng"}],"publication_identifier":{"issn":["00368075"]},"month":"04","year":"2017","publisher":"American Association for the Advancement of Science","department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"Bio"}],"publication_status":"published","related_material":{"record":[{"relation":"popular_science","status":"public","id":"5560"}]},"author":[{"full_name":"Bergmiller, Tobias","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5396-4346","first_name":"Tobias","last_name":"Bergmiller"},{"orcid":"0000-0003-2912-6769","id":"2B8A40DA-F248-11E8-B48F-1D18A9856A87","last_name":"Andersson","first_name":"Anna M","full_name":"Andersson, Anna M"},{"first_name":"Kathrin","last_name":"Tomasek","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3768-877X","full_name":"Tomasek, Kathrin"},{"full_name":"Balleza, Enrique","first_name":"Enrique","last_name":"Balleza"},{"last_name":"Kiviet","first_name":"Daniel","full_name":"Kiviet, Daniel"},{"id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9843-3522","first_name":"Robert","last_name":"Hauschild","full_name":"Hauschild, Robert"},{"full_name":"Tkacik, Gasper","last_name":"Tkacik","first_name":"Gasper","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C","full_name":"Guet, Calin C"}],"volume":356,"date_updated":"2024-02-21T13:49:00Z","date_created":"2018-12-11T11:47:48Z","publist_id":"7064","citation":{"chicago":"Bergmiller, Tobias, Anna M Andersson, Kathrin Tomasek, Enrique Balleza, Daniel Kiviet, Robert Hauschild, Gašper Tkačik, and Calin C Guet. “Biased Partitioning of the Multidrug Efflux Pump AcrAB TolC Underlies Long Lived Phenotypic Heterogeneity.” Science. American Association for the Advancement of Science, 2017. https://doi.org/10.1126/science.aaf4762.","mla":"Bergmiller, Tobias, et al. “Biased Partitioning of the Multidrug Efflux Pump AcrAB TolC Underlies Long Lived Phenotypic Heterogeneity.” Science, vol. 356, no. 6335, American Association for the Advancement of Science, 2017, pp. 311–15, doi:10.1126/science.aaf4762.","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.","apa":"Bergmiller, T., Andersson, A. M., Tomasek, K., Balleza, E., Kiviet, D., Hauschild, R., … Guet, C. C. (2017). Biased partitioning of the multidrug efflux pump AcrAB TolC underlies long lived phenotypic heterogeneity. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.aaf4762","ieee":"T. Bergmiller et al., “Biased partitioning of the multidrug efflux pump AcrAB TolC underlies long lived phenotypic heterogeneity,” Science, vol. 356, no. 6335. American Association for the Advancement of Science, pp. 311–315, 2017.","ama":"Bergmiller T, Andersson AM, Tomasek K, et al. Biased partitioning of the multidrug efflux pump AcrAB TolC underlies long lived phenotypic heterogeneity. Science. 2017;356(6335):311-315. doi:10.1126/science.aaf4762"},"publication":"Science","page":"311 - 315","article_type":"original","date_published":"2017-04-21T00:00:00Z","scopus_import":1,"article_processing_charge":"No","day":"21","_id":"665","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":" 356","status":"public","title":"Biased partitioning of the multidrug efflux pump AcrAB TolC underlies long lived phenotypic heterogeneity","oa_version":"None","type":"journal_article","issue":"6335","abstract":[{"text":"The molecular mechanisms underlying phenotypic variation in isogenic bacterial populations remain poorly understood.We report that AcrAB-TolC, the main multidrug efflux pump of Escherichia coli, exhibits a strong partitioning bias for old cell poles by a segregation mechanism that is mediated by ternary AcrAB-TolC complex formation. Mother cells inheriting old poles are phenotypically distinct and display increased drug efflux activity relative to daughters. Consequently, we find systematic and long-lived growth differences between mother and daughter cells in the presence of subinhibitory drug concentrations. A simple model for biased partitioning predicts a population structure of long-lived and highly heterogeneous phenotypes. This straightforward mechanism of generating sustained growth rate differences at subinhibitory antibiotic concentrations has implications for understanding the emergence of multidrug resistance in bacteria.","lang":"eng"}]},{"month":"03","publication_identifier":{"issn":["14337851"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"external_id":{"isi":["000398154000038"]},"quality_controlled":"1","isi":1,"project":[{"grant_number":"303564","_id":"25548C20-B435-11E9-9278-68D0E5697425","name":"Microbial Ion Channels for Synthetic Neurobiology","call_identifier":"FP7"},{"call_identifier":"FWF","name":"Molecular Drug Targets [do not use to be deleted]","_id":"26AA4EF2-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24"}],"doi":"10.1002/anie.201611998","language":[{"iso":"eng"}],"file_date_updated":"2019-01-18T09:39:55Z","ec_funded":1,"publist_id":"6362","year":"2017","acknowledgement":"This work was supported by a grant from the European Unions Seventh Framework Programme (CIG-303564). E.R. was supported by the graduate program MolecularDrugTargets (Austrian Science Fund (FWF), W1232) and a FemTech fellowship (Austrian Research Promotion Agency, 3580812)","publication_status":"published","department":[{"_id":"CaGu"},{"_id":"HaJa"}],"publisher":"Wiley-Blackwell","author":[{"full_name":"Kainrath, Stephanie","first_name":"Stephanie","last_name":"Kainrath","id":"32CFBA64-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Stadler, Manuela","first_name":"Manuela","last_name":"Stadler"},{"orcid":"0000-0002-7218-7738","id":"3FEE232A-F248-11E8-B48F-1D18A9856A87","last_name":"Gschaider-Reichhart","first_name":"Eva","full_name":"Gschaider-Reichhart, Eva"},{"first_name":"Martin","last_name":"Distel","full_name":"Distel, Martin"},{"last_name":"Janovjak","first_name":"Harald L","orcid":"0000-0002-8023-9315","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","full_name":"Janovjak, Harald L"}],"related_material":{"record":[{"id":"418","status":"public","relation":"dissertation_contains"},{"status":"public","relation":"part_of_dissertation","id":"7680"}]},"date_created":"2018-12-11T11:49:46Z","date_updated":"2024-03-28T23:30:13Z","volume":56,"scopus_import":"1","day":"20","article_processing_charge":"No","has_accepted_license":"1","publication":"Angewandte Chemie - International Edition","citation":{"short":"S. Kainrath, M. Stadler, E. Gschaider-Reichhart, M. Distel, H.L. Janovjak, Angewandte Chemie - International Edition 56 (2017) 4608–4611.","mla":"Kainrath, Stephanie, et al. “Green-Light-Induced Inactivation of Receptor Signaling Using Cobalamin-Binding Domains.” Angewandte Chemie - International Edition, vol. 56, no. 16, Wiley-Blackwell, 2017, pp. 4608–11, doi:10.1002/anie.201611998.","chicago":"Kainrath, Stephanie, Manuela Stadler, Eva Gschaider-Reichhart, Martin Distel, and Harald L Janovjak. “Green-Light-Induced Inactivation of Receptor Signaling Using Cobalamin-Binding Domains.” Angewandte Chemie - International Edition. Wiley-Blackwell, 2017. https://doi.org/10.1002/anie.201611998.","ama":"Kainrath S, Stadler M, Gschaider-Reichhart E, Distel M, Janovjak HL. Green-light-induced inactivation of receptor signaling using cobalamin-binding domains. Angewandte Chemie - International Edition. 2017;56(16):4608-4611. doi:10.1002/anie.201611998","ieee":"S. Kainrath, M. Stadler, E. Gschaider-Reichhart, M. Distel, and H. L. Janovjak, “Green-light-induced inactivation of receptor signaling using cobalamin-binding domains,” Angewandte Chemie - International Edition, vol. 56, no. 16. Wiley-Blackwell, pp. 4608–4611, 2017.","apa":"Kainrath, S., Stadler, M., Gschaider-Reichhart, E., Distel, M., & Janovjak, H. L. (2017). Green-light-induced inactivation of receptor signaling using cobalamin-binding domains. Angewandte Chemie - International Edition. Wiley-Blackwell. https://doi.org/10.1002/anie.201611998","ista":"Kainrath S, Stadler M, Gschaider-Reichhart E, Distel M, Janovjak HL. 2017. Green-light-induced inactivation of receptor signaling using cobalamin-binding domains. Angewandte Chemie - International Edition. 56(16), 4608–4611."},"page":"4608-4611","date_published":"2017-03-20T00:00:00Z","type":"journal_article","abstract":[{"lang":"eng","text":"Optogenetics and photopharmacology provide spatiotemporally precise control over protein interactions and protein function in cells and animals. Optogenetic methods that are sensitive to green light and can be used to break protein complexes are not broadly available but would enable multichromatic experiments with previously inaccessible biological targets. Herein, we repurposed cobalamin (vitamin B12) binding domains of bacterial CarH transcription factors for green-light-induced receptor dissociation. In cultured cells, we observed oligomerization-induced cell signaling for the fibroblast growth factor receptor 1 fused to cobalamin-binding domains in the dark that was rapidly eliminated upon illumination. In zebrafish embryos expressing fusion receptors, green light endowed control over aberrant fibroblast growth factor signaling during development. Green-light-induced domain dissociation and light-inactivated receptors will critically expand the optogenetic toolbox for control of biological processes."}],"issue":"16","_id":"1028","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","status":"public","title":"Green-light-induced inactivation of receptor signaling using cobalamin-binding domains","ddc":["540"],"intvolume":" 56","file":[{"file_id":"5845","relation":"main_file","success":1,"date_created":"2019-01-18T09:39:55Z","date_updated":"2019-01-18T09:39:55Z","access_level":"open_access","file_name":"2017_communications_Kainrath.pdf","creator":"dernst","content_type":"application/pdf","file_size":2614942}],"oa_version":"Published Version"},{"scopus_import":1,"day":"25","has_accepted_license":"1","publication":"eLife","citation":{"chicago":"Steinrück, Magdalena, and Calin C Guet. “Complex Chromosomal Neighborhood Effects Determine the Adaptive Potential of a Gene under Selection.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.25100.","mla":"Steinrück, Magdalena, and Calin C. Guet. “Complex Chromosomal Neighborhood Effects Determine the Adaptive Potential of a Gene under Selection.” ELife, vol. 6, e25100, eLife Sciences Publications, 2017, doi:10.7554/eLife.25100.","short":"M. Steinrück, C.C. Guet, ELife 6 (2017).","ista":"Steinrück M, Guet CC. 2017. Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection. eLife. 6, e25100.","apa":"Steinrück, M., & Guet, C. C. (2017). Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.25100","ieee":"M. Steinrück and C. C. Guet, “Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection,” eLife, vol. 6. eLife Sciences Publications, 2017.","ama":"Steinrück M, Guet CC. Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection. eLife. 2017;6. doi:10.7554/eLife.25100"},"date_published":"2017-07-25T00:00:00Z","type":"journal_article","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."}],"ddc":["576"],"status":"public","title":"Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection","intvolume":" 6","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"704","file":[{"access_level":"open_access","file_name":"IST-2017-890-v1+1_elife-25100-v1.pdf","content_type":"application/pdf","file_size":2092088,"creator":"system","relation":"main_file","file_id":"4975","checksum":"6b908b5db9f61f6820ebd7f8fa815571","date_created":"2018-12-12T10:12:54Z","date_updated":"2020-07-14T12:47:48Z"},{"date_created":"2018-12-12T10:12:55Z","date_updated":"2020-07-14T12:47:48Z","checksum":"ca21530389b720243552678125fdba35","file_id":"4976","relation":"main_file","creator":"system","content_type":"application/pdf","file_size":3428681,"file_name":"IST-2017-890-v1+2_elife-25100-figures-v1.pdf","access_level":"open_access"}],"oa_version":"Published Version","pubrep_id":"890","month":"07","publication_identifier":{"issn":["2050084X"]},"quality_controlled":"1","oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"language":[{"iso":"eng"}],"doi":"10.7554/eLife.25100","article_number":"e25100","file_date_updated":"2020-07-14T12:47:48Z","publist_id":"6990","publication_status":"published","department":[{"_id":"CaGu"}],"publisher":"eLife Sciences Publications","year":"2017","date_created":"2018-12-11T11:48:01Z","date_updated":"2024-03-28T23:30:28Z","volume":6,"author":[{"full_name":"Steinrück, Magdalena","orcid":"0000-0003-1229-9719","id":"2C023F40-F248-11E8-B48F-1D18A9856A87","last_name":"Steinrück","first_name":"Magdalena"},{"last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C"}],"related_material":{"record":[{"id":"5564","status":"public","relation":"popular_science"},{"status":"public","relation":"dissertation_contains","id":"26"}]}},{"publication_identifier":{"issn":["1553734X"]},"month":"07","language":[{"iso":"eng"}],"doi":"10.1371/journal.pcbi.1005609","project":[{"name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","call_identifier":"FP7","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","grant_number":"618091"}],"quality_controlled":"1","oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"ec_funded":1,"publist_id":"7004","file_date_updated":"2020-07-14T12:47:46Z","article_number":"e1005609","volume":13,"date_updated":"2024-03-28T23:30:28Z","date_created":"2018-12-11T11:47:58Z","related_material":{"record":[{"relation":"research_data","status":"public","id":"9849"},{"id":"9850","status":"public","relation":"research_data"},{"relation":"research_data","status":"public","id":"9851"},{"id":"9852","status":"public","relation":"research_data"},{"id":"6263","status":"public","relation":"dissertation_contains"}]},"author":[{"full_name":"Lukacisinova, Marta","id":"4342E402-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2519-8004","first_name":"Marta","last_name":"Lukacisinova"},{"full_name":"Novak, Sebastian","id":"461468AE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2519-824X","first_name":"Sebastian","last_name":"Novak"},{"full_name":"Paixao, Tiago","first_name":"Tiago","last_name":"Paixao","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2361-3953"}],"publisher":"Public Library of Science","department":[{"_id":"ToBo"},{"_id":"NiBa"},{"_id":"CaGu"}],"publication_status":"published","year":"2017","has_accepted_license":"1","day":"18","scopus_import":1,"date_published":"2017-07-18T00:00:00Z","article_type":"original","citation":{"mla":"Lukacisinova, Marta, et al. “Stress Induced Mutagenesis: Stress Diversity Facilitates the Persistence of Mutator Genes.” PLoS Computational Biology, vol. 13, no. 7, e1005609, Public Library of Science, 2017, doi:10.1371/journal.pcbi.1005609.","short":"M. Lukacisinova, S. Novak, T. Paixao, PLoS Computational Biology 13 (2017).","chicago":"Lukacisinova, Marta, Sebastian Novak, and Tiago Paixao. “Stress Induced Mutagenesis: Stress Diversity Facilitates the Persistence of Mutator Genes.” PLoS Computational Biology. Public Library of Science, 2017. https://doi.org/10.1371/journal.pcbi.1005609.","ama":"Lukacisinova M, Novak S, Paixao T. Stress induced mutagenesis: Stress diversity facilitates the persistence of mutator genes. PLoS Computational Biology. 2017;13(7). doi:10.1371/journal.pcbi.1005609","ista":"Lukacisinova M, Novak S, Paixao T. 2017. Stress induced mutagenesis: Stress diversity facilitates the persistence of mutator genes. PLoS Computational Biology. 