[{"file":[{"date_updated":"2020-07-14T12:47:10Z","file_name":"IST-2017-918-v1+1_elife-28921-figures-v3.pdf","content_type":"application/pdf","date_created":"2018-12-12T10:14:42Z","checksum":"273ab17f33305e4eaafd911ff88e7c5b","file_size":8453470,"file_id":"5096","creator":"system","access_level":"open_access","relation":"main_file"},{"access_level":"open_access","relation":"main_file","creator":"system","file_id":"5097","file_size":1953221,"checksum":"b433f90576c7be597cd43367946f8e7f","date_created":"2018-12-12T10:14:43Z","file_name":"IST-2017-918-v1+2_elife-28921-v3.pdf","content_type":"application/pdf","date_updated":"2020-07-14T12:47:10Z"}],"status":"public","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_identifier":{"issn":["2050084X"]},"oa":1,"publist_id":"7244","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"date_published":"2017-11-13T00:00:00Z","type":"journal_article","language":[{"iso":"eng"}],"oa_version":"Published Version","project":[{"grant_number":"291734","name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","_id":"2578D616-B435-11E9-9278-68D0E5697425","name":"Selective Barriers to Horizontal Gene Transfer","grant_number":"648440"}],"month":"11","article_number":"e28921","publication":"eLife","has_accepted_license":"1","volume":6,"ddc":["576"],"doi":"10.7554/eLife.28921","day":"13","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"}],"date_updated":"2021-01-12T08:03:15Z","citation":{"ista":"Lagator M, Sarikas S, Acar H, Bollback JP, Guet CC. 2017. Regulatory network structure determines patterns of intermolecular epistasis. eLife. 6, e28921.","mla":"Lagator, Mato, et al. “Regulatory Network Structure Determines Patterns of Intermolecular Epistasis.” ELife, vol. 6, e28921, eLife Sciences Publications, 2017, doi:10.7554/eLife.28921.","short":"M. Lagator, S. Sarikas, H. Acar, J.P. Bollback, C.C. Guet, ELife 6 (2017).","chicago":"Lagator, Mato, Srdjan Sarikas, Hande Acar, Jonathan P Bollback, and Calin C Guet. “Regulatory Network Structure Determines Patterns of Intermolecular Epistasis.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.28921.","ieee":"M. Lagator, S. Sarikas, H. Acar, J. P. Bollback, and C. C. Guet, “Regulatory network structure determines patterns of intermolecular epistasis,” eLife, vol. 6. eLife Sciences Publications, 2017.","apa":"Lagator, M., Sarikas, S., Acar, H., Bollback, J. P., & Guet, C. C. (2017). Regulatory network structure determines patterns of intermolecular epistasis. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.28921","ama":"Lagator M, Sarikas S, Acar H, Bollback JP, Guet CC. Regulatory network structure determines patterns of intermolecular epistasis. eLife. 2017;6. doi:10.7554/eLife.28921"},"year":"2017","publisher":"eLife Sciences Publications","quality_controlled":"1","ec_funded":1,"file_date_updated":"2020-07-14T12:47:10Z","publication_status":"published","department":[{"_id":"CaGu"},{"_id":"JoBo"},{"_id":"NiBa"}],"date_created":"2018-12-11T11:47:14Z","title":"Regulatory network structure determines patterns of intermolecular epistasis","pubrep_id":"918","intvolume":" 6","_id":"570","scopus_import":1,"author":[{"last_name":"Lagator","first_name":"Mato","full_name":"Lagator, Mato","id":"345D25EC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Sarikas, Srdjan","last_name":"Sarikas","first_name":"Srdjan","id":"35F0286E-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Acar","first_name":"Hande","full_name":"Acar, Hande","orcid":"0000-0003-1986-9753","id":"2DDF136A-F248-11E8-B48F-1D18A9856A87"},{"id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","last_name":"Bollback","first_name":"Jonathan P","full_name":"Bollback, Jonathan P","orcid":"0000-0002-4624-4612"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","first_name":"Calin C","last_name":"Guet"}]},{"abstract":[{"text":"Bacteria in groups vary individually, and interact with other bacteria and the environment to produce population-level patterns of gene expression. Investigating such behavior in detail requires measuring and controlling populations at the single-cell level alongside precisely specified interactions and environmental characteristics. Here we present an automated, programmable platform that combines image-based gene expression and growth measurements with on-line optogenetic expression control for hundreds of individual Escherichia coli cells over days, in a dynamically adjustable environment. This integrated platform broadly enables experiments that bridge individual and population behaviors. We demonstrate: (i) population structuring by independent closed-loop control of gene expression in many individual cells, (ii) cell-cell variation control during antibiotic perturbation, (iii) hybrid bio-digital circuits in single cells, and freely specifiable digital communication between individual bacteria. These examples showcase the potential for real-time integration of theoretical models with measurement and control of many individual cells to investigate and engineer microbial population behavior.","lang":"eng"}],"doi":"10.1038/s41467-017-01683-1","day":"01","date_updated":"2021-01-12T08:06:15Z","year":"2017","citation":{"short":"R.P. Chait, J. Ruess, T. Bergmiller, G. Tkačik, C.C. Guet, Nature Communications 8 (2017).","mla":"Chait, Remy P., et al. “Shaping Bacterial Population Behavior through Computer Interfaced Control of Individual Cells.” Nature Communications, vol. 8, no. 1, 1535, Nature Publishing Group, 2017, doi:10.1038/s41467-017-01683-1.","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.","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","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.","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."