[{"pubrep_id":"1014","date_published":"2018-05-01T00:00:00Z","file":[{"checksum":"7d92f5d7be81e387edeec4f06442791c","date_updated":"2020-07-14T12:47:54Z","relation":"main_file","date_created":"2018-12-12T10:08:14Z","creator":"system","content_type":"application/pdf","file_size":691245,"access_level":"open_access","file_id":"4674","file_name":"IST-2018-1014-v1+1_2018_Paixao_Escape.pdf"}],"author":[{"first_name":"Pietro","last_name":"Oliveto","full_name":"Oliveto, Pietro"},{"orcid":"0000-0003-2361-3953","last_name":"Paixao","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","first_name":"Tiago","full_name":"Paixao, Tiago"},{"full_name":"Pérez Heredia, Jorge","last_name":"Pérez Heredia","first_name":"Jorge"},{"full_name":"Sudholt, Dirk","last_name":"Sudholt","first_name":"Dirk"},{"full_name":"Trubenova, Barbora","id":"42302D54-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6873-2967","last_name":"Trubenova","first_name":"Barbora"}],"publication_status":"published","page":"1604 - 1633","title":"How to escape local optima in black box optimisation when non elitism outperforms elitism","isi":1,"file_date_updated":"2020-07-14T12:47:54Z","doi":"10.1007/s00453-017-0369-2","publist_id":"6957","language":[{"iso":"eng"}],"ec_funded":1,"oa_version":"Published Version","status":"public","department":[{"_id":"NiBa"},{"_id":"CaGu"}],"citation":{"apa":"Oliveto, P., Paixao, T., Pérez Heredia, J., Sudholt, D., &#38; Trubenova, B. (2018). How to escape local optima in black box optimisation when non elitism outperforms elitism. <i>Algorithmica</i>. Springer. <a href=\"https://doi.org/10.1007/s00453-017-0369-2\">https://doi.org/10.1007/s00453-017-0369-2</a>","chicago":"Oliveto, Pietro, Tiago Paixao, Jorge Pérez Heredia, Dirk Sudholt, and Barbora Trubenova. “How to Escape Local Optima in Black Box Optimisation When Non Elitism Outperforms Elitism.” <i>Algorithmica</i>. Springer, 2018. <a href=\"https://doi.org/10.1007/s00453-017-0369-2\">https://doi.org/10.1007/s00453-017-0369-2</a>.","short":"P. Oliveto, T. Paixao, J. Pérez Heredia, D. Sudholt, B. Trubenova, Algorithmica 80 (2018) 1604–1633.","ama":"Oliveto P, Paixao T, Pérez Heredia J, Sudholt D, Trubenova B. How to escape local optima in black box optimisation when non elitism outperforms elitism. <i>Algorithmica</i>. 2018;80(5):1604-1633. doi:<a href=\"https://doi.org/10.1007/s00453-017-0369-2\">10.1007/s00453-017-0369-2</a>","ista":"Oliveto P, Paixao T, Pérez Heredia J, Sudholt D, Trubenova B. 2018. How to escape local optima in black box optimisation when non elitism outperforms elitism. Algorithmica. 80(5), 1604–1633.","mla":"Oliveto, Pietro, et al. “How to Escape Local Optima in Black Box Optimisation When Non Elitism Outperforms Elitism.” <i>Algorithmica</i>, vol. 80, no. 5, Springer, 2018, pp. 1604–33, doi:<a href=\"https://doi.org/10.1007/s00453-017-0369-2\">10.1007/s00453-017-0369-2</a>.","ieee":"P. Oliveto, T. Paixao, J. Pérez Heredia, D. Sudholt, and B. Trubenova, “How to escape local optima in black box optimisation when non elitism outperforms elitism,” <i>Algorithmica</i>, vol. 80, no. 5. Springer, pp. 1604–1633, 2018."},"quality_controlled":"1","date_updated":"2025-04-15T08:22:22Z","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","image":"/images/cc_by.png","short":"CC BY (4.0)"},"_id":"723","intvolume":"        80","date_created":"2018-12-11T11:48:09Z","project":[{"grant_number":"618091","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"}],"fulldoi":"https://doi.org/10.1007/s00453-017-0369-2","year":"2018","issue":"5","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","type":"journal_article","month":"05","publication":"Algorithmica","external_id":{"isi":["000428239300010"]},"oa":1,"article_processing_charge":"No","publisher":"Springer","has_accepted_license":"1","ddc":["576"],"day":"01","volume":80,"abstract":[{"text":"Escaping local optima is one of the major obstacles to function optimisation. Using the metaphor of a fitness landscape, local optima correspond to hills separated by fitness valleys that have to be overcome. We define a class of fitness valleys of tunable difficulty by considering their length, representing the Hamming path between the two optima and their depth, the drop in fitness. For this function class we present a runtime comparison between stochastic search algorithms using different search strategies. The (1+1) EA is a simple and well-studied evolutionary algorithm that has to jump across the valley to a point of higher fitness because it does not accept worsening moves (elitism). In contrast, the Metropolis algorithm and the Strong Selection Weak Mutation (SSWM) algorithm, a famous process in population genetics, are both able to cross the fitness valley by accepting worsening moves. We show that the runtime of the (1+1) EA depends critically on the length of the valley while the runtimes of the non-elitist algorithms depend crucially on the depth of the valley. Moreover, we show that both SSWM and Metropolis can also efficiently optimise a rugged function consisting of consecutive valleys.","lang":"eng"}],"scopus_import":"1"},{"pubrep_id":"1059","doi":"10.15479/AT:ISTA:th1059","file_date_updated":"2021-02-11T11:17:14Z","title":"The influence of sequence context on the evolution of bacterial gene