13(7), e1005609.","ieee":"M. Lukacisinova, S. Novak, and T. Paixao, “Stress induced mutagenesis: Stress diversity facilitates the persistence of mutator genes,” PLoS Computational Biology, vol. 13, no. 7. Public Library of Science, 2017.","apa":"Lukacisinova, M., Novak, S., & Paixao, T. (2017). Stress induced mutagenesis: Stress diversity facilitates the persistence of mutator genes. PLoS Computational Biology. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1005609"},"publication":"PLoS Computational Biology","issue":"7","abstract":[{"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.","lang":"eng"}],"type":"journal_article","file":[{"checksum":"9143c290fa6458ed2563bff4b295554a","date_updated":"2020-07-14T12:47:46Z","date_created":"2018-12-12T10:15:01Z","file_id":"5117","relation":"main_file","creator":"system","content_type":"application/pdf","file_size":3775716,"access_level":"open_access","file_name":"IST-2017-894-v1+1_journal.pcbi.1005609.pdf"}],"oa_version":"Published Version","pubrep_id":"894","intvolume":" 13","status":"public","title":"Stress induced mutagenesis: Stress diversity facilitates the persistence of mutator genes","ddc":["576"],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"696"},{"publication":"Developmental Cell","citation":{"mla":"Barone, Vanessa, et al. “An Effective Feedback Loop between Cell-Cell Contact Duration and Morphogen Signaling Determines Cell Fate.” Developmental Cell, vol. 43, no. 2, Cell Press, 2017, pp. 198–211, doi:10.1016/j.devcel.2017.09.014.","short":"V. Barone, M. Lang, G. Krens, S. Pradhan, S. Shamipour, K. Sako, M.K. Sikora, C.C. Guet, C.-P.J. Heisenberg, Developmental Cell 43 (2017) 198–211.","chicago":"Barone, Vanessa, Moritz Lang, Gabriel Krens, Saurabh Pradhan, Shayan Shamipour, Keisuke Sako, Mateusz K Sikora, Calin C Guet, and Carl-Philipp J Heisenberg. “An Effective Feedback Loop between Cell-Cell Contact Duration and Morphogen Signaling Determines Cell Fate.” Developmental Cell. Cell Press, 2017. https://doi.org/10.1016/j.devcel.2017.09.014.","ama":"Barone V, Lang M, Krens G, et al. An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate. Developmental Cell. 2017;43(2):198-211. doi:10.1016/j.devcel.2017.09.014","ista":"Barone V, Lang M, Krens G, Pradhan S, Shamipour S, Sako K, Sikora MK, Guet CC, Heisenberg C-PJ. 2017. An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate. Developmental Cell. 43(2), 198–211.","ieee":"V. Barone et al., “An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate,” Developmental Cell, vol. 43, no. 2. Cell Press, pp. 198–211, 2017.","apa":"Barone, V., Lang, M., Krens, G., Pradhan, S., Shamipour, S., Sako, K., … Heisenberg, C.-P. J. (2017). An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate. Developmental Cell. Cell Press. https://doi.org/10.1016/j.devcel.2017.09.014"},"page":"198 - 211","date_published":"2017-10-23T00:00:00Z","scopus_import":"1","day":"23","article_processing_charge":"No","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"735","title":"An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate","status":"public","intvolume":" 43","oa_version":"None","type":"journal_article","abstract":[{"text":"Cell-cell contact formation constitutes an essential step in evolution, leading to the differentiation of specialized cell types. However, remarkably little is known about whether and how the interplay between contact formation and fate specification affects development. Here, we identify a positive feedback loop between cell-cell contact duration, morphogen signaling, and mesendoderm cell-fate specification during zebrafish gastrulation. We show that long-lasting cell-cell contacts enhance the competence of prechordal plate (ppl) progenitor cells to respond to Nodal signaling, required for ppl cell-fate specification. We further show that Nodal signaling promotes ppl cell-cell contact duration, generating a positive feedback loop between ppl cell-cell contact duration and cell-fate specification. Finally, by combining mathematical modeling and experimentation, we show that this feedback determines whether anterior axial mesendoderm cells become ppl or, instead, turn into endoderm. Thus, the interdependent activities of cell-cell signaling and contact formation control fate diversification within the developing embryo.","lang":"eng"}],"issue":"2","external_id":{"isi":["000413443700011"]},"quality_controlled":"1","isi":1,"project":[{"_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734","name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7"},{"name":"Cell segregation in gastrulation: the role of cell fate specification","call_identifier":"FWF","grant_number":"I2058","_id":"252DD2A6-B435-11E9-9278-68D0E5697425"}],"doi":"10.1016/j.devcel.2017.09.014","language":[{"iso":"eng"}],"month":"10","publication_identifier":{"issn":["15345807"]},"year":"2017","publication_status":"published","department":[{"_id":"CaHe"},{"_id":"CaGu"},{"_id":"GaTk"}],"publisher":"Cell Press","author":[{"first_name":"Vanessa","last_name":"Barone","id":"419EECCC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2676-3367","full_name":"Barone, Vanessa"},{"full_name":"Lang, Moritz","id":"29E0800A-F248-11E8-B48F-1D18A9856A87","last_name":"Lang","first_name":"Moritz"},{"full_name":"Krens, Gabriel","first_name":"Gabriel","last_name":"Krens","id":"2B819732-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4761-5996"},{"full_name":"Pradhan, Saurabh","last_name":"Pradhan","first_name":"Saurabh"},{"full_name":"Shamipour, Shayan","id":"40B34FE2-F248-11E8-B48F-1D18A9856A87","last_name":"Shamipour","first_name":"Shayan"},{"full_name":"Sako, Keisuke","last_name":"Sako","first_name":"Keisuke","orcid":"0000-0002-6453-8075","id":"3BED66BE-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Sikora","first_name":"Mateusz K","id":"2F74BCDE-F248-11E8-B48F-1D18A9856A87","full_name":"Sikora, Mateusz K"},{"last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C"},{"full_name":"Heisenberg, Carl-Philipp J","first_name":"Carl-Philipp J","last_name":"Heisenberg","id":"39427864-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0912-4566"}],"related_material":{"record":[{"id":"961","relation":"dissertation_contains","status":"public"},{"id":"8350","relation":"dissertation_contains","status":"public"}]},"date_created":"2018-12-11T11:48:13Z","date_updated":"2024-03-28T23:30:39Z","volume":43,"publist_id":"6934","ec_funded":1},{"_id":"1008","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","year":"2016","acknowledgement":"We thank Julio Polaina (Instituto de Agroqu ı ́ mica y Tecnolog ı ́ a de Alimentos, C.S.I.C., Paterna, Spain) for the gift of plasmid pMR4, Gregor W. Schmidt for provision of and support with the micro fl uidic device, Markus Du ̈ rr for the cell tracking R script, and Lukas Widmer for the script for MEIGO using “ parfor ” in MATLAB. We acknowledge the members of the Stelling group for discussions, comments, and support.","publisher":"American Chemical Society","department":[{"_id":"CaGu"}],"intvolume":" 5","status":"public","title":"An orthogonal permease–inducer–repressor feedback loop shows bistability","publication_status":"published","author":[{"first_name":"Robert","last_name":"Gnügge","full_name":"Gnügge, Robert"},{"last_name":"Dharmarajan","first_name":"Lekshmi","full_name":"Dharmarajan, Lekshmi"},{"id":"29E0800A-F248-11E8-B48F-1D18A9856A87","last_name":"Lang","first_name":"Moritz","full_name":"Lang, Moritz"},{"first_name":"Jörg","last_name":"Stelling","full_name":"Stelling, Jörg"}],"oa_version":"None","volume":5,"date_created":"2018-12-11T11:49:40Z","date_updated":"2021-01-12T06:47:37Z","type":"journal_article","issue":"10","publist_id":"6390","abstract":[{"lang":"eng","text":"Feedback loops in biological networks, among others, enable differentiation and cell cycle progression, and increase robustness in signal transduction. In natural networks, feedback loops are often complex and intertwined, making it challenging to identify which loops are mainly responsible for an observed behavior. However, minimal synthetic replicas could allow for such identification. Here, we engineered a synthetic permease-inducer-repressor system in Saccharomyces cerevisiae to analyze if a transport-mediated positive feedback loop could be a core mechanism for the switch-like behavior in the regulation of metabolic gene networks such as the S. cerevisiae GAL system or the Escherichia coli lac operon. We characterized the synthetic circuit using deterministic and stochastic mathematical models. Similar to its natural counterparts, our synthetic system shows bistable and hysteretic behavior, and the inducer concentration range for bistability as well as the switching rates between the two stable states depend on the repressor concentration. Our results indicate that a generic permease–inducer–repressor circuit with a single feedback loop is sufficient to explain the experimentally observed bistable behavior of the natural systems. We anticipate that the approach of reimplementing natural systems with orthogonal parts to identify crucial network components is applicable to other natural systems such as signaling pathways."}],"citation":{"ieee":"R. Gnügge, L. Dharmarajan, M. Lang, and J. Stelling, “An orthogonal permease–inducer–repressor feedback loop shows bistability,” ACS Synthetic Biology, vol. 5, no. 10. American Chemical Society, pp. 1098–1107, 2016.","apa":"Gnügge, R., Dharmarajan, L., Lang, M., & Stelling, J. (2016). An orthogonal permease–inducer–repressor feedback loop shows bistability. ACS Synthetic Biology. American Chemical Society. https://doi.org/10.1021/acssynbio.6b00013","ista":"Gnügge R, Dharmarajan L, Lang M, Stelling J. 2016. An orthogonal permease–inducer–repressor feedback loop shows bistability. ACS Synthetic Biology. 5(10), 1098–1107.","ama":"Gnügge R, Dharmarajan L, Lang M, Stelling J. An orthogonal permease–inducer–repressor feedback loop shows bistability. ACS Synthetic Biology. 2016;5(10):1098-1107. doi:10.1021/acssynbio.6b00013","chicago":"Gnügge, Robert, Lekshmi Dharmarajan, Moritz Lang, and Jörg Stelling. “An Orthogonal Permease–Inducer–Repressor Feedback Loop Shows Bistability.” ACS Synthetic Biology. American Chemical Society, 2016. https://doi.org/10.1021/acssynbio.6b00013.","short":"R. Gnügge, L. Dharmarajan, M. Lang, J. Stelling, ACS Synthetic Biology 5 (2016) 1098–1107.","mla":"Gnügge, Robert, et al. “An Orthogonal Permease–Inducer–Repressor Feedback Loop Shows Bistability.” ACS Synthetic Biology, vol. 5, no. 10, American Chemical Society, 2016, pp. 1098–107, doi:10.1021/acssynbio.6b00013."},"publication":"ACS Synthetic Biology","page":"1098 - 1107","quality_controlled":"1","date_published":"2016-05-05T00:00:00Z","doi":"10.1021/acssynbio.6b00013","language":[{"iso":"eng"}],"day":"05","month":"05"},{"_id":"1170","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","intvolume":" 38","ddc":["003","518","570","621"],"status":"public","title":"Modular parameter identification of biomolecular networks","pubrep_id":"811","file":[{"access_level":"local","file_name":"IST-2017-811-v1+1_modular_parameter_identification.pdf","file_size":871964,"content_type":"application/pdf","creator":"system","relation":"main_file","file_id":"5095","checksum":"781bc3ffd30b2dd65b7727c5a285fc78","date_created":"2018-12-12T10:14:41Z","date_updated":"2020-07-14T12:44:37Z"}],"oa_version":"Submitted Version","type":"journal_article","issue":"6","abstract":[{"text":"The increasing complexity of dynamic models in systems and synthetic biology poses computational challenges especially for the identification of model parameters. While modularization of the corresponding optimization problems could help reduce the “curse of dimensionality,” abundant feedback and crosstalk mechanisms prohibit a simple decomposition of most biomolecular networks into subnetworks, or modules. Drawing on ideas from network modularization and multiple-shooting optimization, we present here a modular parameter identification approach that explicitly allows for such interdependencies. Interfaces between our modules are given by the experimentally measured molecular species. This definition allows deriving good (initial) estimates for the inter-module communication directly from the experimental data. Given these estimates, the states and parameter sensitivities of different modules can be integrated independently. To achieve consistency between modules, we iteratively adjust the estimates for inter-module communication while optimizing the parameters. After convergence to an optimal parameter set---but not during earlier iterations---the intermodule communication as well as the individual modules\\' state dynamics agree with the dynamics of the nonmodularized network. Our modular parameter identification approach allows for easy parallelization; it can reduce the computational complexity for larger networks and decrease the probability to converge to suboptimal local minima. We demonstrate the algorithm\\'s performance in parameter estimation for two biomolecular networks, a synthetic genetic oscillator and a mammalian signaling pathway.","lang":"eng"}],"citation":{"mla":"Lang, Moritz, and Jörg Stelling. “Modular Parameter Identification of Biomolecular Networks.” SIAM Journal on Scientific Computing, vol. 38, no. 6, Society for Industrial and Applied Mathematics , 2016, pp. B988–1008, doi:10.1137/15M103306X.","short":"M. Lang, J. Stelling, SIAM Journal on Scientific Computing 38 (2016) B988–B1008.","chicago":"Lang, Moritz, and Jörg Stelling. “Modular Parameter Identification of Biomolecular Networks.” SIAM Journal on Scientific Computing. Society for Industrial and Applied Mathematics , 2016. https://doi.org/10.1137/15M103306X.","ama":"Lang M, Stelling J. Modular parameter identification of biomolecular networks. SIAM Journal on Scientific Computing. 2016;38(6):B988-B1008. doi:10.1137/15M103306X","ista":"Lang M, Stelling J. 2016. Modular parameter identification of biomolecular networks. SIAM Journal on Scientific Computing. 38(6), B988–B1008.","apa":"Lang, M., & Stelling, J. (2016). Modular parameter identification of biomolecular networks. SIAM Journal on Scientific Computing. Society for Industrial and Applied Mathematics . https://doi.org/10.1137/15M103306X","ieee":"M. Lang and J. Stelling, “Modular parameter identification of biomolecular networks,” SIAM Journal on Scientific Computing, vol. 38, no. 6. Society for Industrial and Applied Mathematics , pp. B988–B1008, 2016."