},"ddc":["576","579"],"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).","volume":8,"pubrep_id":"911","title":"Shaping bacterial population behavior through computer interfaced control of individual cells","intvolume":" 8","publication_status":"published","date_created":"2018-12-11T11:47:30Z","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"article_processing_charge":"Yes (in subscription journal)","author":[{"id":"3464AE84-F248-11E8-B48F-1D18A9856A87","last_name":"Chait","first_name":"Remy P","full_name":"Chait, Remy P","orcid":"0000-0003-0876-3187"},{"id":"4A245D00-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1615-3282","full_name":"Ruess, Jakob","first_name":"Jakob","last_name":"Ruess"},{"orcid":"0000-0001-5396-4346","full_name":"Bergmiller, Tobias","first_name":"Tobias","last_name":"Bergmiller","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Gasper","last_name":"Tkacik","orcid":"0000-0002-6699-1455","full_name":"Tkacik, Gasper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052"}],"issue":"1","_id":"613","scopus_import":1,"publisher":"Nature Publishing Group","file_date_updated":"2020-07-14T12:47:20Z","quality_controlled":"1","ec_funded":1,"publist_id":"7191","oa":1,"publication_identifier":{"issn":["20411723"]},"date_published":"2017-12-01T00:00:00Z","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"status":"public","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","file":[{"creator":"system","file_id":"5190","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"IST-2017-911-v1+1_s41467-017-01683-1.pdf","date_updated":"2020-07-14T12:47:20Z","checksum":"44bb5d0229926c23a9955d9fe0f9723f","file_size":1951699,"date_created":"2018-12-12T10:16:05Z"}],"month":"12","article_number":"1535","oa_version":"Published Version","project":[{"name":"International IST Postdoc Fellowship Programme","grant_number":"291734","call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425"},{"_id":"254E9036-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Biophysics of information processing in gene regulation","grant_number":"P28844-B27"}],"publication":"Nature Communications","has_accepted_license":"1","language":[{"iso":"eng"}]},{"has_accepted_license":"1","publication":"PeerJ","oa_version":"Published Version","article_number":"3830","month":"09","language":[{"iso":"eng"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"type":"journal_article","date_published":"2017-09-21T00:00:00Z","publication_identifier":{"issn":["21678359"]},"publist_id":"7172","oa":1,"file":[{"access_level":"open_access","relation":"main_file","creator":"system","file_id":"4908","checksum":"3d79ae6b6eabc90b0eaaed82ff3493b0","file_size":682064,"date_created":"2018-12-12T10:11:51Z","file_name":"IST-2017-909-v1+1_peerj-3830.pdf","content_type":"application/pdf","date_updated":"2020-07-14T12:47:24Z"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","scopus_import":1,"_id":"624","issue":"9","author":[{"first_name":"Nela","last_name":"Nikolic","orcid":"0000-0001-9068-6090","full_name":"Nikolic, Nela","id":"42D9CABC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Didara, Zrinka","first_name":"Zrinka","last_name":"Didara"},{"full_name":"Moll, Isabella","first_name":"Isabella","last_name":"Moll"}],"date_created":"2018-12-11T11:47:33Z","department":[{"_id":"CaGu"}],"publication_status":"published","intvolume":" 2017","pubrep_id":"909","title":"MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations","quality_controlled":"1","file_date_updated":"2020-07-14T12:47:24Z","publisher":"PeerJ","year":"2017","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.","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","ista":"Nikolic N, Didara Z, Moll I. 2017. MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations. PeerJ. 2017(9), 3830.","short":"N. Nikolic, Z. Didara, I. Moll, PeerJ 2017 (2017).","mla":"Nikolic, Nela, et al. “MazF Activation Promotes Translational Heterogeneity of the GrcA MRNA in Escherichia Coli Populations.” PeerJ, vol. 2017, no. 9, 3830, PeerJ, 2017, doi:10.7717/peerj.3830."},"date_updated":"2021-01-12T08:06:48Z","day":"21","doi":"10.7717/peerj.3830","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."