expression","page":"109","file":[{"access_level":"closed","file_id":"5941","file_name":"Thesis_Steinrueck_final.docx","relation":"source_file","checksum":"413cbce1cd1debeae3abe2a25dbc70d1","date_updated":"2020-07-14T12:45:43Z","embargo_to":"open_access","creator":"dernst","date_created":"2019-02-08T10:51:22Z","file_size":9190845,"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document"},{"file_name":"Thesis_Steinrueck_final.pdf","file_id":"5942","access_level":"open_access","file_size":7521973,"content_type":"application/pdf","embargo":"2019-11-02","creator":"dernst","date_created":"2019-02-08T10:51:22Z","relation":"main_file","date_updated":"2021-02-11T11:17:14Z","checksum":"3def8b7854c8b42d643597ce0215efac"}],"date_published":"2018-10-30T00:00:00Z","author":[{"orcid":"0000-0003-1229-9719","last_name":"Steinrück","id":"2C023F40-F248-11E8-B48F-1D18A9856A87","first_name":"Magdalena","full_name":"Steinrück, Magdalena"}],"publication_status":"published","citation":{"ieee":"M. Steinrück, “The influence of sequence context on the evolution of bacterial gene expression,” Institute of Science and Technology Austria, 2018.","mla":"Steinrück, Magdalena. <i>The Influence of Sequence Context on the Evolution of Bacterial Gene Expression</i>. Institute of Science and Technology Austria, 2018, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:th1059\">10.15479/AT:ISTA:th1059</a>.","ista":"Steinrück M. 2018. The influence of sequence context on the evolution of bacterial gene expression. Institute of Science and Technology Austria.","ama":"Steinrück M. The influence of sequence context on the evolution of bacterial gene expression. 2018. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:th1059\">10.15479/AT:ISTA:th1059</a>","short":"M. Steinrück, The Influence of Sequence Context on the Evolution of Bacterial Gene Expression, Institute of Science and Technology Austria, 2018.","chicago":"Steinrück, Magdalena. “The Influence of Sequence Context on the Evolution of Bacterial Gene Expression.” Institute of Science and Technology Austria, 2018. <a href=\"https://doi.org/10.15479/AT:ISTA:th1059\">https://doi.org/10.15479/AT:ISTA:th1059</a>.","apa":"Steinrück, M. (2018). <i>The influence of sequence context on the evolution of bacterial gene expression</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:th1059\">https://doi.org/10.15479/AT:ISTA:th1059</a>"},"department":[{"_id":"CaGu"}],"status":"public","degree_awarded":"PhD","oa_version":"Published Version","language":[{"iso":"eng"}],"publist_id":"8029","date_created":"2018-12-11T11:44:14Z","_id":"26","date_updated":"2026-04-08T14:15:35Z","alternative_title":["ISTA Thesis"],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","year":"2018","supervisor":[{"orcid":"0000-0001-6220-2052","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","full_name":"Guet, Calin C"}],"fulldoi":"https://doi.org/10.15479/AT:ISTA:th1059","type":"dissertation","article_processing_charge":"No","oa":1,"OA_place":"publisher","month":"10","related_material":{"record":[{"id":"704","status":"public","relation":"part_of_dissertation"}]},"abstract":[{"text":"Expression of genes is a fundamental molecular phenotype that is subject to evolution by different types of mutations. Both the rate and the effect of mutations may depend on the DNA sequence context of a particular gene or a particular promoter sequence. In this thesis I investigate the nature of this dependence using simple genetic systems in Escherichia coli. With these systems I explore the evolution of constitutive gene expression from random starting sequences at different loci on the chromosome and at different locations in sequence space. First, I dissect chromosomal neighborhood effects that underlie locus-dependent differences in the potential of a gene under selection to become more highly expressed. Next, I find that the effects of point mutations in promoter sequences are dependent on sequence context, and that an existing energy matrix model performs poorly in predicting relative expression of unrelated sequences. Finally, I show that a substantial fraction of random sequences contain functional promoters and I present an extended thermodynamic model that predicts promoter strength in full sequence space. Taken together, these results provide new insights and guides on how to integrate information on sequence context to improve our qualitative and quantitative understanding of bacterial gene expression, with implications for rapid evolution of drug resistance, de novo evolution of genes, and horizontal gene transfer.","lang":"eng"}],"publication_identifier":{"issn":["2663-337X"]},"day":"30","has_accepted_license":"1","ddc":["576","579"],"publisher":"Institute of Science and Technology Austria","corr_author":"1"},{"intvolume":"         2","date_created":"2018-12-11T11:44:27Z","quality_controlled":"1","_id":"67","date_updated":"2026-11-02T23:30:29Z","ec_funded":1,"oa_version":"Submitted Version","publist_id":"7987","language":[{"iso":"eng"}],"department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"JoBo"}],"citation":{"short":"C. Igler, M. Lagator, G. Tkačik, J.P. Bollback, C.C. Guet, Nature Ecology and Evolution 2 (2018) 1633–1643.","chicago":"Igler, Claudia, Mato Lagator, Gašper Tkačik, Jonathan P Bollback, and Calin C Guet. “Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring.” <i>Nature Ecology and Evolution</i>. Nature Publishing Group, 2018. <a href=\"https://doi.org/10.1038/s41559-018-0651-y\">https://doi.org/10.1038/s41559-018-0651-y</a>.","apa":"Igler, C., Lagator, M., Tkačik, G., Bollback, J. P., &#38; Guet, C. C. (2018). Evolutionary potential of transcription factors for gene regulatory rewiring. <i>Nature Ecology and Evolution</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/s41559-018-0651-y\">https://doi.org/10.1038/s41559-018-0651-y</a>","ieee":"C. Igler, M. Lagator, G. Tkačik, J. P. Bollback, and C. C. Guet, “Evolutionary potential of transcription factors for gene regulatory rewiring,” <i>Nature Ecology and Evolution</i>, vol. 2, no. 10. Nature Publishing Group, pp. 1633–1643, 2018.","mla":"Igler, Claudia, et al. “Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring.” <i>Nature Ecology and Evolution</i>, vol. 2, no. 10, Nature Publishing Group, 2018, pp. 1633–43, doi:<a href=\"https://doi.org/10.1038/s41559-018-0651-y\">10.1038/s41559-018-0651-y</a>.","ista":"Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. 