},"publication":"SIAM Journal on Scientific Computing","page":"B988 - B1008","date_published":"2016-11-15T00:00:00Z","scopus_import":1,"has_accepted_license":"1","day":"15","year":"2016","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publisher":"Society for Industrial and Applied Mathematics ","publication_status":"published","author":[{"full_name":"Lang, Moritz","last_name":"Lang","first_name":"Moritz","id":"29E0800A-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Jörg","last_name":"Stelling","full_name":"Stelling, Jörg"}],"volume":38,"date_updated":"2021-01-12T06:48:49Z","date_created":"2018-12-11T11:50:31Z","publist_id":"6186","file_date_updated":"2020-07-14T12:44:37Z","quality_controlled":"1","doi":"10.1137/15M103306X","language":[{"iso":"eng"}],"month":"11"},{"language":[{"iso":"eng"}],"conference":{"start_date":"2016-06-13","location":"Washington, D.C., USA","end_date":"2016-06-17","name":"AIAA: Aviation Technology, Integration, and Operations Conference"},"date_published":"2016-06-01T00:00:00Z","doi":"10.2514/6.2016-3764","quality_controlled":"1","page":"1 - 19","citation":{"chicago":"Mikić, Gregor, Alex Stoll, Joe Bevirt, Rok Grah, and Mark Moore. “Fuselage Boundary Layer Ingestion Propulsion Applied to a Thin Haul Commuter Aircraft for Optimal Efficiency,” 1–19. AIAA, 2016. https://doi.org/10.2514/6.2016-3764.","mla":"Mikić, Gregor, et al. Fuselage Boundary Layer Ingestion Propulsion Applied to a Thin Haul Commuter Aircraft for Optimal Efficiency. AIAA, 2016, pp. 1–19, doi:10.2514/6.2016-3764.","short":"G. Mikić, A. Stoll, J. Bevirt, R. Grah, M. Moore, in:, AIAA, 2016, pp. 1–19.","ista":"Mikić G, Stoll A, Bevirt J, Grah R, Moore M. 2016. Fuselage boundary layer ingestion propulsion applied to a thin haul commuter aircraft for optimal efficiency. AIAA: Aviation Technology, Integration, and Operations Conference, 1–19.","apa":"Mikić, G., Stoll, A., Bevirt, J., Grah, R., & Moore, M. (2016). Fuselage boundary layer ingestion propulsion applied to a thin haul commuter aircraft for optimal efficiency (pp. 1–19). Presented at the AIAA: Aviation Technology, Integration, and Operations Conference, Washington, D.C., USA: AIAA. https://doi.org/10.2514/6.2016-3764","ieee":"G. Mikić, A. Stoll, J. Bevirt, R. Grah, and M. Moore, “Fuselage boundary layer ingestion propulsion applied to a thin haul commuter aircraft for optimal efficiency,” presented at the AIAA: Aviation Technology, Integration, and Operations Conference, Washington, D.C., USA, 2016, pp. 1–19.","ama":"Mikić G, Stoll A, Bevirt J, Grah R, Moore M. Fuselage boundary layer ingestion propulsion applied to a thin haul commuter aircraft for optimal efficiency. In: AIAA; 2016:1-19. doi:10.2514/6.2016-3764"},"main_file_link":[{"url":"https://ntrs.nasa.gov/search.jsp?R=20160010167&hterms=Fuselage+boundary+layer+ingestion+propulsion+applied+thin+haul+commuter+aircraft+optimal+efficiency&qs=N%3D0%26Ntk%3DAll%26Ntt%3DFuselage%2520boundary%2520layer%2520ingestion%2520propulsion%2520applied%2520to%2520a%2520thin%2520haul%2520commuter%2520aircraft%2520for%2520optimal%2520efficiency%26Ntx%3Dmode%2520matchallpartial%26Nm%3D123%7CCollection%7CNASA%2520STI%7C%7C17%7CCollection%7CNACA","open_access":"1"}],"oa":1,"month":"06","day":"01","scopus_import":1,"date_created":"2018-12-11T11:50:47Z","date_updated":"2023-02-21T10:17:50Z","oa_version":"Preprint","author":[{"full_name":"Mikić, Gregor","first_name":"Gregor","last_name":"Mikić"},{"full_name":"Stoll, Alex","last_name":"Stoll","first_name":"Alex"},{"full_name":"Bevirt, Joe","first_name":"Joe","last_name":"Bevirt"},{"full_name":"Grah, Rok","first_name":"Rok","last_name":"Grah","id":"483E70DE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2539-3560"},{"first_name":"Mark","last_name":"Moore","full_name":"Moore, Mark"}],"status":"public","title":"Fuselage boundary layer ingestion propulsion applied to a thin haul commuter aircraft for optimal efficiency","publication_status":"published","publisher":"AIAA","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"year":"2016","_id":"1220","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","abstract":[{"lang":"eng","text":"Theoretical and numerical aspects of aerodynamic efficiency of propulsion systems coupled to the boundary layer of a fuselage are studied. We discuss the effects of local flow fields, which are affected both by conservative flow acceleration as well as total pressure losses, on the efficiency of boundary layer immersed propulsion devices. We introduce the concept of a boundary layer retardation turbine that helps reduce skin friction over the fuselage. We numerically investigate efficiency gains offered by boundary layer and wake interacting devices. We discuss the results in terms of a total energy consumption framework and show that efficiency gains of any device depend on all the other elements of the propulsion system."}],"publist_id":"6114","type":"conference"},{"author":[{"full_name":"Stone, Laura","first_name":"Laura","last_name":"Stone"},{"last_name":"Baym","first_name":"Michael","full_name":"Baym, Michael"},{"last_name":"Lieberman","first_name":"Tami","full_name":"Lieberman, Tami"},{"full_name":"Chait, Remy P","id":"3464AE84-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0876-3187","first_name":"Remy P","last_name":"Chait"},{"last_name":"Clardy","first_name":"Jon","full_name":"Clardy, Jon"},{"first_name":"Roy","last_name":"Kishony","full_name":"Kishony, Roy"}],"volume":12,"date_updated":"2021-01-12T06:49:39Z","date_created":"2018-12-11T11:51:10Z","acknowledgement":"This work was supported in part by National Institute of Allergy and Infectious Diseases grant U54 AI057159, US National Institutes of Health grants R01 GM081617 (to R.K.) and GM086258 (to J.C.), European Research Council FP7 ERC grant 281891 (to R.K.) and a National Science Foundation Graduate Fellowship (to L.K.S.).\r\n","year":"2016","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publisher":"Nature Publishing Group","publication_status":"published","publist_id":"6026","doi":"10.1038/nchembio.2176","language":[{"iso":"eng"}],"oa":1,"main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5069154/"}],"quality_controlled":"1","month":"11","oa_version":"Preprint","_id":"1290","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","intvolume":" 12","title":"Compounds that select against the tetracycline-resistance efflux pump","status":"public","issue":"11","abstract":[{"text":"We developed a competition-based screening strategy to identify compounds that invert the selective advantage of antibiotic resistance. Using our assay, we screened over 19,000 compounds for the ability to select against the TetA tetracycline-resistance efflux pump in Escherichia coli and identified two hits, β-thujaplicin and disulfiram. Treating a tetracycline-resistant population with β-thujaplicin selects for loss of the resistance gene, enabling an effective second-phase treatment with doxycycline.","lang":"eng"}],"type":"journal_article","date_published":"2016-11-01T00:00:00Z","citation":{"chicago":"Stone, Laura, Michael Baym, Tami Lieberman, Remy P Chait, Jon Clardy, and Roy Kishony. “Compounds That Select against the Tetracycline-Resistance Efflux Pump.” Nature Chemical Biology. Nature Publishing Group, 2016. https://doi.org/10.1038/nchembio.2176.","mla":"Stone, Laura, et al. “Compounds That Select against the Tetracycline-Resistance Efflux Pump.” Nature Chemical Biology, vol. 12, no. 11, Nature Publishing Group, 2016, pp. 902–04, doi:10.1038/nchembio.2176.","short":"L. Stone, M. Baym, T. Lieberman, R.P. Chait, J. Clardy, R. Kishony, Nature Chemical Biology 12 (2016) 902–904.","ista":"Stone L, Baym M, Lieberman T, Chait RP, Clardy J, Kishony R. 2016. Compounds that select against the tetracycline-resistance efflux pump. Nature Chemical Biology. 12(11), 902–904.","ieee":"L. Stone, M. Baym, T. Lieberman, R. P. Chait, J. Clardy, and R. Kishony, “Compounds that select against the tetracycline-resistance efflux pump,” Nature Chemical Biology, vol. 12, no. 11. Nature Publishing Group, pp. 902–904, 2016.","apa":"Stone, L., Baym, M., Lieberman, T., Chait, R. P., Clardy, J., & Kishony, R. (2016). Compounds that select against the tetracycline-resistance efflux pump. Nature Chemical Biology. Nature Publishing Group. https://doi.org/10.1038/nchembio.2176","ama":"Stone L, Baym M, Lieberman T, Chait RP, Clardy J, Kishony R. Compounds that select against the tetracycline-resistance efflux pump. Nature Chemical Biology. 2016;12(11):902-904. doi:10.1038/nchembio.2176"},"publication":"Nature Chemical Biology","page":"902 - 904","day":"01","scopus_import":1},{"citation":{"mla":"Lang, Moritz, and Eduardo Sontag. Scale-Invariant Systems Realize Nonlinear Differential Operators. Vol. 2016–July, 7526722, IEEE, 2016, doi:10.1109/ACC.2016.7526722.","short":"M. Lang, E. Sontag, in:, IEEE, 2016.","chicago":"Lang, Moritz, and Eduardo Sontag. “Scale-Invariant Systems Realize Nonlinear Differential Operators,” Vol. 2016–July. IEEE, 2016. https://doi.org/10.1109/ACC.2016.7526722.","ama":"Lang M, Sontag E. Scale-invariant systems realize nonlinear differential operators. In: Vol 2016-July. IEEE; 2016. doi:10.1109/ACC.2016.7526722","ista":"Lang M, Sontag E. 2016. Scale-invariant systems realize nonlinear differential operators. ACC: American Control Conference vol. 2016–July, 7526722.","apa":"Lang, M., & Sontag, E. (2016). Scale-invariant systems realize nonlinear differential operators (Vol. 2016–July). Presented at the ACC: American Control Conference, Boston, MA, USA: IEEE. https://doi.org/10.1109/ACC.2016.7526722","ieee":"M. Lang and E. Sontag, “Scale-invariant systems realize nonlinear differential operators,” presented at the ACC: American Control Conference, Boston, MA, USA, 2016, vol. 2016–July."},"date_published":"2016-07-28T00:00:00Z","scopus_import":1,"has_accepted_license":"1","day":"28","ddc":["003","621"],"status":"public","title":"Scale-invariant systems realize nonlinear differential operators","_id":"1320","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","oa_version":"Preprint","file":[{"content_type":"application/pdf","file_size":539166,"creator":"system","file_name":"IST-2017-810-v1+1_root.pdf","access_level":"local","date_created":"2018-12-12T10:16:17Z","date_updated":"2020-07-14T12:44:43Z","checksum":"7219432b43defc62a0d45f48d4ce6a19","relation":"main_file","file_id":"5203"}],"pubrep_id":"810","type":"conference","abstract":[{"text":"In recent years, several biomolecular systems have been shown to be scale-invariant (SI), i.e. to show the same output dynamics when exposed to geometrically scaled input signals (u → pu, p > 0) after pre-adaptation to accordingly scaled constant inputs. In this article, we show that SI systems-as well as systems invariant with respect to other input transformations-can realize nonlinear differential operators: when excited by inputs obeying functional forms characteristic for a given class of invariant systems, the systems' outputs converge to constant values directly quantifying the speed of the input.","lang":"eng"}],"project":[{"name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425"}],"quality_controlled":"1","language":[{"iso":"eng"}],"doi":"10.1109/ACC.2016.7526722","conference":{"end_date":"2016-07-08","start_date":"2016-07-06","location":"Boston, MA, USA","name":"ACC: American Control Conference"},"month":"07","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publisher":"IEEE","publication_status":"published","acknowledgement":"The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement n° [291734]. Work supported in part by grants AFOSR FA9550-14-1-0060 and NIH 1R01GM100473.","year":"2016","volume":"2016-July","date_updated":"2021-01-12T06:49:51Z","date_created":"2018-12-11T11:51:21Z","author":[{"last_name":"Lang","first_name":"Moritz","id":"29E0800A-F248-11E8-B48F-1D18A9856A87","full_name":"Lang, Moritz"},{"full_name":"Sontag, Eduardo","last_name":"Sontag","first_name":"Eduardo"}],"article_number":"7526722","publist_id":"5950","ec_funded":1,"file_date_updated":"2020-07-14T12:44:43Z"},{"abstract":[{"text":"Antibiotic-sensitive and -resistant bacteria coexist in natural environments with low, if detectable, antibiotic concentrations. Except possibly around localized antibiotic sources, where resistance can provide a strong advantage, bacterial fitness is dominated by stresses unaffected by resistance to the antibiotic. How do such mixed and heterogeneous conditions influence the selective advantage or disadvantage of antibiotic resistance? Here we find that sub-inhibitory levels of tetracyclines potentiate selection for or against tetracycline resistance around localized sources of almost any toxin or stress. Furthermore, certain stresses generate alternating rings of selection for and against resistance around a localized source of the antibiotic. In these conditions, localized antibiotic sources, even at high strengths, can actually produce a net selection against resistance to the antibiotic. Our results show that interactions between the effects of an antibiotic and other stresses in inhomogeneous environments can generate pervasive, complex patterns of selection both for and against antibiotic resistance.","lang":"eng"}],"type":"journal_article","pubrep_id":"662","file":[{"checksum":"ef147bcbb8bd37e9079cf3ce06f5815d","date_updated":"2020-07-14T12:44:44Z","date_created":"2018-12-12T10:13:52Z","file_id":"5039","relation":"main_file","creator":"system","file_size":1844107,"content_type":"application/pdf","access_level":"open_access","file_name":"IST-2016-662-v1+1_ncomms10333.pdf"}],"oa_version":"Published Version","_id":"1332","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","title":"Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments","status":"public","ddc":["570","579"],"intvolume":" 7","day":"20","has_accepted_license":"1","scopus_import":1,"date_published":"2016-01-20T00:00:00Z","publication":"Nature Communications","citation":{"chicago":"Chait, Remy P, Adam Palmer, Idan Yelin, and Roy Kishony. “Pervasive Selection for and against Antibiotic Resistance in Inhomogeneous Multistress Environments.” Nature Communications. Nature Publishing Group, 2016. https://doi.org/10.1038/ncomms10333.","short":"R.P. Chait, A. Palmer, I. Yelin, R. Kishony, Nature Communications 7 (2016).","mla":"Chait, Remy P., et al. “Pervasive Selection for and against Antibiotic Resistance in Inhomogeneous Multistress Environments.” Nature Communications, vol. 7, 10333, Nature Publishing Group, 2016, doi:10.1038/ncomms10333.","apa":"Chait, R. P., Palmer, A., Yelin, I., & Kishony, R. (2016). Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments. Nature Communications. Nature Publishing Group. https://doi.org/10.1038/ncomms10333","ieee":"R. P. Chait, A. Palmer, I. Yelin, and R. Kishony, “Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments,” Nature Communications, vol. 7. Nature Publishing Group, 2016.","ista":"Chait RP, Palmer A, Yelin I, Kishony R. 2016. Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments. Nature Communications. 7, 10333.","ama":"Chait RP, Palmer A, Yelin I, Kishony R. Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments. Nature Communications. 