}],"volume":2017,"acknowledgement":"Austrian Science Fund (FWF): M1697, P22249; Swiss National Science Foundation (SNF): 145706; European Commission;FWF Special Research Program: RNA-REG F43","ddc":["579"]},{"file":[{"relation":"main_file","access_level":"open_access","file_id":"4716","creator":"system","date_created":"2018-12-12T10:08:53Z","file_size":5520359,"checksum":"39e1c3e82ddac83a30422fa72fa1a383","date_updated":"2020-07-14T12:47:33Z","file_name":"IST-2017-904-v1+1_elife-23136-v2.pdf","content_type":"application/pdf"},{"date_created":"2018-12-12T10:08:54Z","checksum":"a6d542253028f52e00aa29739ddffe8f","file_size":11242920,"date_updated":"2020-07-14T12:47:33Z","file_name":"IST-2017-904-v1+2_elife-23136-figures-v2.pdf","content_type":"application/pdf","access_level":"open_access","relation":"main_file","file_id":"4717","creator":"system"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"date_published":"2017-03-06T00:00:00Z","type":"journal_article","publication_identifier":{"issn":["2050084X"]},"oa":1,"publist_id":"7082","language":[{"iso":"eng"}],"publication":"eLife","has_accepted_license":"1","oa_version":"Published Version","month":"03","article_number":"e23136","volume":6,"ddc":["579"],"date_updated":"2021-01-12T08:07:55Z","citation":{"chicago":"Renault, Thibaud, Anthony Abraham, Tobias Bergmiller, Guillaume Paradis, Simon Rainville, Emmanuelle Charpentier, Calin C Guet, et al. “Bacterial Flagella Grow through an Injection Diffusion Mechanism.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.23136.","ieee":"T. Renault et al., “Bacterial flagella grow through an injection diffusion mechanism,” eLife, vol. 6. eLife Sciences Publications, 2017.","ama":"Renault T, Abraham A, Bergmiller T, et al. Bacterial flagella grow through an injection diffusion mechanism. eLife. 2017;6. doi:10.7554/eLife.23136","apa":"Renault, T., Abraham, A., Bergmiller, T., Paradis, G., Rainville, S., Charpentier, E., … Erhardt, M. (2017). Bacterial flagella grow through an injection diffusion mechanism. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.23136","ista":"Renault T, Abraham A, Bergmiller T, Paradis G, Rainville S, Charpentier E, Guet CC, Tu Y, Namba K, Keener J, Minamino T, Erhardt M. 2017. Bacterial flagella grow through an injection diffusion mechanism. eLife. 6, e23136.","short":"T. Renault, A. Abraham, T. Bergmiller, G. Paradis, S. Rainville, E. Charpentier, C.C. Guet, Y. Tu, K. Namba, J. Keener, T. Minamino, M. Erhardt, ELife 6 (2017).","mla":"Renault, Thibaud, et al. “Bacterial Flagella Grow through an Injection Diffusion Mechanism.” ELife, vol. 6, e23136, eLife Sciences Publications, 2017, doi:10.7554/eLife.23136."},"year":"2017","doi":"10.7554/eLife.23136","day":"06","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."}],"quality_controlled":"1","file_date_updated":"2020-07-14T12:47:33Z","publisher":"eLife Sciences Publications","_id":"655","scopus_import":1,"author":[{"first_name":"Thibaud","last_name":"Renault","full_name":"Renault, Thibaud"},{"first_name":"Anthony","last_name":"Abraham","full_name":"Abraham, Anthony"},{"first_name":"Tobias","last_name":"Bergmiller","orcid":"0000-0001-5396-4346","full_name":"Bergmiller, Tobias","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Paradis, Guillaume","first_name":"Guillaume","last_name":"Paradis"},{"first_name":"Simon","last_name":"Rainville","full_name":"Rainville, Simon"},{"last_name":"Charpentier","first_name":"Emmanuelle","full_name":"Charpentier, Emmanuelle"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","last_name":"Guet","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C"},{"last_name":"Tu","first_name":"Yuhai","full_name":"Tu, Yuhai"},{"full_name":"Namba, Keiichi","last_name":"Namba","first_name":"Keiichi"},{"last_name":"Keener","first_name":"James","full_name":"Keener, James"},{"full_name":"Minamino, Tohru","first_name":"Tohru","last_name":"Minamino"},{"first_name":"Marc","last_name":"Erhardt","full_name":"Erhardt, Marc"}],"publication_status":"published","date_created":"2018-12-11T11:47:44Z","department":[{"_id":"CaGu"}],"title":"Bacterial flagella grow through an injection diffusion mechanism","pubrep_id":"904","intvolume":" 6"},{"file":[{"relation":"main_file","access_level":"open_access","creator":"system","file_id":"4805","checksum":"7873f665a0c598ac747c908f34cb14b9","file_size":710206,"date_created":"2018-12-12T10:10:19Z","file_name":"IST-2016-658-v1+1_s00453-016-0212-1.pdf","content_type":"application/pdf","date_updated":"2020-07-14T12:44:44Z"}],"status":"public","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","publication_identifier":{"issn":["01784617"]},"oa":1,"publist_id":"5931","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"date_published":"2017-06-01T00:00:00Z","type":"journal_article","language":[{"iso":"eng"}],"oa_version":"Published Version","project":[{"_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"618091","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation"}],"month":"06","publication":"Algorithmica","has_accepted_license":"1","volume":78,"ddc":["576"],"doi":"10.1007/s00453-016-0212-1","day":"01","abstract":[{"lang":"eng","text":"Evolutionary algorithms (EAs) form a popular optimisation paradigm inspired by natural evolution. In recent years the field of evolutionary computation has developed a rigorous analytical theory to analyse the runtimes of EAs on many illustrative problems. Here we apply this theory to a simple model of natural evolution. In the Strong Selection Weak Mutation (SSWM) evolutionary