2018. Evolutionary potential of transcription factors for gene regulatory rewiring. Nature Ecology and Evolution. 2(10), 1633–1643.","ama":"Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. Evolutionary potential of transcription factors for gene regulatory rewiring. <i>Nature Ecology and Evolution</i>. 2018;2(10):1633-1643. doi:<a href=\"https://doi.org/10.1038/s41559-018-0651-y\">10.1038/s41559-018-0651-y</a>"},"status":"public","date_published":"2018-09-10T00:00:00Z","publication_status":"published","file":[{"file_size":1135973,"content_type":"application/pdf","date_created":"2020-05-14T11:28:52Z","creator":"dernst","checksum":"383a2e2c944a856e2e821ec8e7bf71b6","date_updated":"2020-07-14T12:47:37Z","relation":"main_file","file_name":"2018_NatureEcology_Igler.pdf","file_id":"7830","access_level":"open_access"}],"author":[{"full_name":"Igler, Claudia","last_name":"Igler","orcid":"0000-0001-7777-546X","id":"46613666-F248-11E8-B48F-1D18A9856A87","first_name":"Claudia"},{"last_name":"Lagator","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","first_name":"Mato","full_name":"Lagator, Mato"},{"full_name":"Tkacik, Gasper","first_name":"Gasper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","last_name":"Tkacik","orcid":"0000-0002-6699-1455"},{"first_name":"Jonathan P","orcid":"0000-0002-4624-4612","last_name":"Bollback","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","full_name":"Bollback, Jonathan P"},{"full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","last_name":"Guet","first_name":"Calin C"}],"page":"1633 - 1643","isi":1,"file_date_updated":"2020-07-14T12:47:37Z","title":"Evolutionary potential of transcription factors for gene regulatory rewiring","doi":"10.1038/s41559-018-0651-y","ddc":["570"],"has_accepted_license":"1","publisher":"Nature Publishing Group","abstract":[{"text":"Gene regulatory networks evolve through rewiring of individual components—that is, through changes in regulatory connections. However, the mechanistic basis of regulatory rewiring is poorly understood. Using a canonical gene regulatory system, we quantify the properties of transcription factors that determine the evolutionary potential for rewiring of regulatory connections: robustness, tunability and evolvability. In vivo repression measurements of two repressors at mutated operator sites reveal their contrasting evolutionary potential: while robustness and evolvability were positively correlated, both were in trade-off with tunability. Epistatic interactions between adjacent operators alleviated this trade-off. A thermodynamic model explains how the differences in robustness, tunability and evolvability arise from biophysical characteristics of repressor–DNA binding. The model also uncovers that the energy matrix, which describes how mutations affect repressor–DNA binding, encodes crucial information about the evolutionary potential of a repressor. The biophysical determinants of evolutionary potential for regulatory rewiring constitute a mechanistic framework for understanding network evolution.","lang":"eng"}],"scopus_import":"1","day":"10","volume":2,"related_material":{"record":[{"id":"5585","status":"public","relation":"popular_science"},{"status":"public","relation":"dissertation_contains","id":"6371"}]},"month":"09","oa":1,"article_processing_charge":"No","publication":"Nature Ecology and Evolution","external_id":{"isi":["000447947600021"]},"article_type":"original","type":"journal_article","fulldoi":"https://doi.org/10.1038/s41559-018-0651-y","project":[{"name":"International IST Postdoc Fellowship Programme","_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"291734"},{"name":"Selective Barriers to Horizontal Gene Transfer","call_identifier":"H2020","_id":"2578D616-B435-11E9-9278-68D0E5697425","grant_number":"648440"},{"name":"Design principles underlying genetic switch architecture","_id":"251EE76E-B435-11E9-9278-68D0E5697425","grant_number":"24573"}],"year":"2018","issue":"10","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1"},{"date_created":"2018-12-12T12:31:40Z","date_updated":"2026-11-02T23:30:29Z","tmp":{"short":"CC0 (1.0)","name":"Creative Commons Public Domain Dedication (CC0 1.0)","legal_code_url":"https://creativecommons.org/publicdomain/zero/1.0/legalcode","image":"/images/cc_0.png"},"_id":"5585","ec_funded":1,"oa_version":"Published Version","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"citation":{"chicago":"Igler, Claudia, Mato Lagator, Gašper Tkačik, Jonathan P Bollback, and Calin C Guet. “Data for the Paper Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring.” Institute of Science and Technology Austria, 2018. <a href=\"https://doi.org/10.15479/AT:ISTA:108\">https://doi.org/10.15479/AT:ISTA:108</a>.","apa":"Igler, C., Lagator, M., Tkačik, G., Bollback, J. P., &#38; Guet, C. C. (2018). Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:108\">https://doi.org/10.15479/AT:ISTA:108</a>","short":"C. Igler, M. Lagator, G. Tkačik, J.P. Bollback, C.C. Guet, (2018).","ista":"Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. 2018. Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:108\">10.15479/AT:ISTA:108</a>.","ama":"Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring. 2018. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:108\">10.15479/AT:ISTA:108</a>","mla":"Igler, Claudia, et al. <i>Data for the Paper Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring</i>. Institute of Science and Technology Austria, 2018, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:108\">10.15479/AT:ISTA:108</a>.","ieee":"C. Igler, M. Lagator, G. Tkačik, J. P. Bollback, and C. C. Guet, “Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring.” Institute of Science and Technology Austria, 2018."},"status":"public","author":[{"first_name":"Claudia","id":"46613666-F248-11E8-B48F-1D18A9856A87","last_name":"Igler","orcid":"0000-0001-7777-546X","full_name":"Igler, Claudia"},{"first_name":"Mato","last_name":"Lagator","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","full_name":"Lagator, Mato"},{"first_name":"Gasper","orcid":"0000-0002-6699-1455","last_name":"Tkacik","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkacik, Gasper"},{"first_name":"Jonathan P","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","last_name":"Bollback","orcid":"0000-0002-4624-4612","full_name":"Bollback, Jonathan P"},{"full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","orcid":"0000-0001-6220-2052","first_name":"Calin C"}],"date_published":"2018-07-20T00:00:00Z","file":[{"relation":"main_file","date_updated":"2020-07-14T12:47:07Z","checksum":"1435781526c77413802adee0d4583cce","creator":"system","date_created":"2018-12-12T13:02:45Z","content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","file_size":16507,"access_level":"open_access","file_id":"5611","file_name":"IST-2018-108-v1+1_data_figures.xlsx"}],"file_date_updated":"2020-07-14T12:47:07Z","title":"Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring","datarep_id":"108","doi":"10.15479/AT:ISTA:108","has_accepted_license":"1","ddc":["576"],"publisher":"Institute of Science and Technology Austria","abstract":[{"lang":"eng","text":"Mean repression values and standard error of the mean are given for all operator mutant libraries."}],"day":"20","related_material":{"record":[{"status":"public","relation":"research_paper","id":"67"},{"relation":"research_paper","status":"public","id":"6371"}]},"month":"07","oa":1,"article_processing_charge":"No","type":"research_data","fulldoi":"https://doi.org/10.15479/AT:ISTA:108","project":[{"name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734"},{"call_identifier":"H2020","_id":"2578D616-B435-11E9-9278-68D0E5697425","name":"Selective Barriers to Horizontal Gene Transfer","grant_number":"648440"},{"_id":"251EE76E-B435-11E9-9278-68D0E5697425","name":"Design principles underlying genetic switch architecture","grant_number":"24573"}],"year":"2018","license":"https://creativecommons.org/publicdomain/zero/1.0/","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"},{"date_created":"2018-12-11T11:50:03Z","intvolume":"       104","_id":"1084","date_updated":"2026-04-16T09:56:09Z","quality_controlled":"1","oa_version":"None","language":[{"iso":"eng"}],"publist_id":"6294","citation":{"apa":"Fang, C., Nagy-Staron, A. A., Grafe, M., Heermann, R., Jung, K., Gebhard, S., &#38; Mascher, T. (2017). Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis. <i>Molecular Microbiology</i>. Wiley-Blackwell. <a href=\"https://doi.org/10.1111/mmi.13597\">https://doi.org/10.1111/mmi.13597</a>","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.” <i>Molecular Microbiology</i>. Wiley-Blackwell, 2017. <a href=\"https://doi.org/10.1111/mmi.13597\">https://doi.org/10.1111/mmi.13597</a>.","short":"C. Fang, A.A. Nagy-Staron, M. Grafe, R. Heermann, K. Jung, S. Gebhard, T. Mascher, Molecular Microbiology 104 (2017) 16–31.","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. <i>Molecular Microbiology</i>. 2017;104(1):16-31. doi:<a href=\"https://doi.org/10.1111/mmi.13597\">10.1111/mmi.13597</a>","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.","mla":"Fang, Chong, et al. “Insulation and Wiring Specificity of BceR like Response Regulators and Their Target Promoters in Bacillus Subtilis.” <i>Molecular Microbiology</i>, vol. 104, no. 1, Wiley-Blackwell, 2017, pp. 16–31, doi:<a href=\"https://doi.org/10.1111/mmi.13597\">10.1111/mmi.13597</a>.","ieee":"C. Fang <i>et al.</i>, “Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis,” <i>Molecular Microbiology</i>, vol. 104, no. 1. Wiley-Blackwell, pp. 16–31, 2017."},"department":[{"_id":"CaGu"}],"status":"public","page":"16 - 31","date_published":"2017-04-01T00:00:00Z","author":[{"first_name":"Chong","last_name":"Fang","full_name":"Fang, Chong"},{"full_name":"Nagy-Staron, Anna A","first_name":"Anna A","orcid":"0000-0002-1391-8377","last_name":"Nagy-Staron","id":"3ABC5BA6-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Grafe","first_name":"Martin","full_name":"Grafe, Martin"},{"first_name":"Ralf","last_name":"Heermann","full_name":"Heermann, Ralf"},{"full_name":"Jung, Kirsten","last_name":"Jung","first_name":"Kirsten"},{"first_name":"Susanne","last_name":"Gebhard","full_name":"Gebhard, Susanne"},{"first_name":"Thorsten","last_name":"Mascher","full_name":"Mascher, Thorsten"}],"publication_status":"published","doi":"10.1111/mmi.13597","isi":1,"title":"Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis","publisher":"Wiley-Blackwell","scopus_import":"1","abstract":[{"text":"BceRS