2016;7. doi:10.1038/ncomms10333"},"file_date_updated":"2020-07-14T12:44:44Z","publist_id":"5936","article_number":"10333","author":[{"first_name":"Remy P","last_name":"Chait","id":"3464AE84-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0876-3187","full_name":"Chait, Remy P"},{"full_name":"Palmer, Adam","first_name":"Adam","last_name":"Palmer"},{"full_name":"Yelin, Idan","last_name":"Yelin","first_name":"Idan"},{"first_name":"Roy","last_name":"Kishony","full_name":"Kishony, Roy"}],"date_updated":"2021-01-12T06:49:57Z","date_created":"2018-12-11T11:51:25Z","volume":7,"year":"2016","acknowledgement":"This work was partially supported by US National Institutes of Health grant R01-GM081617, Israeli Centers of Research Excellence I-CORE Program ISF Grant No. 152/11, and the European Research Council FP7 ERC Grant 281891.","publication_status":"published","publisher":"Nature Publishing Group","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"month":"01","doi":"10.1038/ncomms10333","language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"quality_controlled":"1"},{"date_created":"2018-12-11T11:51:29Z","date_updated":"2021-01-12T06:50:01Z","oa_version":"Preprint","volume":353,"author":[{"last_name":"Baym","first_name":"Michael","full_name":"Baym, Michael"},{"last_name":"Lieberman","first_name":"Tami","full_name":"Lieberman, Tami"},{"last_name":"Kelsic","first_name":"Eric","full_name":"Kelsic, Eric"},{"full_name":"Chait, Remy P","last_name":"Chait","first_name":"Remy P","orcid":"0000-0003-0876-3187","id":"3464AE84-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Rotem","last_name":"Gross","full_name":"Gross, Rotem"},{"full_name":"Yelin, Idan","first_name":"Idan","last_name":"Yelin"},{"last_name":"Kishony","first_name":"Roy","full_name":"Kishony, Roy"}],"title":"Spatiotemporal microbial evolution on antibiotic landscapes","publication_status":"published","status":"public","publisher":"American Association for the Advancement of Science","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"intvolume":" 353","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","_id":"1342","year":"2016","abstract":[{"lang":"eng","text":"A key aspect of bacterial survival is the ability to evolve while migrating across spatially varying environmental challenges. Laboratory experiments, however, often study evolution in well-mixed systems. Here, we introduce an experimental device, the microbial evolution and growth arena (MEGA)-plate, in which bacteria spread and evolved on a large antibiotic landscape (120 × 60 centimeters) that allowed visual observation of mutation and selection in a migrating bacterial front.While resistance increased consistently, multiple coexisting lineages diversified both phenotypically and genotypically. Analyzing mutants at and behind the propagating front,we found that evolution is not always led by the most resistant mutants; highly resistant mutants may be trapped behindmore sensitive lineages.TheMEGA-plate provides a versatile platformfor studying microbial adaption and directly visualizing evolutionary dynamics."}],"issue":"6304","publist_id":"5911","type":"journal_article","language":[{"iso":"eng"}],"date_published":"2016-09-09T00:00:00Z","doi":"10.1126/science.aag0822","quality_controlled":"1","page":"1147 - 1151","publication":"Science","main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5534434/"}],"oa":1,"citation":{"ista":"Baym M, Lieberman T, Kelsic E, Chait RP, Gross R, Yelin I, Kishony R. 2016. Spatiotemporal microbial evolution on antibiotic landscapes. Science. 353(6304), 1147–1151.","ieee":"M. Baym et al., “Spatiotemporal microbial evolution on antibiotic landscapes,” Science, vol. 353, no. 6304. American Association for the Advancement of Science, pp. 1147–1151, 2016.","apa":"Baym, M., Lieberman, T., Kelsic, E., Chait, R. P., Gross, R., Yelin, I., & Kishony, R. (2016). Spatiotemporal microbial evolution on antibiotic landscapes. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.aag0822","ama":"Baym M, Lieberman T, Kelsic E, et al. Spatiotemporal microbial evolution on antibiotic landscapes. Science. 2016;353(6304):1147-1151. doi:10.1126/science.aag0822","chicago":"Baym, Michael, Tami Lieberman, Eric Kelsic, Remy P Chait, Rotem Gross, Idan Yelin, and Roy Kishony. “Spatiotemporal Microbial Evolution on Antibiotic Landscapes.” Science. American Association for the Advancement of Science, 2016. https://doi.org/10.1126/science.aag0822.","mla":"Baym, Michael, et al. “Spatiotemporal Microbial Evolution on Antibiotic Landscapes.” Science, vol. 353, no. 6304, American Association for the Advancement of Science, 2016, pp. 1147–51, doi:10.1126/science.aag0822.","short":"M. Baym, T. Lieberman, E. Kelsic, R.P. Chait, R. Gross, I. Yelin, R. Kishony, Science 353 (2016) 1147–1151."},"month":"09","day":"09","scopus_import":1},{"day":"20","has_accepted_license":"1","scopus_import":1,"date_published":"2016-07-20T00:00:00Z","page":"1163 - 1170","publication":"Proceedings of the Genetic and Evolutionary Computation Conference 2016 ","citation":{"chicago":"Oliveto, Pietro, Tiago Paixao, Jorge Heredia, Dirk Sudholt, and Barbora Trubenova. “When Non-Elitism Outperforms Elitism for Crossing Fitness Valleys.” In Proceedings of the Genetic and Evolutionary Computation Conference 2016 , 1163–70. ACM, 2016. https://doi.org/10.1145/2908812.2908909.","mla":"Oliveto, Pietro, et al. “When Non-Elitism Outperforms Elitism for Crossing Fitness Valleys.” Proceedings of the Genetic and Evolutionary Computation Conference 2016 , ACM, 2016, pp. 1163–70, doi:10.1145/2908812.2908909.","short":"P. Oliveto, T. Paixao, J. Heredia, D. Sudholt, B. Trubenova, in:, Proceedings of the Genetic and Evolutionary Computation Conference 2016 , ACM, 2016, pp. 1163–1170.","ista":"Oliveto P, Paixao T, Heredia J, Sudholt D, Trubenova B. 2016. When non-elitism outperforms elitism for crossing fitness valleys. Proceedings of the Genetic and Evolutionary Computation Conference 2016 . GECCO: Genetic and evolutionary computation conference, 1163–1170.","apa":"Oliveto, P., Paixao, T., Heredia, J., Sudholt, D., & Trubenova, B. (2016). When non-elitism outperforms elitism for crossing fitness valleys. In Proceedings of the Genetic and Evolutionary Computation Conference 2016 (pp. 1163–1170). Denver, CO, USA: ACM. https://doi.org/10.1145/2908812.2908909","ieee":"P. Oliveto, T. Paixao, J. Heredia, D. Sudholt, and B. Trubenova, “When non-elitism outperforms elitism for crossing fitness valleys,” in Proceedings of the Genetic and Evolutionary Computation Conference 2016 , Denver, CO, USA, 2016, pp. 1163–1170.","ama":"Oliveto P, Paixao T, Heredia J, Sudholt D, Trubenova B. When non-elitism outperforms elitism for crossing fitness valleys. In: Proceedings of the Genetic and Evolutionary Computation Conference 2016 . ACM; 2016:1163-1170. doi:10.1145/2908812.2908909"},"abstract":[{"lang":"eng","text":"Crossing fitness valleys is one of the major obstacles to function optimization. In this paper we investigate how the structure of the fitness valley, namely its depth d and length ℓ, influence the runtime of different strategies for crossing these valleys. We present a runtime comparison between the (1+1) EA and two non-elitist nature-inspired algorithms, Strong Selection Weak Mutation (SSWM) and the Metropolis algorithm. While the (1+1) EA has to jump across the valley to a point of higher fitness because it does not accept decreasing moves, the non-elitist algorithms may cross the valley by accepting worsening moves. We show that while the runtime of the (1+1) EA algorithm depends critically on the length of the valley, the runtimes of the non-elitist algorithms depend crucially only on the depth of the valley. In particular, the expected runtime of both SSWM and Metropolis is polynomial in ℓ and exponential in d while the (1+1) EA is efficient only for valleys of small length. Moreover, we show that both SSWM and Metropolis can also efficiently optimize a rugged function consisting of consecutive valleys."}],"type":"conference","oa_version":"Published Version","file":[{"date_created":"2018-12-12T10:16:27Z","date_updated":"2020-07-14T12:44:45Z","checksum":"a1896e39e4113f2711e46b435d5f3e69","relation":"main_file","file_id":"5214","content_type":"application/pdf","file_size":979026,"creator":"system","file_name":"IST-2016-650-v1+1_p1163-oliveto.pdf","access_level":"open_access"}],"pubrep_id":"650","status":"public","ddc":["576"],"title":"When non-elitism outperforms elitism for crossing fitness valleys","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","_id":"1349","month":"07","language":[{"iso":"eng"}],"conference":{"start_date":"2016-07-20","location":"Denver, CO, USA","end_date":"2016-07-24","name":"GECCO: Genetic and evolutionary computation conference"},"doi":"10.1145/2908812.2908909","quality_controlled":"1","project":[{"name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","call_identifier":"FP7","grant_number":"618091","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425"}],"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"file_date_updated":"2020-07-14T12:44:45Z","ec_funded":1,"publist_id":"5900","date_created":"2018-12-11T11:51:31Z","date_updated":"2021-01-12T06:50:03Z","author":[{"first_name":"Pietro","last_name":"Oliveto","full_name":"Oliveto, Pietro"},{"last_name":"Paixao","first_name":"Tiago","orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","full_name":"Paixao, Tiago"},{"full_name":"Heredia, Jorge","last_name":"Heredia","first_name":"Jorge"},{"full_name":"Sudholt, Dirk","last_name":"Sudholt","first_name":"Dirk"},{"first_name":"Barbora","last_name":"Trubenova","id":"42302D54-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6873-2967","full_name":"Trubenova, Barbora"}],"publication_status":"published","department":[{"_id":"NiBa"},{"_id":"CaGu"}],"publisher":"ACM","year":"2016"},{"day":"19","article_processing_charge":"No","scopus_import":1,"date_published":"2016-04-19T00:00:00Z","publication":"PNAS","citation":{"chicago":"Paixao, Tiago, and Nicholas H Barton. “The Effect of Gene Interactions on the Long-Term Response to Selection.” PNAS. National Academy of Sciences, 2016. https://doi.org/10.1073/pnas.1518830113.","short":"T. Paixao, N.H. Barton, PNAS 113 (2016) 4422–4427.","mla":"Paixao, Tiago, and Nicholas H. Barton. “The Effect of Gene Interactions on the Long-Term Response to Selection.” PNAS, vol. 113, no. 16, National Academy of Sciences, 2016, pp. 4422–27, doi:10.1073/pnas.1518830113.","apa":"Paixao, T., & Barton, N. H. (2016). The effect of gene interactions on the long-term response to selection. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.1518830113","ieee":"T. Paixao and N. H. Barton, “The effect of gene interactions on the long-term response to selection,” PNAS, vol. 113, no. 16. National Academy of Sciences, pp. 4422–4427, 2016.","ista":"Paixao T, Barton NH. 2016. The effect of gene interactions on the long-term response to selection. PNAS. 113(16), 4422–4427.","ama":"Paixao T, Barton NH. The effect of gene interactions on the long-term response to selection. PNAS. 2016;113(16):4422-4427. doi:10.1073/pnas.1518830113"},"article_type":"original","page":"4422 - 4427","abstract":[{"lang":"eng","text":"The role of gene interactions in the evolutionary process has long\r\nbeen controversial. Although some argue that they are not of\r\nimportance, because most variation is additive, others claim that\r\ntheir effect in the long term can be substantial. Here, we focus on\r\nthe long-term effects of genetic interactions under directional\r\nselection assuming no mutation or dominance, and that epistasis is\r\nsymmetrical overall. We ask by how much the mean of a complex\r\ntrait can be increased by selection and analyze two extreme\r\nregimes, in which either drift or selection dominate the dynamics\r\nof allele frequencies. In both scenarios, epistatic interactions affect\r\nthe long-term response to selection by modulating the additive\r\ngenetic variance. When drift dominates, we extend Robertson\r\n’\r\ns\r\n[Robertson A (1960)\r\nProc R Soc Lond B Biol Sci\r\n153(951):234\r\n−\r\n249]\r\nargument to show that, for any form of epistasis, the total response\r\nof a haploid population is proportional to the initial total genotypic\r\nvariance. In contrast, the total response of a diploid population is\r\nincreased by epistasis, for a given initial genotypic variance. When\r\nselection dominates, we show that the total selection response can\r\nonly be increased by epistasis when s\r\nome initially deleterious alleles\r\nbecome favored as the genetic background changes. We find a sim-\r\nple approximation for this effect and show that, in this regime, it is\r\nthe structure of the genotype - phenotype map that matters and not\r\nthe variance components of the population."}],"issue":"16","type":"journal_article","oa_version":"Published Version","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"1359","status":"public","title":"The effect of gene interactions on the long-term response to selection","intvolume":" 113","month":"04","doi":"10.1073/pnas.1518830113","language":[{"iso":"eng"}],"external_id":{"pmid":["27044080"]},"oa":1,"main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4843425/","open_access":"1"}],"quality_controlled":"1","project":[{"name":"Limits to selection in biology and in evolutionary computation","call_identifier":"FP7","grant_number":"250152","_id":"25B07788-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FP7","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","grant_number":"618091"}],"publist_id":"5886","ec_funded":1,"author":[{"id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2361-3953","first_name":"Tiago","last_name":"Paixao","full_name":"Paixao, Tiago"},{"last_name":"Barton","first_name":"Nicholas H","orcid":"0000-0002-8548-5240","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","full_name":"Barton, Nicholas H"}],"date_updated":"2021-01-12T06:50:08Z","date_created":"2018-12-11T11:51:34Z","volume":113,"year":"2016","pmid":1,"publication_status":"published","publisher":"National Academy of Sciences","department":[{"_id":"NiBa"},{"_id":"CaGu"}]},{"oa_version":"Published Version","file":[{"file_name":"IST-2016-588-v1+1_Mol_Biol_Evol-2016-Lagator-761-9.pdf","access_level":"open_access","file_size":648115,"content_type":"application/pdf","creator":"system","relation":"main_file","file_id":"4751","date_created":"2018-12-12T10:09:27Z","date_updated":"2020-07-14T12:44:53Z","checksum":"1f456ce1d2aa2f67176a1709f9702ecf"}],"pubrep_id":"588","ddc":["570","576"],"title":"Epistatic interactions in the arabinose cis-regulatory element","status":"public","intvolume":" 33","_id":"1427","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","abstract":[{"lang":"eng","text":"Changes in gene expression are an important mode of evolution; however, the proximate mechanism of these changes is poorly understood. In particular, little is known about the effects of mutations within cis binding sites for transcription factors, or the nature of epistatic interactions between these mutations. Here, we tested the effects of single and double mutants in two cis binding sites involved in the transcriptional regulation of the Escherichia coli araBAD operon, a component of arabinose metabolism, using a synthetic system. This system decouples transcriptional control from any posttranslational effects on fitness, allowing a precise estimate of the effect of single and double mutations, and hence epistasis, on gene expression. We found that epistatic interactions between mutations in the araBAD cis-regulatory element are common, and that the predominant form of epistasis is negative. The magnitude of the interactions depended on whether the mutations are located in the same or in different operator sites. Importantly, these epistatic interactions were dependent on the presence of arabinose, a native inducer of the araBAD operon in vivo, with some interactions changing in sign (e.g., from negative to positive) in its presence. This study thus reveals that mutations in even relatively simple cis-regulatory elements interact in complex ways such that selection on the level of gene expression in one environment might perturb regulation in the other environment in an unpredictable and uncorrelated manner."}],"issue":"3","type":"journal_article","date_published":"2016-03-01T00:00:00Z","page":"761 - 769","publication":"Molecular Biology and Evolution","citation":{"ama":"Lagator M, Igler C, Moreno A, Guet CC, Bollback JP. Epistatic interactions in the arabinose cis-regulatory element. Molecular Biology and Evolution. 