regime the time between occurrences of new mutations is much longer than the time it takes for a mutated genotype to take over the population. In this situation, the population only contains copies of one genotype and evolution can be modelled as a stochastic process evolving one genotype by means of mutation and selection between the resident and the mutated genotype. The probability of accepting the mutated genotype then depends on the change in fitness. We study this process, SSWM, from an algorithmic perspective, quantifying its expected optimisation time for various parameters and investigating differences to a similar evolutionary algorithm, the well-known (1+1) EA. We show that SSWM can have a moderate advantage over the (1+1) EA at crossing fitness valleys and study an example where SSWM outperforms the (1+1) EA by taking advantage of information on the fitness gradient."}],"date_updated":"2023-09-20T11:14:42Z","year":"2017","citation":{"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.","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","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.","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."},"isi":1,"external_id":{"isi":["000400379500013"]},"publisher":"Springer","page":"681 - 713","quality_controlled":"1","ec_funded":1,"file_date_updated":"2020-07-14T12:44:44Z","publication_status":"published","date_created":"2018-12-11T11:51:27Z","article_processing_charge":"No","department":[{"_id":"NiBa"},{"_id":"CaGu"}],"title":"Towards a runtime comparison of natural and artificial evolution","pubrep_id":"658","intvolume":" 78","_id":"1336","scopus_import":"1","author":[{"orcid":"0000-0003-2361-3953","full_name":"Paixao, Tiago","first_name":"Tiago","last_name":"Paixao","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Pérez Heredia, Jorge","first_name":"Jorge","last_name":"Pérez Heredia"},{"full_name":"Sudholt, Dirk","first_name":"Dirk","last_name":"Sudholt"},{"first_name":"Barbora","last_name":"Trubenova","orcid":"0000-0002-6873-2967","full_name":"Trubenova, Barbora","id":"42302D54-F248-11E8-B48F-1D18A9856A87"}],"issue":"2"},{"month":"12","oa_version":"Published Version","project":[{"grant_number":"267989","name":"Quantitative Reactive Modeling","call_identifier":"FP7","_id":"25EE3708-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","_id":"25832EC2-B435-11E9-9278-68D0E5697425","name":"Rigorous Systems Engineering","grant_number":"S 11407_N23"},{"call_identifier":"FWF","_id":"25F42A32-B435-11E9-9278-68D0E5697425","grant_number":"Z211","name":"The Wittgenstein Prize"},{"grant_number":"618091","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"},{"name":"International IST Postdoc Fellowship Programme","grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"},{"grant_number":"250152","name":"Limits to selection in biology and in evolutionary computation","_id":"25B07788-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"}],"publication":"Acta Informatica","has_accepted_license":"1","language":[{"iso":"eng"}],"publist_id":"5898","oa":1,"publication_identifier":{"issn":["00015903"]},"date_published":"2017-12-01T00:00:00Z","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","related_material":{"record":[{"status":"public","id":"1835","relation":"earlier_version"}]},"status":"public","file":[{"access_level":"open_access","relation":"main_file","creator":"dernst","file_id":"5841","checksum":"4e661d9135d7f8c342e8e258dee76f3e","file_size":755241,"date_created":"2019-01-17T15:57:29Z","file_name":"2017_ActaInformatica_Giacobbe.pdf","content_type":"application/pdf","date_updated":"2020-07-14T12:44:46Z"}],"title":"Model checking the evolution of gene regulatory networks","pubrep_id":"649","intvolume":" 54","publication_status":"published","date_created":"2018-12-11T11:51:32Z","department":[{"_id":"ToHe"},{"_id":"CaGu"},{"_id":"NiBa"}],"article_processing_charge":"No","author":[{"orcid":"0000-0001-8180-0904","full_name":"Giacobbe, Mirco","first_name":"Mirco","last_name":"Giacobbe","id":"3444EA5E-F248-11E8-B48F-1D18A9856A87"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052"},{"id":"335E5684-F248-11E8-B48F-1D18A9856A87","first_name":"Ashutosh","last_name":"Gupta","full_name":"Gupta, Ashutosh"},{"id":"40876CD8-F248-11E8-B48F-1D18A9856A87","first_name":"Thomas A","last_name":"Henzinger","orcid":"0000−0002−2985−7724","full_name":"Henzinger, Thomas A"},{"id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2361-3953","full_name":"Paixao, Tiago","first_name":"Tiago","last_name":"Paixao"},{"id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9041-0905","full_name":"Petrov, Tatjana","first_name":"Tatjana","last_name":"Petrov"}],"issue":"8","_id":"1351","scopus_import":"1","publisher":"Springer","file_date_updated":"2020-07-14T12:44:46Z","page":"765 - 787","ec_funded":1,"quality_controlled":"1","abstract":[{"text":"The behaviour of gene regulatory networks (GRNs) is typically analysed using simulation-based statistical testing-like methods. In this paper, we demonstrate that we can replace this approach by a formal verification-like method that gives higher assurance and scalability. We