and PsdRS are paralogous two-component systems in Bacillus subtilis controlling the response to antimicrobial peptides. In the presence of extracellular bacitracin and nisin, respectively, the two response regulators (RRs) bind their target promoters, PbceA or PpsdA, resulting in a strong up-regulation of target gene expression and ultimately antibiotic resistance. Despite high sequence similarity between the RRs BceR and PsdR and their known binding sites, no cross-regulation has been observed between them. We therefore investigated the specificity determinants of PbceA and PpsdA that ensure the insulation of these two paralogous pathways at the RR–promoter interface. In vivo and in vitro analyses demonstrate that the regulatory regions within these two promoters contain three important elements: in addition to the known (main) binding site, we identified a linker region and a secondary binding site that are crucial for functionality. Initial binding to the high-affinity, low-specificity main binding site is a prerequisite for the subsequent highly specific binding of a second RR dimer to the low-affinity secondary binding site. In addition to this hierarchical cooperative binding, discrimination requires a competition of the two RRs for their respective binding site mediated by only slight differences in binding affinities.","lang":"eng"}],"publication_identifier":{"issn":[" 0950-382X"]},"volume":104,"day":"01","month":"04","article_processing_charge":"No","external_id":{"isi":["000398059200002"]},"publication":"Molecular Microbiology","type":"journal_article","year":"2017","fulldoi":"https://doi.org/10.1111/mmi.13597","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","issue":"1"},{"language":[{"iso":"eng"}],"publist_id":"5931","oa_version":"Published Version","ec_funded":1,"status":"public","citation":{"apa":"Paixao, T., Pérez Heredia, J., Sudholt, D., &#38; Trubenova, B. (2017). Towards a runtime comparison of natural and artificial evolution. <i>Algorithmica</i>. Springer. <a href=\"https://doi.org/10.1007/s00453-016-0212-1\">https://doi.org/10.1007/s00453-016-0212-1</a>","chicago":"Paixao, Tiago, Jorge Pérez Heredia, Dirk Sudholt, and Barbora Trubenova. “Towards a Runtime Comparison of Natural and Artificial Evolution.” <i>Algorithmica</i>. Springer, 2017. <a href=\"https://doi.org/10.1007/s00453-016-0212-1\">https://doi.org/10.1007/s00453-016-0212-1</a>.","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.” <i>Algorithmica</i>, vol. 78, no. 2, Springer, 2017, pp. 681–713, doi:<a href=\"https://doi.org/10.1007/s00453-016-0212-1\">10.1007/s00453-016-0212-1</a>.","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.","ama":"Paixao T, Pérez Heredia J, Sudholt D, Trubenova B. Towards a runtime comparison of natural and artificial evolution. <i>Algorithmica</i>. 2017;78(2):681-713. doi:<a href=\"https://doi.org/10.1007/s00453-016-0212-1\">10.1007/s00453-016-0212-1</a>","ieee":"T. Paixao, J. Pérez Heredia, D. Sudholt, and B. Trubenova, “Towards a runtime comparison of natural and artificial evolution,” <i>Algorithmica</i>, vol. 78, no. 2. Springer, pp. 681–713, 2017."},"department":[{"_id":"NiBa"},{"_id":"CaGu"}],"_id":"1336","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","image":"/images/cc_by.png","short":"CC BY (4.0)"},"date_updated":"2026-04-16T09:55:33Z","quality_controlled":"1","date_created":"2018-12-11T11:51:27Z","intvolume":"        78","pubrep_id":"658","page":"681 - 713","publication_status":"published","author":[{"orcid":"0000-0003-2361-3953","last_name":"Paixao","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","first_name":"Tiago","full_name":"Paixao, Tiago"},{"first_name":"Jorge","last_name":"Pérez Heredia","full_name":"Pérez Heredia, Jorge"},{"full_name":"Sudholt, Dirk","last_name":"Sudholt","first_name":"Dirk"},{"full_name":"Trubenova, Barbora","id":"42302D54-F248-11E8-B48F-1D18A9856A87","last_name":"Trubenova","orcid":"0000-0002-6873-2967","first_name":"Barbora"}],"date_published":"2017-06-01T00:00:00Z","file":[{"content_type":"application/pdf","file_size":710206,"date_created":"2018-12-12T10:10:19Z","creator":"system","date_updated":"2020-07-14T12:44:44Z","checksum":"7873f665a0c598ac747c908f34cb14b9","relation":"main_file","file_name":"IST-2016-658-v1+1_s00453-016-0212-1.pdf","file_id":"4805","access_level":"open_access"}],"doi":"10.1007/s00453-016-0212-1","file_date_updated":"2020-07-14T12:44:44Z","isi":1,"title":"Towards a runtime comparison of natural and artificial evolution","month":"06","publication":"Algorithmica","external_id":{"isi":["000400379500013"]},"article_processing_charge":"No","oa":1,"publisher":"Springer","ddc":["576"],"has_accepted_license":"1","volume":78,"day":"01","scopus_import":"1","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"}],"publication_identifier":{"issn":["0178-4617"]},"year":"2017","fulldoi":"https://doi.org/10.1007/s00453-016-0212-1","project":[{"name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","call_identifier":"FP7","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","grant_number":"618091"}],"issue":"2","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","type":"journal_article"},{"volume":54,"day":"01","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"}],"scopus_import":"1","publication_identifier":{"issn":["0001-5903"]},"publisher":"Springer","corr_author":"1","has_accepted_license":"1","ddc":["006","576"],"external_id":{"isi":["000414343200003"]},"publication":"Acta