2016;33(3):761-769. doi:10.1093/molbev/msv269","ista":"Lagator M, Igler C, Moreno A, Guet CC, Bollback JP. 2016. Epistatic interactions in the arabinose cis-regulatory element. Molecular Biology and Evolution. 33(3), 761–769.","apa":"Lagator, M., Igler, C., Moreno, A., Guet, C. C., & Bollback, J. P. (2016). Epistatic interactions in the arabinose cis-regulatory element. Molecular Biology and Evolution. Oxford University Press. https://doi.org/10.1093/molbev/msv269","ieee":"M. Lagator, C. Igler, A. Moreno, C. C. Guet, and J. P. Bollback, “Epistatic interactions in the arabinose cis-regulatory element,” Molecular Biology and Evolution, vol. 33, no. 3. Oxford University Press, pp. 761–769, 2016.","mla":"Lagator, Mato, et al. “Epistatic Interactions in the Arabinose Cis-Regulatory Element.” Molecular Biology and Evolution, vol. 33, no. 3, Oxford University Press, 2016, pp. 761–69, doi:10.1093/molbev/msv269.","short":"M. Lagator, C. Igler, A. Moreno, C.C. Guet, J.P. Bollback, Molecular Biology and Evolution 33 (2016) 761–769.","chicago":"Lagator, Mato, Claudia Igler, Anaisa Moreno, Calin C Guet, and Jonathan P Bollback. “Epistatic Interactions in the Arabinose Cis-Regulatory Element.” Molecular Biology and Evolution. Oxford University Press, 2016. https://doi.org/10.1093/molbev/msv269."},"day":"01","has_accepted_license":"1","scopus_import":1,"date_created":"2018-12-11T11:51:57Z","date_updated":"2021-01-12T06:50:39Z","volume":33,"author":[{"last_name":"Lagator","first_name":"Mato","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","full_name":"Lagator, Mato"},{"full_name":"Igler, Claudia","first_name":"Claudia","last_name":"Igler","id":"46613666-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Moreno","first_name":"Anaisa","full_name":"Moreno, Anaisa"},{"full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet"},{"full_name":"Bollback, Jonathan P","last_name":"Bollback","first_name":"Jonathan P","orcid":"0000-0002-4624-4612","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87"}],"publication_status":"published","publisher":"Oxford University Press","department":[{"_id":"CaGu"},{"_id":"JoBo"}],"year":"2016","file_date_updated":"2020-07-14T12:44:53Z","ec_funded":1,"publist_id":"5772","language":[{"iso":"eng"}],"doi":"10.1093/molbev/msv269","quality_controlled":"1","project":[{"_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734","call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme"}],"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"month":"03"},{"language":[{"iso":"eng"}],"conference":{"name":"HSB: Hybrid Systems Biology","end_date":"2015-09-05","location":"Madrid, Spain","start_date":"2015-09-04"},"doi":"10.1007/978-3-319-26916-0_10","quality_controlled":"1","project":[{"call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme","grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425"}],"oa":1,"main_file_link":[{"open_access":"1","url":"http://arxiv.org/abs/1501.00440"}],"month":"01","date_updated":"2021-01-12T06:51:22Z","date_created":"2018-12-11T11:52:31Z","volume":9271,"author":[{"last_name":"Beica","first_name":"Andreea","full_name":"Beica, Andreea"},{"full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet"},{"full_name":"Petrov, Tatjana","id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9041-0905","first_name":"Tatjana","last_name":"Petrov"}],"publication_status":"published","publisher":"Springer","department":[{"_id":"CaGu"},{"_id":"ToHe"}],"acknowledgement":"This research was supported by the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. 291734, and the SNSF Early Postdoc.Mobility Fellowship, the grant number P2EZP2_148797.","year":"2016","ec_funded":1,"publist_id":"5649","date_published":"2016-01-10T00:00:00Z","page":"173 - 191","citation":{"ista":"Beica A, Guet CC, Petrov T. 2016. Efficient reduction of kappa models by static inspection of the rule-set. HSB: Hybrid Systems Biology, LNCS, vol. 9271, 173–191.","apa":"Beica, A., Guet, C. C., & Petrov, T. (2016). Efficient reduction of kappa models by static inspection of the rule-set (Vol. 9271, pp. 173–191). Presented at the HSB: Hybrid Systems Biology, Madrid, Spain: Springer. https://doi.org/10.1007/978-3-319-26916-0_10","ieee":"A. Beica, C. C. Guet, and T. Petrov, “Efficient reduction of kappa models by static inspection of the rule-set,” presented at the HSB: Hybrid Systems Biology, Madrid, Spain, 2016, vol. 9271, pp. 173–191.","ama":"Beica A, Guet CC, Petrov T. Efficient reduction of kappa models by static inspection of the rule-set. In: Vol 9271. Springer; 2016:173-191. doi:10.1007/978-3-319-26916-0_10","chicago":"Beica, Andreea, Calin C Guet, and Tatjana Petrov. “Efficient Reduction of Kappa Models by Static Inspection of the Rule-Set,” 9271:173–91. Springer, 2016. https://doi.org/10.1007/978-3-319-26916-0_10.","mla":"Beica, Andreea, et al. Efficient Reduction of Kappa Models by Static Inspection of the Rule-Set. Vol. 9271, Springer, 2016, pp. 173–91, doi:10.1007/978-3-319-26916-0_10.","short":"A. Beica, C.C. Guet, T. Petrov, in:, Springer, 2016, pp. 173–191."},"day":"10","scopus_import":1,"oa_version":"Preprint","title":"Efficient reduction of kappa models by static inspection of the rule-set","status":"public","intvolume":" 9271","_id":"1524","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","abstract":[{"text":"When designing genetic circuits, the typical primitives used in major existing modelling formalisms are gene interaction graphs, where edges between genes denote either an activation or inhibition relation. However, when designing experiments, it is important to be precise about the low-level mechanistic details as to how each such relation is implemented. The rule-based modelling language Kappa allows to unambiguously specify mechanistic details such as DNA binding sites, dimerisation of transcription factors, or co-operative interactions. Such a detailed description comes with complexity and computationally costly executions. We propose a general method for automatically transforming a rule-based program, by eliminating intermediate species and adjusting the rate constants accordingly. To the best of our knowledge, we show the first automated reduction of rule-based models based on equilibrium approximations.\r\nOur algorithm is an adaptation of an existing algorithm, which was designed for reducing reaction-based programs; our version of the algorithm scans the rule-based Kappa model in search for those interaction patterns known to be amenable to equilibrium approximations (e.g. Michaelis-Menten scheme). Additional checks are then performed in order to verify if the reduction is meaningful in the context of the full model. The reduced model is efficiently obtained by static inspection over the rule-set. The tool is tested on a detailed rule-based model of a λ-phage switch, which lists 92 rules and 13 agents. The reduced model has 11 rules and 5 agents, and provides a dramatic reduction in simulation time of several orders of magnitude.","lang":"eng"}],"alternative_title":["LNCS"],"type":"conference"},{"type":"journal_article","issue":"4","abstract":[{"text":"In bacteria, replicative aging manifests as a difference in growth or survival between the two cells emerging from division. One cell can be regarded as an aging mother with a decreased potential for future survival and division, the other as a rejuvenated daughter. Here, we aimed at investigating some of the processes involved in aging in the bacterium Escherichia coli, where the two types of cells can be distinguished by the age of their cell poles. We found that certain changes in the regulation of the carbohydrate metabolism can affect aging. A mutation in the carbon storage regulator gene, csrA, leads to a dramatically shorter replicative lifespan; csrA mutants stop dividing once their pole exceeds an age of about five divisions. These old-pole cells accumulate glycogen at their old cell poles; after their last division, they do not contain a chromosome, presumably because of spatial exclusion by the glycogen aggregates. The new-pole daughters produced by these aging mothers are born young; they only express the deleterious phenotype once their pole is old. These results demonstrate how manipulations of nutrient allocation can lead to the exclusion of the chromosome and limit replicative lifespan in E. coli, and illustrate how mutations can have phenotypic effects that are specific for cells with old poles. This raises the question how bacteria can avoid the accumulation of such mutations in their genomes over evolutionary times, and how they can achieve the long replicative lifespans that have recently been reported.","lang":"eng"}],"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","_id":"1250","intvolume":" 12","ddc":["576","579"],"title":"Genetic manipulation of glycogen allocation affects replicative lifespan in E coli","status":"public","pubrep_id":"705","oa_version":"Published Version","file":[{"file_id":"5067","relation":"main_file","date_updated":"2020-07-14T12:44:41Z","date_created":"2018-12-12T10:14:17Z","checksum":"53d22b2b39e5adc243d34f18b2615a85","file_name":"IST-2016-705-v1+1_journal.pgen.1005974.PDF","access_level":"open_access","creator":"system","file_size":6273249,"content_type":"application/pdf"}],"scopus_import":1,"has_accepted_license":"1","day":"19","citation":{"chicago":"Boehm, Alex, Markus Arnoldini, Tobias Bergmiller, Thomas Röösli, Colette Bigosch, and Martin Ackermann. “Genetic Manipulation of Glycogen Allocation Affects Replicative Lifespan in E Coli.” PLoS Genetics. Public Library of Science, 2016. https://doi.org/10.1371/journal.pgen.1005974.","mla":"Boehm, Alex, et al. “Genetic Manipulation of Glycogen Allocation Affects Replicative Lifespan in E Coli.” PLoS Genetics, vol. 12, no. 4, e1005974, Public Library of Science, 2016, doi:10.1371/journal.pgen.1005974.","short":"A. Boehm, M. Arnoldini, T. Bergmiller, T. Röösli, C. Bigosch, M. Ackermann, PLoS Genetics 12 (2016).","ista":"Boehm A, Arnoldini M, Bergmiller T, Röösli T, Bigosch C, Ackermann M. 2016. Genetic manipulation of glycogen allocation affects replicative lifespan in E coli. PLoS Genetics. 12(4), e1005974.","apa":"Boehm, A., Arnoldini, M., Bergmiller, T., Röösli, T., Bigosch, C., & Ackermann, M. (2016). Genetic manipulation of glycogen allocation affects replicative lifespan in E coli. PLoS Genetics. Public Library of Science. https://doi.org/10.1371/journal.pgen.1005974","ieee":"A. Boehm, M. Arnoldini, T. Bergmiller, T. Röösli, C. Bigosch, and M. Ackermann, “Genetic manipulation of glycogen allocation affects replicative lifespan in E coli,” PLoS Genetics, vol. 12, no. 4. Public Library of Science, 2016.","ama":"Boehm A, Arnoldini M, Bergmiller T, Röösli T, Bigosch C, Ackermann M. Genetic manipulation of glycogen allocation affects replicative lifespan in E coli. PLoS Genetics. 2016;12(4). doi:10.1371/journal.pgen.1005974"},"publication":"PLoS Genetics","date_published":"2016-04-19T00:00:00Z","article_number":"e1005974","publist_id":"6077","file_date_updated":"2020-07-14T12:44:41Z","year":"2016","acknowledgement":"This manuscript is dedicated to the memory of Alex Böhm, who was a great friend and a passionate biologist. Alex passed away after the initial submission of this manuscript. We thank Vesna Olivera and Ursula Sauder from the Zentrum für Mikroskopie Uni Basel for excellent service, and Olin Silander, Nikki Freed, and Nela Nikolic for helpful discussions. This work was supported by the Swiss National Science Foundation grants to M. Ackermann and Urs Jenal (supporting AB).","publisher":"Public Library of Science","department":[{"_id":"CaGu"}],"publication_status":"published","related_material":{"record":[{"status":"public","relation":"research_data","id":"9873"}]},"author":[{"first_name":"Alex","last_name":"Boehm","full_name":"Boehm, Alex"},{"first_name":"Markus","last_name":"Arnoldini","full_name":"Arnoldini, Markus"},{"full_name":"Bergmiller, Tobias","orcid":"0000-0001-5396-4346","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","last_name":"Bergmiller","first_name":"Tobias"},{"last_name":"Röösli","first_name":"Thomas","full_name":"Röösli, Thomas"},{"full_name":"Bigosch, Colette","first_name":"Colette","last_name":"Bigosch"},{"first_name":"Martin","last_name":"Ackermann","full_name":"Ackermann, Martin"}],"volume":12,"date_created":"2018-12-11T11:50:56Z","date_updated":"2023-02-23T14:11:39Z","month":"04","oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"quality_controlled":"1","doi":"10.1371/journal.pgen.1005974","language":[{"iso":"eng"}]},{"doi":"10.1371/journal.pgen.1005974.s015","citation":{"ama":"Boehm A, Arnoldini M, Bergmiller T, Röösli T, Bigosch C, Ackermann M. Quantification of the growth rate reduction as a consequence of age-specific mortality. 2016. doi:10.1371/journal.pgen.1005974.s015","ista":"Boehm A, Arnoldini M, Bergmiller T, Röösli T, Bigosch C, Ackermann M. 2016. Quantification of the growth rate reduction as a consequence of age-specific mortality, Public Library of Science, 10.1371/journal.pgen.1005974.s015.","ieee":"A. Boehm, M. Arnoldini, T. Bergmiller, T. Röösli, C. Bigosch, and M. Ackermann, “Quantification of the growth rate reduction as a consequence of age-specific mortality.” Public Library of Science, 2016.","apa":"Boehm, A., Arnoldini, M., Bergmiller, T., Röösli, T., Bigosch, C., & Ackermann, M. (2016). Quantification of the growth rate reduction as a consequence of age-specific mortality. Public Library of Science. https://doi.org/10.1371/journal.pgen.1005974.s015","mla":"Boehm, Alex, et al. Quantification of the Growth Rate Reduction as a Consequence of Age-Specific Mortality. Public Library of Science, 2016, doi:10.1371/journal.pgen.1005974.s015.","short":"A. Boehm, M. Arnoldini, T. Bergmiller, T. Röösli, C. Bigosch, M. Ackermann, (2016).","chicago":"Boehm, Alex, Markus Arnoldini, Tobias Bergmiller, Thomas Röösli, Colette Bigosch, and Martin Ackermann. “Quantification of the Growth Rate Reduction as a Consequence of Age-Specific Mortality.” Public Library of Science, 2016. https://doi.org/10.1371/journal.pgen.1005974.s015."},"month":"04","day":"19","article_processing_charge":"No","date_updated":"2023-02-21T16:50:13Z","date_created":"2021-08-10T09:42:34Z","oa_version":"Published Version","author":[{"full_name":"Boehm, Alex","first_name":"Alex","last_name":"Boehm"},{"full_name":"Arnoldini, Markus","first_name":"Markus","last_name":"Arnoldini"},{"full_name":"Bergmiller, Tobias","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5396-4346","first_name":"Tobias","last_name":"Bergmiller"},{"first_name":"Thomas","last_name":"Röösli","full_name":"Röösli, Thomas"},{"first_name":"Colette","last_name":"Bigosch","full_name":"Bigosch, Colette"},{"full_name":"Ackermann, Martin","first_name":"Martin","last_name":"Ackermann"}],"related_material":{"record":[{"relation":"used_in_publication","status":"public","id":"1250"}]},"title":"Quantification of the growth rate reduction as a consequence of age-specific mortality","status":"public","department":[{"_id":"CaGu"}],"publisher":"Public Library of Science","_id":"9873","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","year":"2016","type":"research_data_reference"},{"volume":33,"date_updated":"2023-09-05T13:46:05Z","date_created":"2018-12-18T13:18:10Z","related_material":{"record":[{"id":"9719","relation":"research_data","status":"public"}]},"author":[{"first_name":"Sébastien","last_name":"Wielgoss","full_name":"Wielgoss, Sébastien"},{"orcid":"0000-0001-5396-4346","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","last_name":"Bergmiller","first_name":"Tobias","full_name":"Bergmiller, Tobias"},{"first_name":"Anna M.","last_name":"Bischofberger","full_name":"Bischofberger, Anna M."