focus on Wagner’s weighted GRN model with varying weights, which is used in evolutionary biology. In the model, weight parameters represent the gene interaction strength that may change due to genetic mutations. For a property of interest, we synthesise the constraints over the parameter space that represent the set of GRNs satisfying the property. We experimentally show that our parameter synthesis procedure computes the mutational robustness of GRNs—an important problem of interest in evolutionary biology—more efficiently than the classical simulation method. We specify the property in linear temporal logic. We employ symbolic bounded model checking and SMT solving to compute the space of GRNs that satisfy the property, which amounts to synthesizing a set of linear constraints on the weights.","lang":"eng"}],"doi":"10.1007/s00236-016-0278-x","day":"01","isi":1,"external_id":{"isi":["000414343200003"]},"date_updated":"2025-05-28T11:57:04Z","year":"2017","citation":{"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.","ista":"Giacobbe M, Guet CC, Gupta A, Henzinger TA, Paixao T, Petrov T. 2017. Model checking the evolution of gene regulatory networks. Acta Informatica. 54(8), 765–787.","apa":"Giacobbe, M., Guet, C. C., Gupta, A., Henzinger, T. A., Paixao, T., & Petrov, T. (2017). Model checking the evolution of gene regulatory networks. Acta Informatica. Springer. https://doi.org/10.1007/s00236-016-0278-x","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.","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."},"ddc":["006","576"],"volume":54},{"_id":"954","scopus_import":"1","author":[{"id":"345D25EC-F248-11E8-B48F-1D18A9856A87","first_name":"Mato","last_name":"Lagator","full_name":"Lagator, Mato"},{"orcid":"0000-0003-2361-3953","full_name":"Paixao, Tiago","first_name":"Tiago","last_name":"Paixao","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Barton, Nicholas H","orcid":"0000-0002-8548-5240","last_name":"Barton","first_name":"Nicholas H","id":"4880FE40-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Bollback","first_name":"Jonathan P","full_name":"Bollback, Jonathan P","orcid":"0000-0002-4624-4612","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","first_name":"Calin C","last_name":"Guet"}],"publication_status":"published","date_created":"2018-12-11T11:49:23Z","article_processing_charge":"Yes","department":[{"_id":"CaGu"},{"_id":"NiBa"},{"_id":"JoBo"}],"title":"On the mechanistic nature of epistasis in a canonical cis-regulatory element","pubrep_id":"841","intvolume":" 6","ec_funded":1,"quality_controlled":"1","file_date_updated":"2020-07-14T12:48:16Z","publisher":"eLife Sciences Publications","date_updated":"2023-09-22T10:01:17Z","year":"2017","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.","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).","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.","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.","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","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"},"isi":1,"external_id":{"isi":["000404024800001"]},"doi":"10.7554/eLife.25192","day":"18","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"}],"volume":6,"ddc":["576"],"publication":"eLife","has_accepted_license":"1","oa_version":"Published Version","project":[{"name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","grant_number":"618091","call_identifier":"FP7","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425"},{"grant_number":"291734","name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425"},{"_id":"2578D616-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"648440","name":"Selective Barriers to Horizontal Gene Transfer"}],"month":"05","article_number":"e25192","language":[{"iso":"eng"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"date_published":"2017-05-18T00:00:00Z","type":"journal_article","publication_identifier":{"issn":["2050084X"]},"oa":1,"publist_id":"6460","file":[{"access_level":"open_access","relation":"main_file","creator":"system","file_id":"5306","checksum":"59cdd4400fb41280122d414fea971546","file_size":2441529,"date_created":"2018-12-12T10:17:49Z","content_type":"application/pdf","file_name":"IST-2017-841-v1+1_elife-25192-v2.pdf","date_updated":"2020-07-14T12:48:16Z"},{"file_id":"5307","creator":"system","access_level":"open_access","relation":"main_file","date_updated":"2020-07-14T12:48:16Z","content_type":"application/pdf","file_name":"IST-2017-841-v1+2_elife-25192-figures-v2.pdf","date_created":"2018-12-12T10:17:50Z","file_size":3752660,"checksum":"b69024880558b858eb8c5d47a92b6377"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","status":"public"},{"publication":"Automatica","has_accepted_license":"1","month":"06","oa_version":"Published