Informatica","article_processing_charge":"No","oa":1,"month":"12","related_material":{"record":[{"id":"1835","relation":"earlier_version","status":"public"}]},"type":"journal_article","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","issue":"8","year":"2017","fulldoi":"https://doi.org/10.1007/s00236-016-0278-x","project":[{"name":"Quantitative Reactive Modeling","call_identifier":"FP7","_id":"25EE3708-B435-11E9-9278-68D0E5697425","grant_number":"267989"},{"name":"Rigorous Systems Engineering","call_identifier":"FWF","_id":"25832EC2-B435-11E9-9278-68D0E5697425","grant_number":"S 11407_N23"},{"grant_number":"Z211","name":"Formal methods for the design and analysis of complex systems","call_identifier":"FWF","_id":"25F42A32-B435-11E9-9278-68D0E5697425"},{"name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"618091"},{"grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme"},{"grant_number":"250152","call_identifier":"FP7","_id":"25B07788-B435-11E9-9278-68D0E5697425","name":"Limits to selection in biology and in evolutionary computation"}],"date_updated":"2025-07-10T11:50:42Z","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","image":"/images/cc_by.png","short":"CC BY (4.0)"},"_id":"1351","quality_controlled":"1","date_created":"2018-12-11T11:51:32Z","intvolume":"        54","status":"public","citation":{"apa":"Giacobbe, M., Guet, C. C., Gupta, A., Henzinger, T. A., Paixao, T., &#38; Petrov, T. (2017). Model checking the evolution of gene regulatory networks. <i>Acta Informatica</i>. Springer. <a href=\"https://doi.org/10.1007/s00236-016-0278-x\">https://doi.org/10.1007/s00236-016-0278-x</a>","chicago":"Giacobbe, Mirco, Calin C Guet, Ashutosh Gupta, Thomas A Henzinger, Tiago Paixao, and Tatjana Petrov. “Model Checking the Evolution of Gene Regulatory Networks.” <i>Acta Informatica</i>. Springer, 2017. <a href=\"https://doi.org/10.1007/s00236-016-0278-x\">https://doi.org/10.1007/s00236-016-0278-x</a>.","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.” <i>Acta Informatica</i>, vol. 54, no. 8, Springer, 2017, pp. 765–87, doi:<a href=\"https://doi.org/10.1007/s00236-016-0278-x\">10.1007/s00236-016-0278-x</a>.","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. <i>Acta Informatica</i>. 2017;54(8):765-787. doi:<a href=\"https://doi.org/10.1007/s00236-016-0278-x\">10.1007/s00236-016-0278-x</a>","ieee":"M. Giacobbe, C. C. Guet, A. Gupta, T. A. Henzinger, T. Paixao, and T. Petrov, “Model checking the evolution of gene regulatory networks,” <i>Acta Informatica</i>, vol. 54, no. 8. Springer, pp. 765–787, 2017."},"department":[{"_id":"ToHe"},{"_id":"CaGu"},{"_id":"NiBa"}],"language":[{"iso":"eng"}],"publist_id":"5898","oa_version":"Published Version","ec_funded":1,"doi":"10.1007/s00236-016-0278-x","title":"Model checking the evolution of gene regulatory networks","file_date_updated":"2020-07-14T12:44:46Z","isi":1,"page":"765 - 787","file":[{"access_level":"open_access","file_id":"5841","file_name":"2017_ActaInformatica_Giacobbe.pdf","relation":"main_file","checksum":"4e661d9135d7f8c342e8e258dee76f3e","date_updated":"2020-07-14T12:44:46Z","creator":"dernst","date_created":"2019-01-17T15:57:29Z","content_type":"application/pdf","file_size":755241}],"date_published":"2017-12-01T00:00:00Z","author":[{"first_name":"Mirco","orcid":"0000-0001-8180-0904","last_name":"Giacobbe","id":"3444EA5E-F248-11E8-B48F-1D18A9856A87","full_name":"Giacobbe, Mirco"},{"first_name":"Calin C","orcid":"0000-0001-6220-2052","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C"},{"full_name":"Gupta, Ashutosh","first_name":"Ashutosh","last_name":"Gupta","id":"335E5684-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Henzinger","orcid":"0000−0002−2985−7724","id":"40876CD8-F248-11E8-B48F-1D18A9856A87","first_name":"Thomas A","full_name":"Henzinger, Thomas A"},{"first_name":"Tiago","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2361-3953","last_name":"Paixao","full_name":"Paixao, Tiago"},{"full_name":"Petrov, Tatjana","first_name":"Tatjana","id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9041-0905","last_name":"Petrov"}],"publication_status":"published","pubrep_id":"649"},{"page":"4679 - 4682","file":[{"content_type":"application/pdf","file_size":1668557,"relation":"main_file","checksum":"d66fee867e7cdbfa3fe276c2fb0778bb","date_updated":"2020-07-14T12:46:39Z","creator":"system","date_created":"2018-12-12T10:13:24Z","file_name":"IST-2018-932-v1+1_Kainrath_et_al-2017-Angewandte_Chemie.pdf","access_level":"open_access","file_id":"5007"}],"publication_status":"published","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"},{"first_name":"Eva","orcid":"0000-0002-7218-7738","last_name":"Gschaider-Reichhart","id":"3FEE232A-F248-11E8-B48F-1D18A9856A87","full_name":"Gschaider-Reichhart, Eva"},{"full_name":"Distel, Martin","last_name":"Distel","first_name":"Martin"},{"first_name":"Harald L","last_name":"Janovjak","orcid":"0000-0002-8023-9315","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","full_name":"Janovjak, Harald L"}],"date_published":"2017-05-20T00:00:00Z","doi":"10.1002/ange.201611998","file_date_updated":"2020-07-14T12:46:39Z","title":"Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen","pubrep_id":"932","date_created":"2018-12-11T11:47:02Z","intvolume":"       129","_id":"538","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","image":"/images/cc_by.png","short":"CC BY (4.0)"},"date_updated":"2024-10-09T20:58:07Z","quality_controlled":"1","oa_version":"Published Version","ec_funded":1,"language":[{"iso":"eng"}],"publist_id":"7279","citation":{"chicago":"Kainrath, Stephanie, Manuela Stadler, Eva Gschaider-Reichhart, Martin Distel, and Harald L Janovjak. “Grünlicht-Induzierte Rezeptorinaktivierung Durch Cobalamin-Bindende Domänen.” <i>Angewandte Chemie</i>. Wiley, 2017. <a href=\"https://doi.org/10.1002/ange.201611998\">https://doi.org/10.1002/ange.201611998</a>.","apa":"Kainrath, S., Stadler, M., Gschaider-Reichhart, E., Distel, M., &#38; Janovjak, H. L. (2017). Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen. <i>Angewandte Chemie</i>. Wiley. <a href=\"https://doi.org/10.1002/ange.201611998\">https://doi.org/10.1002/ange.201611998</a>","short":"S. Kainrath, M. Stadler, E. Gschaider-Reichhart, M. Distel, H.L. Janovjak, Angewandte Chemie 129 (2017) 4679–4682.","ista":"Kainrath S, Stadler M, Gschaider-Reichhart E, Distel M, Janovjak HL. 2017. Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen. Angewandte Chemie. 129(16), 4679–4682.","ama":"Kainrath S, Stadler M, Gschaider-Reichhart E, Distel M, Janovjak HL. Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen. <i>Angewandte Chemie</i>. 2017;129(16):4679-4682. doi:<a href=\"https://doi.org/10.1002/ange.201611998\">10.1002/ange.201611998</a>","mla":"Kainrath, Stephanie, et al. “Grünlicht-Induzierte Rezeptorinaktivierung Durch Cobalamin-Bindende Domänen.” <i>Angewandte Chemie</i>, vol. 129, no. 16, Wiley, 2017, pp. 4679–82, doi:<a href=\"https://doi.org/10.1002/ange.201611998\">10.1002/ange.201611998</a>.","ieee":"S. Kainrath, M. Stadler, E. Gschaider-Reichhart, M. Distel, and H. L. Janovjak, “Grünlicht-induzierte Rezeptorinaktivierung durch Cobalamin-bindende Domänen,” <i>Angewandte Chemie</i>, vol. 129, no. 16. Wiley, pp. 4679–4682, 2017."},"department":[{"_id":"CaGu"},{"_id":"HaJa"}],"status":"public","type":"journal_article","year":"2017","project":[{"grant_number":"303564","_id":"25548C20-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"Microbial Ion Channels for Synthetic Neurobiology"},{"grant_number":"W1232-B24","name":"Molecular Drug Targets","_id":"255A6082-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"fulldoi":"https://doi.org/10.1002/ange.201611998","issue":"16","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","has_accepted_license":"1","ddc":["571"],"corr_author":"1","publisher":"Wiley","abstract":[{"lang":"ger","text":"Optogenetik und Photopharmakologie ermöglichen präzise räumliche und zeitliche Kontrolle von Proteinwechselwirkung und -funktion in Zellen und Tieren. Optogenetische Methoden, die auf grünes Licht ansprechen und zum Trennen von Proteinkomplexen geeignet sind, sind nichtweitläufig verfügbar, würden jedoch mehrfarbige Experimente zur Beantwortung von biologischen Fragestellungen ermöglichen. Hier demonstrieren wir die Verwendung von Cobalamin(Vitamin B12)-bindenden Domänen von bakteriellen CarH-Transkriptionsfaktoren zur Grünlicht-induzierten Dissoziation von Rezeptoren. Fusioniert mit dem Fibroblasten-W achstumsfaktor-Rezeptor 1 führten diese im Dunkeln in kultivierten Zellen zu Signalaktivität durch Oligomerisierung, welche durch Beleuchten umgehend aufgehoben wurde. In Zebrafischembryonen, die einen derartigen Rezeptor exprimieren, ermöglichte grünes Licht die Kontrolle über abnormale Signalaktivität während der Embryonalentwicklung. "}],"volume":129,"day":"20","month":"05","oa":1,"publication":"Angewandte Chemie"},{"oa":1,"article_processing_charge":"No","publication":"PLoS Genetics","external_id":{"isi":["000419103000015"]},"related_material":{"record":[{"status":"public","relation":"research_data","id":"9844"},{"status":"public","relation":"research_data","id":"9845"},{"id":"9846","relation":"research_data","status":"public"}]},"month":"12","publication_identifier":{"issn":["1553-7390"]},"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."}],"scopus_import":"1","day":"18","volume":13,"has_accepted_license":"1","ddc":["576","579"],"publisher":"Public Library of Science","corr_author":"1","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","issue":"12","project":[{"name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734"}],"fulldoi":"https://doi.org/10.1371/journal.pgen.1007122","year":"2017","type":"journal_article","department":[{"_id":"CaGu"}],"citation":{"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. <i>PLoS Genetics</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pgen.1007122\">https://doi.org/10.1371/journal.pgen.1007122</a>","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.” <i>PLoS Genetics</i>. Public Library of Science, 2017. <a href=\"https://doi.org/10.1371/journal.pgen.1007122\">https://doi.org/10.1371/journal.pgen.1007122</a>.","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.” <i>PLoS Genetics</i>, vol. 13, no. 12, e1007122, Public Library of Science, 2017, doi:<a href=\"https://doi.org/10.1371/journal.pgen.1007122\">10.1371/journal.pgen.1007122</a>.","ama":"Nikolic N, Schreiber F, Dal Co A, et al. Cell-to-cell variation and specialization in sugar metabolism in clonal bacterial populations. <i>PLoS Genetics</i>. 2017;13(12). doi:<a href=\"https://doi.org/10.1371/journal.pgen.1007122\">10.1371/journal.pgen.1007122</a>","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.","ieee":"N. Nikolic <i>et al.</i>, “Cell-to-cell variation and specialization in sugar metabolism in clonal bacterial populations,” <i>PLoS Genetics</i>, vol. 13, no. 12. Public Library of Science, 2017."