},{"full_name":"Hall, Alex R.","last_name":"Hall","first_name":"Alex R."}],"publisher":"Oxford University Press","department":[{"_id":"CaGu"}],"publication_status":"published","pmid":1,"year":"2016","acknowledgement":"The authors thank three anonymous reviewers and the editor for helpful comments on the manuscript, as well as Dominique Schneider for feedback on an earlier draft, Jenna Gallie for lytic λ and Julien Capelle for T5 and T6. This work was supported by the Swiss National Science Foundation (PZ00P3_148255 to A.H.) and an EU Marie Curie PEOPLE Postdoctoral Fellowship for Career Development (FP7-PEOPLE-2012-IEF-331824 to S.W.).","file_date_updated":"2020-07-14T12:47:10Z","language":[{"iso":"eng"}],"doi":"10.1093/molbev/msv270","quality_controlled":"1","tmp":{"name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","image":"/images/cc_by_nc.png","short":"CC BY-NC (4.0)"},"external_id":{"pmid":["26609077"]},"oa":1,"publication_identifier":{"eissn":["1537-1719"],"issn":["0737-4038"]},"month":"03","file":[{"content_type":"application/pdf","file_size":634037,"creator":"dernst","access_level":"open_access","file_name":"2016_MolBiolEvol_Wielgoss.pdf","checksum":"47d9010690b6c5c17f2ac830cc63ac5c","date_created":"2018-12-18T13:21:45Z","date_updated":"2020-07-14T12:47:10Z","relation":"main_file","file_id":"5750"}],"oa_version":"Published Version","pubrep_id":"587","intvolume":" 33","title":"Adaptation to parasites and costs of parasite resistance in mutator and nonmutator bacteria","ddc":["576"],"status":"public","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"5749","issue":"3","abstract":[{"lang":"eng","text":"Parasitism creates selection for resistance mechanisms in host populations and is hypothesized to promote increased host evolvability. However, the influence of these traits on host evolution when parasites are no longer present is unclear. We used experimental evolution and whole-genome sequencing of Escherichia coli to determine the effects of past and present exposure to parasitic viruses (phages) on the spread of mutator alleles, resistance, and bacterial competitive fitness. We found that mutator alleles spread rapidly during adaptation to any of four different phage species, and this pattern was even more pronounced with multiple phages present simultaneously. However, hypermutability did not detectably accelerate adaptation in the absence of phages and recovery of fitness costs associated with resistance. Several lineages evolved phage resistance through elevated mucoidy, and during subsequent evolution in phage-free conditions they rapidly reverted to nonmucoid, phage-susceptible phenotypes. Genome sequencing revealed that this phenotypic reversion was achieved by additional genetic changes rather than by genotypic reversion of the initial resistance mutations. Insertion sequence (IS) elements played a key role in both the acquisition of resistance and adaptation in the absence of parasites; unlike single nucleotide polymorphisms, IS insertions were not more frequent in mutator lineages. Our results provide a genetic explanation for rapid reversion of mucoidy, a phenotype observed in other bacterial species including human pathogens. Moreover, this demonstrates that the types of genetic change underlying adaptation to fitness costs, and consequently the impact of evolvability mechanisms such as increased point-mutation rates, depend critically on the mechanism of resistance."}],"type":"journal_article","date_published":"2016-03-01T00:00:00Z","page":"770-782","citation":{"ieee":"S. Wielgoss, T. Bergmiller, A. M. Bischofberger, and A. R. Hall, “Adaptation to parasites and costs of parasite resistance in mutator and nonmutator bacteria,” Molecular Biology and Evolution, vol. 33, no. 3. Oxford University Press, pp. 770–782, 2016.","apa":"Wielgoss, S., Bergmiller, T., Bischofberger, A. M., & Hall, A. R. (2016). Adaptation to parasites and costs of parasite resistance in mutator and nonmutator bacteria. Molecular Biology and Evolution. Oxford University Press. https://doi.org/10.1093/molbev/msv270","ista":"Wielgoss S, Bergmiller T, Bischofberger AM, Hall AR. 2016. Adaptation to parasites and costs of parasite resistance in mutator and nonmutator bacteria. Molecular Biology and Evolution. 33(3), 770–782.","ama":"Wielgoss S, Bergmiller T, Bischofberger AM, Hall AR. Adaptation to parasites and costs of parasite resistance in mutator and nonmutator bacteria. Molecular Biology and Evolution. 2016;33(3):770-782. doi:10.1093/molbev/msv270","chicago":"Wielgoss, Sébastien, Tobias Bergmiller, Anna M. Bischofberger, and Alex R. Hall. “Adaptation to Parasites and Costs of Parasite Resistance in Mutator and Nonmutator Bacteria.” Molecular Biology and Evolution. Oxford University Press, 2016. https://doi.org/10.1093/molbev/msv270.","short":"S. Wielgoss, T. Bergmiller, A.M. Bischofberger, A.R. Hall, Molecular Biology and Evolution 33 (2016) 770–782.","mla":"Wielgoss, Sébastien, et al. “Adaptation to Parasites and Costs of Parasite Resistance in Mutator and Nonmutator Bacteria.” Molecular Biology and Evolution, vol. 33, no. 3, Oxford University Press, 2016, pp. 770–82, doi:10.1093/molbev/msv270."},"publication":"Molecular Biology and Evolution","article_processing_charge":"No","has_accepted_license":"1","day":"01","scopus_import":"1"},{"file_date_updated":"2018-12-12T10:11:39Z","ec_funded":1,"publist_id":"6283","article_number":"20","author":[{"id":"49351290-F248-11E8-B48F-1D18A9856A87","last_name":"Daca","first_name":"Przemyslaw","full_name":"Daca, Przemyslaw"},{"full_name":"Henzinger, Thomas A","first_name":"Thomas A","last_name":"Henzinger","id":"40876CD8-F248-11E8-B48F-1D18A9856A87","orcid":"0000−0002−2985−7724"},{"full_name":"Kretinsky, Jan","id":"44CEF464-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8122-2881","first_name":"Jan","last_name":"Kretinsky"},{"full_name":"Petrov, Tatjana","id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9041-0905","first_name":"Tatjana","last_name":"Petrov"}],"related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"1155"}]},"date_created":"2018-12-11T11:50:06Z","date_updated":"2023-09-07T11:58:33Z","volume":59,"year":"2016","acknowledgement":"This research was funded in part by the European Research Council (ERC) under grant agreement 267989\r\n(QUAREM), the Austrian Science Fund (FWF) under grants project S11402-N23 (RiSE and SHiNE)\r\nand Z211-N23 (Wittgenstein Award), by the Czech Science Foundation Grant No. P202/12/G061, and\r\nby the SNSF Advanced Postdoc. Mobility Fellowship – grant number P300P2_161067.","publication_status":"published","department":[{"_id":"ToHe"},{"_id":"KrCh"},{"_id":"CaGu"}],"publisher":"Schloss Dagstuhl - Leibniz-Zentrum für Informatik","month":"08","conference":{"start_date":"2016-08-23","location":"Quebec City; Canada","end_date":"2016-08-26","name":"CONCUR: Concurrency Theory"},"doi":"10.4230/LIPIcs.CONCUR.2016.20","language":[{"iso":"eng"}],"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"quality_controlled":"1","project":[{"call_identifier":"FP7","name":"Quantitative Reactive Modeling","grant_number":"267989","_id":"25EE3708-B435-11E9-9278-68D0E5697425"},{"name":"Rigorous Systems Engineering","call_identifier":"FWF","_id":"25832EC2-B435-11E9-9278-68D0E5697425","grant_number":"S 11407_N23"},{"call_identifier":"FWF","name":"The Wittgenstein Prize","_id":"25F42A32-B435-11E9-9278-68D0E5697425","grant_number":"Z211"}],"abstract":[{"lang":"eng","text":"We introduce a general class of distances (metrics) between Markov chains, which are based on linear behaviour. This class encompasses distances given topologically (such as the total variation distance or trace distance) as well as by temporal logics or automata. We investigate which of the distances can be approximated by observing the systems, i.e. by black-box testing or simulation, and we provide both negative and positive results. "}],"type":"conference","alternative_title":["LIPIcs"],"pubrep_id":"794","oa_version":"Published Version","file":[{"file_id":"4895","relation":"main_file","date_created":"2018-12-12T10:11:39Z","date_updated":"2018-12-12T10:11:39Z","file_name":"IST-2017-794-v1+1_LIPIcs-CONCUR-2016-20.pdf","access_level":"open_access","creator":"system","content_type":"application/pdf","file_size":501827}],"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","_id":"1093","status":"public","ddc":["004"],"title":"Linear distances between Markov chains","intvolume":" 59","day":"01","has_accepted_license":"1","scopus_import":1,"date_published":"2016-08-01T00:00:00Z","citation":{"mla":"Daca, Przemyslaw, et al. Linear Distances between Markov Chains. Vol. 59, 20, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2016, doi:10.4230/LIPIcs.CONCUR.2016.20.","short":"P. Daca, T.A. Henzinger, J. Kretinsky, T. Petrov, in:, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2016.","chicago":"Daca, Przemyslaw, Thomas A Henzinger, Jan Kretinsky, and Tatjana Petrov. “Linear Distances between Markov Chains,” Vol. 59. Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2016. https://doi.org/10.4230/LIPIcs.CONCUR.2016.20.","ama":"Daca P, Henzinger TA, Kretinsky J, Petrov T. Linear distances between Markov chains. In: Vol 59. Schloss Dagstuhl - Leibniz-Zentrum für Informatik; 2016. doi:10.4230/LIPIcs.CONCUR.2016.20","ista":"Daca P, Henzinger TA, Kretinsky J, Petrov T. 2016. Linear distances between Markov chains. CONCUR: Concurrency Theory, LIPIcs, vol. 59, 20.","ieee":"P. Daca, T. A. Henzinger, J. Kretinsky, and T. Petrov, “Linear distances between Markov chains,” presented at the CONCUR: Concurrency Theory, Quebec City; Canada, 2016, vol. 59.","apa":"Daca, P., Henzinger, T. A., Kretinsky, J., & Petrov, T. (2016). Linear distances between Markov chains (Vol. 59). Presented at the CONCUR: Concurrency Theory, Quebec City; Canada: Schloss Dagstuhl - Leibniz-Zentrum für Informatik. https://doi.org/10.4230/LIPIcs.CONCUR.2016.20"}},{"month":"01","language":[{"iso":"eng"}],"conference":{"name":"TACAS: Tools and Algorithms for the Construction and Analysis of Systems","start_date":"2016-04-02","location":"Eindhoven, The Netherlands","end_date":"2016-04-08"},"doi":"10.1007/978-3-662-49674-9_7","quality_controlled":"1","project":[{"_id":"25EE3708-B435-11E9-9278-68D0E5697425","grant_number":"267989","name":"Quantitative Reactive Modeling","call_identifier":"FP7"},{"_id":"25832EC2-B435-11E9-9278-68D0E5697425","grant_number":"S 11407_N23","call_identifier":"FWF","name":"Rigorous Systems Engineering"},{"grant_number":"Z211","_id":"25F42A32-B435-11E9-9278-68D0E5697425","name":"The Wittgenstein Prize","call_identifier":"FWF"},{"name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425"}],"oa":1,"main_file_link":[{"open_access":"1","url":"https://arxiv.org/abs/1504.05739"}],"publist_id":"6099","ec_funded":1,"date_created":"2018-12-11T11:50:51Z","date_updated":"2023-09-07T11:58:33Z","volume":9636,"author":[{"full_name":"Daca, Przemyslaw","first_name":"Przemyslaw","last_name":"Daca","id":"49351290-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Henzinger","first_name":"Thomas A","orcid":"0000−0002−2985−7724","id":"40876CD8-F248-11E8-B48F-1D18A9856A87","full_name":"Henzinger, Thomas A"},{"first_name":"Jan","last_name":"Kretinsky","id":"44CEF464-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8122-2881","full_name":"Kretinsky, Jan"},{"id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9041-0905","first_name":"Tatjana","last_name":"Petrov","full_name":"Petrov, Tatjana"}],"related_material":{"record":[{"status":"public","relation":"later_version","id":"471"},{"relation":"dissertation_contains","status":"public","id":"1155"}]},"publication_status":"published","department":[{"_id":"ToHe"},{"_id":"CaGu"}],"publisher":"Springer","acknowledgement":"This research was funded in part by the European Research Council (ERC) under\r\ngrant agreement 267989 (QUAREM), the Austrian Science Fund (FWF) under\r\ngrants project S11402-N23 (RiSE) and Z211-N23 (Wittgenstein Award), the Peo-\r\nple Programme (Marie Curie Actions) of the European Union’s Seventh Framework\r\nProgramme (FP7/2007-2013) REA Grant No 291734, the SNSF Advanced Postdoc.\r\nMobility Fellowship – grant number P300P2\r\n161067, and the Czech Science Foun-\r\ndation under grant agreement P202/12/G061.","year":"2016","day":"01","scopus_import":1,"date_published":"2016-01-01T00:00:00Z","page":"112 - 129","citation":{"ista":"Daca P, Henzinger TA, Kretinsky J, Petrov T. 2016. Faster statistical model checking for unbounded temporal properties. TACAS: Tools and Algorithms for the Construction and Analysis of Systems, LNCS, vol. 9636, 112–129.","ieee":"P. Daca, T. A. Henzinger, J. Kretinsky, and T. Petrov, “Faster statistical model checking for unbounded temporal properties,” presented at the TACAS: Tools and Algorithms for the Construction and Analysis of Systems, Eindhoven, The Netherlands, 2016, vol. 9636, pp. 112–129.","apa":"Daca, P., Henzinger, T. A., Kretinsky, J., & Petrov, T. (2016). Faster statistical model checking for unbounded temporal properties (Vol. 9636, pp. 112–129). Presented at the TACAS: Tools and Algorithms for the Construction and Analysis of Systems, Eindhoven, The Netherlands: Springer. https://doi.org/10.1007/978-3-662-49674-9_7","ama":"Daca P, Henzinger TA, Kretinsky J, Petrov T. Faster statistical model checking for unbounded temporal properties. In: Vol 9636. Springer; 2016:112-129. doi:10.1007/978-3-662-49674-9_7","chicago":"Daca, Przemyslaw, Thomas A Henzinger, Jan Kretinsky, and Tatjana Petrov. “Faster Statistical Model Checking for Unbounded Temporal Properties,” 9636:112–29. Springer, 2016. https://doi.org/10.1007/978-3-662-49674-9_7.","mla":"Daca, Przemyslaw, et al. Faster Statistical Model Checking for Unbounded Temporal Properties. Vol. 9636, Springer, 2016, pp. 112–29, doi:10.1007/978-3-662-49674-9_7.","short":"P. Daca, T.A. Henzinger, J. Kretinsky, T. Petrov, in:, Springer, 2016, pp. 112–129."