Version","project":[{"_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme","grant_number":"291734"}],"language":[{"iso":"eng"}],"date_published":"2017-06-01T00:00:00Z","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"oa":1,"publist_id":"6391","publication_identifier":{"issn":["0005-1098"]},"status":"public","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file":[{"relation":"main_file","access_level":"open_access","creator":"system","file_id":"4884","file_size":1401954,"date_created":"2018-12-12T10:11:29Z","file_name":"IST-2017-813-v1+1_ZerosOfNonlinearSystems.pdf","content_type":"application/pdf","date_updated":"2018-12-12T10:11:29Z"}],"author":[{"id":"29E0800A-F248-11E8-B48F-1D18A9856A87","last_name":"Lang","first_name":"Moritz","full_name":"Lang, Moritz"},{"last_name":"Sontag","first_name":"Eduardo","full_name":"Sontag, Eduardo"}],"_id":"1007","scopus_import":"1","title":"Zeros of nonlinear systems with input invariances","pubrep_id":"813","publication_status":"published","article_processing_charge":"Yes (in subscription journal)","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"date_created":"2018-12-11T11:49:39Z","file_date_updated":"2018-12-12T10:11:29Z","page":"46 - 55","quality_controlled":"1","ec_funded":1,"publisher":"International Federation of Automatic Control","isi":1,"external_id":{"isi":["000403513900006"]},"date_updated":"2023-10-17T08:51:18Z","year":"2017","citation":{"ista":"Lang M, Sontag E. 2017. Zeros of nonlinear systems with input invariances. Automatica. 81C, 46–55.","short":"M. Lang, E. Sontag, Automatica 81C (2017) 46–55.","mla":"Lang, Moritz, and Eduardo Sontag. “Zeros of Nonlinear Systems with Input Invariances.” Automatica, vol. 81C, International Federation of Automatic Control, 2017, pp. 46–55, doi:10.1016/j.automatica.2017.03.030.","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.","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.","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"},"abstract":[{"lang":"eng","text":"A nonlinear system possesses an invariance with respect to a set of transformations if its output dynamics remain invariant when transforming the input, and adjusting the initial condition accordingly. Most research has focused on invariances with respect to time-independent pointwise transformations like translational-invariance (u(t) -> 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."}],"doi":"10.1016/j.automatica.2017.03.030","day":"01","ddc":["000"],"volume":"81C"},{"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"date_published":"2017-03-20T00:00:00Z","type":"journal_article","publication_identifier":{"issn":["14337851"]},"publist_id":"6362","oa":1,"file":[{"date_created":"2019-01-18T09:39:55Z","file_size":2614942,"date_updated":"2019-01-18T09:39:55Z","content_type":"application/pdf","file_name":"2017_communications_Kainrath.pdf","success":1,"relation":"main_file","access_level":"open_access","file_id":"5845","creator":"dernst"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","status":"public","related_material":{"record":[{"relation":"dissertation_contains","id":"418","status":"public"},{"status":"public","id":"7680","relation":"part_of_dissertation"}]},"publication":"Angewandte Chemie - International Edition","has_accepted_license":"1","oa_version":"Published Version","project":[{"grant_number":"303564","name":"Microbial Ion Channels for Synthetic Neurobiology","_id":"25548C20-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"},{"_id":"26AA4EF2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"W1232-B24","name":"Molecular Drug Targets [do not use to be deleted]"}],"month":"03","language":[{"iso":"eng"}],"date_updated":"2024-03-25T23:30:08Z","citation":{"mla":"Kainrath, Stephanie, et al. “Green-Light-Induced Inactivation of Receptor Signaling Using Cobalamin-Binding Domains.” Angewandte Chemie - International Edition, vol. 56, no. 16, Wiley-Blackwell, 2017, pp. 4608–11, doi:10.1002/anie.201611998.","short":"S. Kainrath, M. Stadler, E. Gschaider-Reichhart, M. Distel, H.L. Janovjak, Angewandte Chemie - International Edition 56 (2017) 4608–4611.","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.","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","apa":"Kainrath, S., Stadler, M., Gschaider-Reichhart, E., Distel, M., & Janovjak, H. L. (2017). Green-light-induced inactivation of receptor signaling using cobalamin-binding domains. Angewandte Chemie - International Edition. Wiley-Blackwell. https://doi.org/10.1002/anie.201611998","ieee":"S. Kainrath, M. Stadler, E. Gschaider-Reichhart, M. Distel, and H. L. Janovjak, “Green-light-induced inactivation of receptor signaling using cobalamin-binding domains,” Angewandte Chemie - International Edition, vol. 56, no. 16. Wiley-Blackwell, pp. 4608–4611, 2017.","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."},"year":"2017","isi":1,"external_id":{"isi":["000398154000038"]},"doi":"10.1002/anie.201611998","day":"20","abstract":[{"text":"Optogenetics and photopharmacology provide spatiotemporally precise control over protein interactions and protein function in cells and animals. Optogenetic methods that are sensitive to green light and can be used to break protein complexes are not broadly available but would enable multichromatic experiments with previously inaccessible biological targets. Herein, we repurposed cobalamin (vitamin B12) binding domains of bacterial CarH transcription factors for green-light-induced receptor dissociation. In cultured cells, we observed oligomerization-induced cell signaling for the fibroblast growth factor receptor 1 fused to cobalamin-binding domains in the dark that was rapidly eliminated upon illumination. In zebrafish embryos expressing fusion receptors, green light endowed control over aberrant fibroblast growth factor signaling during development. Green-light-induced domain dissociation and light-inactivated receptors will critically expand the optogenetic toolbox for control of biological processes.","lang":"eng"}],"acknowledgement":"This work was supported by a grant from the European Unions Seventh Framework Programme (CIG-303564). 