},"abstract":[{"text":"We present a new algorithm for the statistical model checking of Markov chains with respect to unbounded temporal properties, including full linear temporal logic. The main idea is that we monitor each simulation run on the fly, in order to detect quickly if a bottom strongly connected component is entered with high probability, in which case the simulation run can be terminated early. As a result, our simulation runs are often much shorter than required by termination bounds that are computed a priori for a desired level of confidence on a large state space. In comparison to previous algorithms for statistical model checking our method is not only faster in many cases but also requires less information about the system, namely, only the minimum transition probability that occurs in the Markov chain. In addition, our method can be generalised to unbounded quantitative properties such as mean-payoff bounds.","lang":"eng"}],"alternative_title":["LNCS"],"type":"conference","oa_version":"Preprint","title":"Faster statistical model checking for unbounded temporal properties","status":"public","intvolume":" 9636","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","_id":"1234"},{"abstract":[{"text":"Restriction-modification (RM) systems represent a minimal and ubiquitous biological system of self/non-self discrimination in prokaryotes [1], which protects hosts from exogenous DNA [2]. The mechanism is based on the balance between methyltransferase (M) and cognate restriction endonuclease (R). M tags endogenous DNA as self by methylating short specific DNA sequences called restriction sites, whereas R recognizes unmethylated restriction sites as non-self and introduces a double-stranded DNA break [3]. Restriction sites are significantly underrepresented in prokaryotic genomes [4-7], suggesting that the discrimination mechanism is imperfect and occasionally leads to autoimmunity due to self-DNA cleavage (self-restriction) [8]. Furthermore, RM systems can promote DNA recombination [9] and contribute to genetic variation in microbial populations, thus facilitating adaptive evolution [10]. However, cleavage of self-DNA by RM systems as elements shaping prokaryotic genomes has not been directly detected, and its cause, frequency, and outcome are unknown. We quantify self-restriction caused by two RM systems of Escherichia coli and find that, in agreement with levels of restriction site avoidance, EcoRI, but not EcoRV, cleaves self-DNA at a measurable rate. Self-restriction is a stochastic process, which temporarily induces the SOS response, and is followed by DNA repair, maintaining cell viability. We find that RM systems with higher restriction efficiency against bacteriophage infections exhibit a higher rate of self-restriction, and that this rate can be further increased by stochastic imbalance between R and M. Our results identify molecular noise in RM systems as a factor shaping prokaryotic genomes.","lang":"eng"}],"issue":"3","type":"journal_article","oa_version":"None","status":"public","title":"Bacterial autoimmunity due to a restriction-modification system","intvolume":" 26","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","_id":"1243","day":"08","scopus_import":1,"date_published":"2016-02-08T00:00:00Z","page":"404 - 409","publication":"Current Biology","citation":{"apa":"Pleska, M., Qian, L., Okura, R., Bergmiller, T., Wakamoto, Y., Kussell, E., & Guet, C. C. (2016). Bacterial autoimmunity due to a restriction-modification system. Current Biology. Cell Press. https://doi.org/10.1016/j.cub.2015.12.041","ieee":"M. Pleska et al., “Bacterial autoimmunity due to a restriction-modification system,” Current Biology, vol. 26, no. 3. Cell Press, pp. 404–409, 2016.","ista":"Pleska M, Qian L, Okura R, Bergmiller T, Wakamoto Y, Kussell E, Guet CC. 2016. Bacterial autoimmunity due to a restriction-modification system. Current Biology. 26(3), 404–409.","ama":"Pleska M, Qian L, Okura R, et al. Bacterial autoimmunity due to a restriction-modification system. Current Biology. 2016;26(3):404-409. doi:10.1016/j.cub.2015.12.041","chicago":"Pleska, Maros, Long Qian, Reiko Okura, Tobias Bergmiller, Yuichi Wakamoto, Edo Kussell, and Calin C Guet. “Bacterial Autoimmunity Due to a Restriction-Modification System.” Current Biology. Cell Press, 2016. https://doi.org/10.1016/j.cub.2015.12.041.","short":"M. Pleska, L. Qian, R. Okura, T. Bergmiller, Y. Wakamoto, E. Kussell, C.C. Guet, Current Biology 26 (2016) 404–409.","mla":"Pleska, Maros, et al. “Bacterial Autoimmunity Due to a Restriction-Modification System.” Current Biology, vol. 26, no. 3, Cell Press, 2016, pp. 404–09, doi:10.1016/j.cub.2015.12.041."},"publist_id":"6087","date_created":"2018-12-11T11:50:54Z","date_updated":"2023-09-07T11:59:32Z","volume":26,"author":[{"last_name":"Pleska","first_name":"Maros","orcid":"0000-0001-7460-7479","id":"4569785E-F248-11E8-B48F-1D18A9856A87","full_name":"Pleska, Maros"},{"last_name":"Qian","first_name":"Long","full_name":"Qian, Long"},{"first_name":"Reiko","last_name":"Okura","full_name":"Okura, Reiko"},{"last_name":"Bergmiller","first_name":"Tobias","orcid":"0000-0001-5396-4346","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","full_name":"Bergmiller, Tobias"},{"last_name":"Wakamoto","first_name":"Yuichi","full_name":"Wakamoto, Yuichi"},{"first_name":"Edo","last_name":"Kussell","full_name":"Kussell, Edo"},{"last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C"}],"related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"202"}]},"publication_status":"published","publisher":"Cell Press","department":[{"_id":"CaGu"}],"acknowledgement":"This work was funded by an HFSP Young Investigators’ grant. M.P. is a recipient of a DOC Fellowship of the Austrian Academy of Science at the Institute of Science and Technology Austria. R.O. and Y.W. were supported by the Platform for Dynamic Approaches to Living System from MEXT, Japan. We wish to thank I. Kobayashi for providing us with the EcoRI and EcoRV plasmids, and A. Campbell for providing us with the λ vir phage. We thank D. Siekhaus and C. Uhler and members of the C.C.G. and J.P. Bollback laboratories for in-depth discussions. We thank B. Stern for comments on an earlier version of the manuscript. We especially thank B.R. Levin for advice and comments, and the anonymous reviewers for significantly improving the manuscript.","year":"2016","month":"02","language":[{"iso":"eng"}],"doi":"10.1016/j.cub.2015.12.041","quality_controlled":"1","project":[{"_id":"251D65D8-B435-11E9-9278-68D0E5697425","grant_number":"24210","name":"Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level (DOC Fellowship)"}]},{"related_material":{"record":[{"id":"6071","status":"public","relation":"dissertation_contains"}]},"author":[{"last_name":"Friedlander","first_name":"Tamar","id":"36A5845C-F248-11E8-B48F-1D18A9856A87","full_name":"Friedlander, Tamar"},{"full_name":"Prizak, Roshan","first_name":"Roshan","last_name":"Prizak","id":"4456104E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Guet, Calin C","last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-8548-5240","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","last_name":"Barton","first_name":"Nicholas H","full_name":"Barton, Nicholas H"},{"full_name":"Tkacik, Gasper","last_name":"Tkacik","first_name":"Gasper","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"}],"volume":7,"date_updated":"2023-09-07T12:53:49Z","date_created":"2018-12-11T11:51:34Z","year":"2016","department":[{"_id":"GaTk"},{"_id":"NiBa"},{"_id":"CaGu"}],"publisher":"Nature Publishing Group","publication_status":"published","publist_id":"5887","ec_funded":1,"file_date_updated":"2020-07-14T12:44:46Z","article_number":"12307","doi":"10.1038/ncomms12307","language":[{"iso":"eng"}],"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"project":[{"name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734"},{"call_identifier":"FP7","name":"Limits to selection in biology and in evolutionary computation","_id":"25B07788-B435-11E9-9278-68D0E5697425","grant_number":"250152"},{"call_identifier":"FWF","name":"Biophysics of information processing in gene regulation","_id":"254E9036-B435-11E9-9278-68D0E5697425","grant_number":"P28844-B27"}],"quality_controlled":"1","month":"08","pubrep_id":"627","oa_version":"Published Version","file":[{"creator":"system","file_size":861805,"content_type":"application/pdf","access_level":"open_access","file_name":"IST-2016-627-v1+1_ncomms12307.pdf","checksum":"fe3f3a1526d180b29fe691ab11435b78","date_updated":"2020-07-14T12:44:46Z","date_created":"2018-12-12T10:12:01Z","file_id":"4919","relation":"main_file"},{"date_created":"2018-12-12T10:12:02Z","date_updated":"2020-07-14T12:44:46Z","checksum":"164864a1a675f3ad80e9917c27aba07f","file_id":"4920","relation":"main_file","creator":"system","content_type":"application/pdf","file_size":1084703,"file_name":"IST-2016-627-v1+2_ncomms12307-s1.pdf","access_level":"open_access"}],"_id":"1358","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","intvolume":" 7","title":"Intrinsic limits to gene regulation by global crosstalk","status":"public","ddc":["576"],"abstract":[{"lang":"eng","text":"Gene regulation relies on the specificity of transcription factor (TF)–DNA interactions. Limited specificity may lead to crosstalk: a regulatory state in which a gene is either incorrectly activated due to noncognate TF–DNA interactions or remains erroneously inactive. As each TF can have numerous interactions with noncognate cis-regulatory elements, crosstalk is inherently a global problem, yet has previously not been studied as such. We construct a theoretical framework to analyse the effects of global crosstalk on gene regulation. We find that crosstalk presents a significant challenge for organisms with low-specificity TFs, such as metazoans. Crosstalk is not easily mitigated by known regulatory schemes acting at equilibrium, including variants of cooperativity and combinatorial regulation. Our results suggest that crosstalk imposes a previously unexplored global constraint on the functioning and evolution of regulatory networks, which is qualitatively distinct from the known constraints that act at the level of individual gene regulatory elements."}],"type":"journal_article","date_published":"2016-08-04T00:00:00Z","citation":{"apa":"Friedlander, T., Prizak, R., Guet, C. C., Barton, N. H., & Tkačik, G. (2016). Intrinsic limits to gene regulation by global crosstalk. Nature Communications. Nature Publishing Group. https://doi.org/10.1038/ncomms12307","ieee":"T. Friedlander, R. Prizak, C. C. Guet, N. H. Barton, and G. Tkačik, “Intrinsic limits to gene regulation by global crosstalk,” Nature Communications, vol. 7. Nature Publishing Group, 2016.","ista":"Friedlander T, Prizak R, Guet CC, Barton NH, Tkačik G. 2016. Intrinsic limits to gene regulation by global crosstalk. Nature Communications. 7, 12307.","ama":"Friedlander T, Prizak R, Guet CC, Barton NH, Tkačik G. Intrinsic limits to gene regulation by global crosstalk. Nature Communications. 2016;7. doi:10.1038/ncomms12307","chicago":"Friedlander, Tamar, Roshan Prizak, Calin C Guet, Nicholas H Barton, and Gašper Tkačik. “Intrinsic Limits to Gene Regulation by Global Crosstalk.” Nature Communications. Nature Publishing Group, 2016. https://doi.org/10.1038/ncomms12307.","short":"T. Friedlander, R. Prizak, C.C. Guet, N.H. Barton, G. Tkačik, Nature Communications 7 (2016).","mla":"Friedlander, Tamar, et al. “Intrinsic Limits to Gene Regulation by Global Crosstalk.” Nature Communications, vol. 7, 12307, Nature Publishing Group, 2016, doi:10.1038/ncomms12307."},"publication":"Nature Communications","has_accepted_license":"1","day":"04","scopus_import":1},{"scopus_import":1,"day":"11","month":"07","publication":"Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation","oa":1,"citation":{"ama":"Paixao T, Sudholt D, Heredia J, Trubenova B. First steps towards a runtime comparison of natural and artificial evolution. In: Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation. ACM; 2015:1455-1462. doi:10.1145/2739480.2754758","apa":"Paixao, T., Sudholt, D., Heredia, J., & Trubenova, B. (2015). First steps towards a runtime comparison of natural and artificial evolution. In Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation (pp. 1455–1462). Madrid, Spain: ACM. https://doi.org/10.1145/2739480.2754758","ieee":"T. Paixao, D. Sudholt, J. Heredia, and B. Trubenova, “First steps towards a runtime comparison of natural and artificial evolution,” in Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation, Madrid, Spain, 2015, pp. 1455–1462.","ista":"Paixao T, Sudholt D, Heredia J, Trubenova B. 2015. First steps towards a runtime comparison of natural and artificial evolution. Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation. GECCO: Genetic and evolutionary computation conference, 1455–1462.","short":"T. Paixao, D. Sudholt, J. Heredia, B. Trubenova, in:, Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation, ACM, 2015, pp. 1455–1462.","mla":"Paixao, Tiago, et al. “First Steps towards a Runtime Comparison of Natural and Artificial Evolution.” Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation, ACM, 2015, pp. 1455–62, doi:10.1145/2739480.2754758.","chicago":"Paixao, Tiago, Dirk Sudholt, Jorge Heredia, and Barbora Trubenova. “First Steps towards a Runtime Comparison of Natural and Artificial Evolution.” In Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation, 1455–62. ACM, 2015. https://doi.org/10.1145/2739480.2754758."},"main_file_link":[{"open_access":"1","url":"http://arxiv.org/abs/1504.06260"}],"quality_controlled":"1","page":"1455 - 1462","project":[{"_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","grant_number":"618091","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","call_identifier":"FP7"}],"conference":{"end_date":"2015-07-15","start_date":"2015-07-11","location":"Madrid, Spain","name":"GECCO: Genetic and evolutionary computation conference"},"doi":"10.1145/2739480.2754758","date_published":"2015-07-11T00:00:00Z","language":[{"iso":"eng"}],"type":"conference","abstract":[{"lang":"eng","text":"Evolutionary algorithms (EAs) form a popular optimisation paradigm inspired by natural evolution. In recent years the field of evolutionary computation has developed a rigorous analytical theory to analyse their runtime on many illustrative problems. Here we apply this theory to a simple model of natural evolution. In the Strong Selection Weak Mutation (SSWM) evolutionary regime the time between occurrence of new mutations is much longer than the time it takes for a new beneficial mutation to take over the population. In this situation, the population only contains copies of one genotype and evolution can be modelled as a (1+1)-type process where the probability of accepting a new genotype (improvements or worsenings) depends on the change in fitness. We present an initial runtime analysis of SSWM, quantifying its performance for various parameters and investigating differences to the (1+1) EA. We show that SSWM can have a moderate advantage over the (1+1) EA at crossing fitness valleys and study an example where SSWM outperforms the (1+1) EA by taking advantage of information on the fitness gradient."}],"ec_funded":1,"publist_id":"5768","_id":"1430","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","year":"2015","status":"public","publication_status":"published","title":"First steps towards a runtime comparison of natural and artificial evolution","department":[{"_id":"NiBa"},{"_id":"CaGu"}],"publisher":"ACM","author":[{"last_name":"Paixao","first_name":"Tiago","orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","full_name":"Paixao, Tiago"},{"full_name":"Sudholt, Dirk","first_name":"Dirk","last_name":"Sudholt"},{"full_name":"Heredia, Jorge","last_name":"Heredia","first_name":"Jorge"},{"last_name":"Trubenova","first_name":"Barbora","orcid":"0000-0002-6873-2967","id":"42302D54-F248-11E8-B48F-1D18A9856A87","full_name":"Trubenova, Barbora"}],"date_created":"2018-12-11T11:51:58Z","date_updated":"2021-01-12T06:50:41Z","oa_version":"Preprint"},{"has_accepted_license":"1","day":"21","scopus_import":1,"date_published":"2015-10-21T00:00:00Z","citation":{"ama":"Paixao T, Badkobeh G, Barton NH, et al. Toward a unifying framework for evolutionary processes. Journal of Theoretical Biology. 2015;383:28-43. doi:10.1016/j.jtbi.2015.07.011","ista":"Paixao T, Badkobeh G, Barton NH, Çörüş D, Dang D, Friedrich T, Lehre P, Sudholt D, Sutton A, Trubenova B. 2015. Toward a unifying framework for evolutionary processes. Journal of Theoretical Biology. 383, 28–43.","ieee":"T. Paixao et al., “Toward a unifying framework for evolutionary processes,” Journal of Theoretical Biology, vol. 383. Elsevier, pp. 28–43, 2015.","apa":"Paixao, T., Badkobeh, G., Barton, N. H., Çörüş, D., Dang, D., Friedrich, T., … Trubenova, B. (2015). Toward a unifying framework for evolutionary processes. Journal of Theoretical Biology. Elsevier. https://doi.org/10.1016/j.jtbi.2015.07.011","mla":"Paixao, Tiago, et al. “Toward a Unifying Framework for Evolutionary Processes.” Journal of Theoretical Biology, vol. 383, Elsevier, 2015, pp. 28–43, doi:10.1016/j.jtbi.2015.07.011.","short":"T. Paixao, G. Badkobeh, N.H. Barton, D. Çörüş, D. Dang, T. Friedrich, P. Lehre, D. Sudholt, A. Sutton, B. Trubenova, Journal of Theoretical Biology 383 (2015) 28–43.","chicago":"Paixao, Tiago, Golnaz Badkobeh, Nicholas H Barton, Doğan Çörüş, Duccuong Dang, Tobias Friedrich, Per Lehre, Dirk Sudholt, Andrew Sutton, and Barbora Trubenova. “Toward a Unifying Framework for Evolutionary Processes.” Journal of Theoretical Biology. Elsevier, 2015. https://doi.org/10.1016/j.jtbi.2015.07.011."},"publication":" Journal of Theoretical Biology","page":"28 - 43","abstract":[{"text":"The theory of population genetics and evolutionary computation have been evolving separately for nearly 30 years. Many results have been independently obtained in both fields and many others are unique to its respective field. We aim to bridge this gap by developing a unifying framework for evolutionary processes that allows both evolutionary algorithms and population genetics models to be cast in the same formal framework. The framework we present here decomposes the evolutionary process into its several components in order to facilitate the identification of similarities between different models. In particular, we propose a classification of evolutionary operators based on the defining properties of the different components. We cast several commonly used operators from both fields into this common framework. Using this, we map different evolutionary and genetic algorithms to different evolutionary regimes and identify candidates with the most potential for the translation of results between the fields. This provides a unified description of evolutionary processes and represents a stepping stone towards new tools and results to both fields. ","lang":"eng"}],"type":"journal_article","pubrep_id":"483","file":[{"file_name":"IST-2016-483-v1+1_1-s2.0-S0022519315003409-main.pdf","access_level":"open_access","creator":"system","file_size":595307,"content_type":"application/pdf","file_id":"5244","relation":"main_file","date_created":"2018-12-12T10:16:53Z","date_updated":"2020-07-14T12:45:01Z","checksum":"33b60ecfea60764756a9ee9df5eb65ca"}],"oa_version":"Published Version","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"1542","intvolume":" 383","ddc":["570"],"status":"public","title":"Toward a unifying framework for evolutionary processes","month":"10","doi":"10.1016/j.jtbi.2015.07.011","language":[{"iso":"eng"}],"oa":1,"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"project":[{"name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","call_identifier":"FP7","grant_number":"618091","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FP7","name":"Limits to selection in biology and in evolutionary computation","grant_number":"250152","_id":"25B07788-B435-11E9-9278-68D0E5697425"}],"quality_controlled":"1","publist_id":"5629","ec_funded":1,"file_date_updated":"2020-07-14T12:45:01Z","author":[{"full_name":"Paixao, Tiago","orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","last_name":"Paixao","first_name":"Tiago"},{"full_name":"Badkobeh, Golnaz","first_name":"Golnaz","last_name":"Badkobeh"},{"id":"4880FE40-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8548-5240","first_name":"Nicholas H","last_name":"Barton","full_name":"Barton, Nicholas H"},{"full_name":"Çörüş, Doğan","last_name":"Çörüş","first_name":"Doğan"},{"last_name":"Dang","first_name":"Duccuong","full_name":"Dang, Duccuong"},{"full_name":"Friedrich, Tobias","first_name":"Tobias","last_name":"Friedrich"},{"last_name":"Lehre","first_name":"Per","full_name":"Lehre, Per"},{"full_name":"Sudholt, Dirk","last_name":"Sudholt","first_name":"Dirk"},{"full_name":"Sutton, Andrew","last_name":"Sutton","first_name":"Andrew"},{"full_name":"Trubenova, Barbora","id":"42302D54-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6873-2967","first_name":"Barbora","last_name":"Trubenova"}],"volume":383,"date_updated":"2021-01-12T06:51:29Z","date_created":"2018-12-11T11:52:37Z","year":"2015","publisher":"Elsevier","department":[{"_id":"NiBa"},{"_id":"CaGu"}],"publication_status":"published"},{"issue":"4","abstract":[{"lang":"eng","text":"In this paper, we present a method for reducing a regular, discrete-time Markov chain (DTMC) to another DTMC with a given, typically much smaller number of states. The cost of reduction is defined as the Kullback-Leibler divergence rate between a projection of the original process through a partition function and a DTMC on the correspondingly partitioned state space. Finding the reduced model with minimal cost is computationally expensive, as it requires an exhaustive search among all state space partitions, and an exact evaluation of the reduction cost for each candidate partition. Our approach deals with the latter problem by minimizing an upper bound on the reduction cost instead of minimizing the exact cost. The proposed upper bound is easy to compute and it is tight if the original chain is lumpable with respect to the partition. Then, we express the problem in the form of information bottleneck optimization, and propose using the agglomerative information bottleneck algorithm for searching a suboptimal partition greedily, rather than exhaustively. The theory is illustrated with examples and one application scenario in the context of modeling bio-molecular interactions."}],"type":"journal_article","oa_version":"Preprint","intvolume":" 60","status":"public","title":"Optimal Kullback-Leibler aggregation via information bottleneck","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"1840","day":"01","scopus_import":1,"date_published":"2015-04-01T00:00:00Z","page":"1010 - 1022","citation":{"chicago":"Geiger, Bernhard, Tatjana Petrov, Gernot Kubin, and Heinz Koeppl. “Optimal Kullback-Leibler Aggregation via Information Bottleneck.” IEEE Transactions on Automatic Control. IEEE, 2015. https://doi.org/10.1109/TAC.2014.2364971.","short":"B. Geiger, T. Petrov, G. Kubin, H. Koeppl, IEEE Transactions on Automatic Control 60 (2015) 1010–1022.","mla":"Geiger, Bernhard, et al. “Optimal Kullback-Leibler Aggregation via Information Bottleneck.” IEEE Transactions on Automatic Control, vol. 60, no. 4, IEEE, 2015, pp. 1010–22, doi:10.1109/TAC.2014.2364971.","ieee":"B. Geiger, T. Petrov, G. Kubin, and H. Koeppl, “Optimal Kullback-Leibler aggregation via information bottleneck,” IEEE Transactions on Automatic Control, vol. 60, no. 4. IEEE, pp. 1010–1022, 2015.","apa":"Geiger, B., Petrov, T., Kubin, G., & Koeppl, H. (2015). Optimal Kullback-Leibler aggregation via information bottleneck. IEEE Transactions on Automatic Control. IEEE. https://doi.org/10.1109/TAC.2014.2364971","ista":"Geiger B, Petrov T, Kubin G, Koeppl H. 2015. Optimal Kullback-Leibler aggregation via information bottleneck. IEEE Transactions on Automatic Control. 60(4), 1010–1022.","ama":"Geiger B, Petrov T, Kubin G, Koeppl H. Optimal Kullback-Leibler aggregation via information bottleneck. IEEE Transactions on Automatic Control. 2015;60(4):1010-1022. doi:10.1109/TAC.2014.2364971"},"publication":"IEEE Transactions on Automatic Control","publist_id":"5262","volume":60,"date_created":"2018-12-11T11:54:18Z","date_updated":"2021-01-12T06:53:33Z","author":[{"full_name":"Geiger, Bernhard","last_name":"Geiger","first_name":"Bernhard"},{"orcid":"0000-0002-9041-0905","id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","last_name":"Petrov","first_name":"Tatjana","full_name":"Petrov, Tatjana"},{"last_name":"Kubin","first_name":"Gernot","full_name":"Kubin, Gernot"},{"full_name":"Koeppl, Heinz","first_name":"Heinz","last_name":"Koeppl"}],"department":[{"_id":"CaGu"},{"_id":"ToHe"}],"publisher":"IEEE","publication_status":"published","year":"2015","acknowledgement":"This work was supported by the Austrian Research Association under Project 06/12684, by the Swiss National Science Foundation (SNSF) under Grant PP00P2 128503/1, by the SystemsX.ch (the Swiss Inititative for Systems Biology), and by a SNSF Early Postdoc.Mobility Fellowship grant P2EZP2_148797.\r\n","publication_identifier":{"issn":["0018-9286"]},"month":"04","language":[{"iso":"eng"}],"doi":"10.1109/TAC.2014.2364971","quality_controlled":"1","oa":1,"main_file_link":[{"open_access":"1","url":"http://arxiv.org/abs/1304.6603"}]},{"status":"public","title":"Other fitness models for comparison & for interacting TFBSs","department":[{"_id":"NiBa"},{"_id":"CaGu"},{"_id":"GaTk"}],"publisher":"Public Library of Science","year":"2015","_id":"9712","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","date_created":"2021-07-23T12:00:37Z","date_updated":"2023-02-23T10:09:08Z","oa_version":"Published Version","author":[{"full_name":"Tugrul, Murat","id":"37C323C6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8523-0758","first_name":"Murat","last_name":"Tugrul"},{"full_name":"Paixao, Tiago","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2361-3953","first_name":"Tiago","last_name":"Paixao"},{"full_name":"Barton, Nicholas H","first_name":"Nicholas H","last_name":"Barton","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8548-5240"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","first_name":"Gašper","last_name":"Tkačik","full_name":"Tkačik, Gašper"}],"related_material":{"record":[{"id":"1666","relation":"used_in_publication","status":"public"}]},"type":"research_data_reference","citation":{"short":"M. Tugrul, T. Paixao, N.H. Barton, G. Tkačik, (2015).","mla":"Tugrul, Murat, et al. Other Fitness Models for Comparison & for Interacting TFBSs. Public Library of Science, 2015, doi:10.1371/journal.pgen.1005639.s001.","chicago":"Tugrul, Murat, Tiago Paixao, Nicholas H Barton, and Gašper Tkačik. “Other Fitness Models for Comparison & for Interacting TFBSs.” Public Library of Science, 2015. https://doi.org/10.1371/journal.pgen.1005639.s001.","ama":"Tugrul M, Paixao T, Barton NH, Tkačik G. Other fitness models for comparison & for interacting TFBSs. 2015. doi:10.1371/journal.pgen.1005639.s001","apa":"Tugrul, M., Paixao, T., Barton, N. H., & Tkačik, G. (2015). Other fitness models for comparison & for interacting TFBSs. Public Library of Science. https://doi.org/10.1371/journal.pgen.1005639.s001","ieee":"M. Tugrul, T. Paixao, N. H. Barton, and G. Tkačik, “Other fitness models for comparison & for interacting TFBSs.” Public Library of Science, 2015.","ista":"Tugrul M, Paixao T, Barton NH, Tkačik G. 2015. Other fitness models for comparison & for interacting TFBSs, Public Library of Science, 10.1371/journal.pgen.1005639.s001."},"date_published":"2015-11-06T00:00:00Z","doi":"10.1371/journal.pgen.1005639.s001","month":"11","day":"06","article_processing_charge":"No"},{"article_processing_charge":"No","day":"21","month":"12","oa":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.5061/dryad.cj910"}],"citation":{"chicago":"Wielgoss, Sébastien, Tobias Bergmiller, Anna M. Bischofberger, and Alex R. Hall. “Data from: Adaptation to Parasites and Costs of Parasite Resistance in Mutator and Non-Mutator Bacteria.” Dryad, 2015. https://doi.org/10.5061/dryad.cj910.","short":"S. Wielgoss, T. Bergmiller, A.M. Bischofberger, A.R. Hall, (2015).","mla":"Wielgoss, Sébastien, et al. Data from: Adaptation to Parasites and Costs of Parasite Resistance in Mutator and Non-Mutator Bacteria. Dryad, 2015, doi:10.5061/dryad.cj910.","apa":"Wielgoss, S., Bergmiller, T., Bischofberger, A. M., & Hall, A. R. (2015). Data from: Adaptation to parasites and costs of parasite resistance in mutator and non-mutator bacteria. Dryad. https://doi.org/10.5061/dryad.cj910","ieee":"S. Wielgoss, T. Bergmiller, A. M. Bischofberger, and A. R. Hall, “Data from: Adaptation to parasites and costs of parasite resistance in mutator and non-mutator bacteria.” Dryad, 2015.","ista":"Wielgoss S, Bergmiller T, Bischofberger AM, Hall AR. 2015. Data from: Adaptation to parasites and costs of parasite resistance in mutator and non-mutator bacteria, Dryad, 10.5061/dryad.cj910.","ama":"Wielgoss S, Bergmiller T, Bischofberger AM, Hall AR. Data from: Adaptation to parasites and costs of parasite resistance in mutator and non-mutator bacteria. 2015. doi:10.5061/dryad.cj910"},"date_published":"2015-12-21T00:00:00Z","doi":"10.5061/dryad.cj910","type":"research_data_reference","abstract":[{"lang":"eng","text":"Parasitism creates selection for resistance mechanisms in host populations and is hypothesized to promote increased host evolvability. However, the influence of these traits on host evolution when parasites are no longer present is unclear. We used experimental evolution and whole-genome sequencing of Escherichia coli to determine the effects of past and present exposure to parasitic viruses (phages) on the spread of mutator alleles, resistance, and bacterial competitive fitness. We found that mutator alleles spread rapidly during adaptation to any of four different phage species, and this pattern was even more pronounced with multiple phages present simultaneously. However, hypermutability did not detectably accelerate adaptation in the absence of phages and recovery of fitness costs associated with resistance. Several lineages evolved phage resistance through elevated mucoidy, and during subsequent evolution in phage-free conditions they rapidly reverted to nonmucoid, phage-susceptible phenotypes. Genome sequencing revealed that this phenotypic reversion was achieved by additional genetic changes rather than by genotypic reversion of the initial resistance mutations. Insertion sequence (IS) elements played a key role in both the acquisition of resistance and adaptation in the absence of parasites; unlike single nucleotide polymorphisms, IS insertions were not more frequent in mutator lineages. Our results provide a genetic explanation for rapid reversion of mucoidy, a phenotype observed in other bacterial species including human pathogens. Moreover, this demonstrates that the types of genetic change underlying adaptation to fitness costs, and consequently the impact of evolvability mechanisms such as increased point-mutation rates, depend critically on the mechanism of resistance."}],"publisher":"Dryad","department":[{"_id":"CaGu"}],"title":"Data from: Adaptation to parasites and costs of parasite resistance in mutator and non-mutator bacteria","status":"public","year":"2015","_id":"9719","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","oa_version":"Published Version","date_created":"2021-07-26T08:44:04Z","date_updated":"2023-09-05T13:46:04Z","related_material":{"record":[{"id":"5749","status":"public","relation":"used_in_publication"}]},"author":[{"full_name":"Wielgoss, Sébastien","first_name":"Sébastien","last_name":"Wielgoss"},{"full_name":"Bergmiller, Tobias","first_name":"Tobias","last_name":"Bergmiller","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5396-4346"},{"full_name":"Bischofberger, Anna M.","last_name":"Bischofberger","first_name":"Anna M."},{"full_name":"Hall, Alex R.","last_name":"Hall","first_name":"Alex R."}]}]