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Mobility Fellowship – grant number P300P2_161067.","volume":59,"ddc":["004"],"doi":"10.4230/LIPIcs.CONCUR.2016.20","day":"01","abstract":[{"text":"We introduce a general class of distances (metrics) between Markov chains, which are based on linear behaviour. This class encompasses distances given topologically (such as the total variation distance or trace distance) as well as by temporal logics or automata. We investigate which of the distances can be approximated by observing the systems, i.e. by black-box testing or simulation, and we provide both negative and positive results. ","lang":"eng"}],"date_updated":"2023-09-07T11:58:33Z","year":"2016","citation":{"ista":"Daca P, Henzinger TA, Kretinsky J, Petrov T. 2016. Linear distances between Markov chains. CONCUR: Concurrency Theory, LIPIcs, vol. 59, 20.","mla":"Daca, Przemyslaw, et al. Linear Distances between Markov Chains. Vol. 59, 20, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2016, doi:10.4230/LIPIcs.CONCUR.2016.20.","short":"P. Daca, T.A. Henzinger, J. Kretinsky, T. Petrov, in:, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2016.","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.","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","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"}},{"language":[{"iso":"eng"}],"month":"11","oa_version":"Submitted Version","has_accepted_license":"1","publication":"SIAM Journal on Scientific Computing","status":"public","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","file":[{"content_type":"application/pdf","file_name":"IST-2017-811-v1+1_modular_parameter_identification.pdf","date_updated":"2020-07-14T12:44:37Z","checksum":"781bc3ffd30b2dd65b7727c5a285fc78","file_size":871964,"date_created":"2018-12-12T10:14:41Z","creator":"system","file_id":"5095","relation":"main_file","access_level":"local"}],"publist_id":"6186","type":"journal_article","date_published":"2016-11-15T00:00:00Z","publisher":"Society for Industrial and Applied Mathematics ","file_date_updated":"2020-07-14T12:44:37Z","quality_controlled":"1","page":"B988 - B1008","intvolume":" 38","title":"Modular parameter identification of biomolecular networks","pubrep_id":"811","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"date_created":"2018-12-11T11:50:31Z","publication_status":"published","issue":"6","author":[{"id":"29E0800A-F248-11E8-B48F-1D18A9856A87","full_name":"Lang, Moritz","first_name":"Moritz","last_name":"Lang"},{"full_name":"Stelling, Jörg","last_name":"Stelling","first_name":"Jörg"}],"scopus_import":1,"_id":"1170","ddc":["003","518","570","621"],"volume":38,"abstract":[{"lang":"eng","text":"The increasing complexity of dynamic models in systems and synthetic biology poses computational challenges especially for the identification of model parameters. While modularization of the corresponding optimization problems could help reduce the “curse of dimensionality,” abundant feedback and crosstalk mechanisms prohibit a simple decomposition of most biomolecular networks into subnetworks, or modules. Drawing on ideas from network modularization and multiple-shooting optimization, we present here a modular parameter identification approach that explicitly allows for such interdependencies. Interfaces between our modules are given by the experimentally measured molecular species. This definition allows deriving good (initial) estimates for the inter-module communication directly from the experimental data. Given these estimates, the states and parameter sensitivities of different modules can be integrated independently. To achieve consistency between modules, we iteratively adjust the estimates for inter-module communication while optimizing the parameters. After convergence to an optimal parameter set---but not during earlier iterations---the intermodule communication as well as the individual modules\\' state dynamics agree with the dynamics of the nonmodularized network. Our modular parameter identification approach allows for easy parallelization; it can reduce the computational complexity for larger networks and decrease the probability to converge to suboptimal local minima. We demonstrate the algorithm\\'s performance in parameter estimation for two biomolecular networks, a synthetic genetic oscillator and a mammalian signaling pathway."}],"day":"15","doi":"10.1137/15M103306X","year":"2016","citation":{"ista":"Lang M, Stelling J. 2016. Modular parameter identification of biomolecular networks. SIAM Journal on Scientific Computing. 38(6), B988–B1008.","short":"M. Lang, J. Stelling, SIAM Journal on Scientific Computing 38 (2016) B988–B1008.","mla":"Lang, Moritz, and Jörg Stelling. “Modular Parameter Identification of Biomolecular Networks.” SIAM Journal on Scientific Computing, vol. 38, no. 6, Society for Industrial and Applied Mathematics , 2016, pp. B988–1008, doi:10.1137/15M103306X.","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.","ieee":"M. Lang and J. Stelling, “Modular parameter identification of biomolecular networks,” SIAM Journal on Scientific Computing, vol. 38, no. 6. Society for Industrial and Applied Mathematics , pp. B988–B1008, 2016.","apa":"Lang, M., & Stelling, J. (2016). Modular parameter identification of biomolecular networks. SIAM Journal on Scientific Computing. Society for Industrial and Applied Mathematics . https://doi.org/10.1137/15M103306X","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"},"date_updated":"2021-01-12T06:48:49Z"},{"language":[{"iso":"eng"}],"has_accepted_license":"1","publication":"Molecular Biology and Evolution","oa_version":"Published Version","month":"03","file":[{"creator":"dernst","file_id":"5750","relation":"main_file","access_level":"open_access","file_name":"2016_MolBiolEvol_Wielgoss.pdf","content_type":"application/pdf","date_updated":"2020-07-14T12:47:10Z","checksum":"47d9010690b6c5c17f2ac830cc63ac5c","file_size":634037,"date_created":"2018-12-18T13:21:45Z"}],"related_material":{"record":[{"id":"9719","relation":"research_data","status":"public"}]},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","status":"public","tmp":{"name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","image":"/images/cc_by_nc.png","short":"CC BY-NC (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode"},"type":"journal_article","date_published":"2016-03-01T00:00:00Z","publication_identifier":{"issn":["0737-4038"],"eissn":["1537-1719"]},"oa":1,"quality_controlled":"1","page":"770-782","file_date_updated":"2020-07-14T12:47:10Z","publisher":"Oxford University Press","scopus_import":"1","pmid":1,"_id":"5749","issue":"3","author":[{"full_name":"Wielgoss, Sébastien","last_name":"Wielgoss","first_name":"Sébastien"},{"id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","full_name":"Bergmiller, Tobias","orcid":"0000-0001-5396-4346","last_name":"Bergmiller","first_name":"Tobias"},{"full_name":"Bischofberger, Anna M.","last_name":"Bischofberger","first_name":"Anna M."},{"first_name":"Alex R.","last_name":"Hall","full_name":"Hall, Alex R."}],"department":[{"_id":"CaGu"}],"article_processing_charge":"No","date_created":"2018-12-18T13:18:10Z","publication_status":"published","intvolume":" 33","title":"Adaptation to parasites and costs of parasite resistance in mutator and nonmutator bacteria","pubrep_id":"587","volume":33,"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.).","ddc":["576"],"year":"2016","citation":{"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.","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","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","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.","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."},"date_updated":"2023-09-05T13:46:05Z","external_id":{"pmid":["26609077"]},"day":"01","doi":"10.1093/molbev/msv270","abstract":[{"text":"Parasitism creates selection for resistance mechanisms in host populations and is hypothesized to promote increased host evolvability. However, the influence of these traits on host evolution when parasites are no longer present is unclear. We used experimental evolution and whole-genome sequencing of Escherichia coli to determine the effects of past and present exposure to parasitic viruses (phages) on the spread of mutator alleles, resistance, and bacterial competitive fitness. We found that mutator alleles spread rapidly during adaptation to any of four different phage species, and this pattern was even more pronounced with multiple phages present simultaneously. However, hypermutability did not detectably accelerate adaptation in the absence of phages and recovery of fitness costs associated with resistance. Several lineages evolved phage resistance through elevated mucoidy, and during subsequent evolution in phage-free conditions they rapidly reverted to nonmucoid, phage-susceptible phenotypes. Genome sequencing revealed that this phenotypic reversion was achieved by additional genetic changes rather than by genotypic reversion of the initial resistance mutations. Insertion sequence (IS) elements played a key role in both the acquisition of resistance and adaptation in the absence of parasites; unlike single nucleotide polymorphisms, IS insertions were not more frequent in mutator lineages. Our results provide a genetic explanation for rapid reversion of mucoidy, a phenotype observed in other bacterial species including human pathogens. Moreover, this demonstrates that the types of genetic change underlying adaptation to fitness costs, and consequently the impact of evolvability mechanisms such as increased point-mutation rates, depend critically on the mechanism of resistance.","lang":"eng"}]}]