},"status":"public","ec_funded":1,"oa_version":"Published Version","publist_id":"7275","language":[{"iso":"eng"}],"intvolume":"        13","date_created":"2018-12-11T11:47:04Z","article_number":"e1007122","quality_controlled":"1","date_updated":"2025-09-18T09:42:09Z","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","image":"/images/cc_by.png","short":"CC BY (4.0)"},"_id":"541","pubrep_id":"959","title":"Cell-to-cell variation and specialization in sugar metabolism in clonal bacterial populations","file_date_updated":"2020-07-14T12:46:46Z","isi":1,"doi":"10.1371/journal.pgen.1007122","publication_status":"published","date_published":"2017-12-18T00:00:00Z","file":[{"file_id":"5088","access_level":"open_access","file_name":"IST-2018-959-v1+1_2017_Nikolic_Cell-to-cell.pdf","date_created":"2018-12-12T10:14:35Z","creator":"system","checksum":"22426d9382f21554bad5fa5967afcfd0","date_updated":"2020-07-14T12:46:46Z","relation":"main_file","content_type":"application/pdf","file_size":1308475}],"author":[{"full_name":"Nikolic, Nela","id":"42D9CABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9068-6090","last_name":"Nikolic","first_name":"Nela"},{"first_name":"Frank","last_name":"Schreiber","full_name":"Schreiber, Frank"},{"full_name":"Dal Co, Alma","first_name":"Alma","last_name":"Dal Co"},{"full_name":"Kiviet, Daniel","last_name":"Kiviet","first_name":"Daniel"},{"first_name":"Tobias","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","last_name":"Bergmiller","orcid":"0000-0001-5396-4346","full_name":"Bergmiller, Tobias"},{"full_name":"Littmann, Sten","last_name":"Littmann","first_name":"Sten"},{"first_name":"Marcel","last_name":"Kuypers","full_name":"Kuypers, Marcel"},{"last_name":"Ackermann","first_name":"Martin","full_name":"Ackermann, Martin"}]},{"year":"2017","fulldoi":"https://doi.org/10.15479/AT:ISTA:53","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_published":"2017-03-10T00:00:00Z","author":[{"full_name":"Bergmiller, Tobias","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5396-4346","last_name":"Bergmiller","first_name":"Tobias"},{"full_name":"Andersson, Anna M","first_name":"Anna M","id":"2B8A40DA-F248-11E8-B48F-1D18A9856A87","last_name":"Andersson","orcid":"0000-0003-2912-6769"},{"full_name":"Tomasek, Kathrin","orcid":"0000-0003-3768-877X","last_name":"Tomasek","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","first_name":"Kathrin"},{"first_name":"Enrique","last_name":"Balleza","full_name":"Balleza, Enrique"},{"last_name":"Kiviet","first_name":"Daniel","full_name":"Kiviet, Daniel"},{"full_name":"Hauschild, Robert","first_name":"Robert","orcid":"0000-0001-9843-3522","last_name":"Hauschild","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Tkacik","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gasper","full_name":"Tkacik, Gasper"},{"full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","orcid":"0000-0001-6220-2052","first_name":"Calin C"}],"file":[{"file_id":"5603","access_level":"open_access","file_name":"IST-2017-53-v1+1_Data_MDE.zip","date_created":"2018-12-12T13:02:38Z","creator":"system","date_updated":"2020-07-14T12:47:03Z","checksum":"d77859af757ac8025c50c7b12b52eaf3","relation":"main_file","file_size":6773204,"content_type":"application/zip"}],"keyword":["single cell microscopy","mother machine microfluidic device","AcrAB-TolC pump","multi-drug efflux","Escherichia coli"],"datarep_id":"53","doi":"10.15479/AT:ISTA:53","title":"Biased partitioning of the multi-drug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity","file_date_updated":"2020-07-14T12:47:03Z","type":"research_data","oa_version":"Published Version","month":"03","related_material":{"record":[{"id":"665","status":"public","relation":"research_paper"}]},"article_processing_charge":"No","citation":{"short":"T. Bergmiller, A.M. Andersson, K. Tomasek, E. Balleza, D. Kiviet, R. Hauschild, G. Tkačik, C.C. Guet, (2017).","chicago":"Bergmiller, Tobias, Anna M Andersson, Kathrin Tomasek, Enrique Balleza, Daniel Kiviet, Robert Hauschild, Gašper Tkačik, and Calin C Guet. “Biased Partitioning of the Multi-Drug Efflux Pump AcrAB-TolC Underlies Long-Lived Phenotypic Heterogeneity.” Institute of Science and Technology Austria, 2017. <a href=\"https://doi.org/10.15479/AT:ISTA:53\">https://doi.org/10.15479/AT:ISTA:53</a>.","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. <a href=\"https://doi.org/10.15479/AT:ISTA:53\">https://doi.org/10.15479/AT:ISTA:53</a>","ieee":"T. Bergmiller <i>et al.</i>, “Biased partitioning of the multi-drug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity.” Institute of Science and Technology Austria, 2017.","mla":"Bergmiller, Tobias, et al. <i>Biased Partitioning of the Multi-Drug Efflux Pump AcrAB-TolC Underlies Long-Lived Phenotypic Heterogeneity</i>. Institute of Science and Technology Austria, 2017, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:53\">10.15479/AT:ISTA:53</a>.","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:<a href=\"https://doi.org/10.15479/AT:ISTA:53\">10.15479/AT:ISTA:53</a>","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, <a href=\"https://doi.org/10.15479/AT:ISTA:53\">10.15479/AT:ISTA:53</a>."},"department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"Bio"}],"oa":1,"status":"public","has_accepted_license":"1","ddc":["571"],"publisher":"Institute of Science and Technology Austria","abstract":[{"lang":"eng","text":"This repository contains the data collected for the manuscript \"Biased partitioning of the multi-drug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity\".\r\nThe data is compressed into a single archive. Within the archive, different folders correspond to figures of the main text and the SI of the related publication.\r\nData is saved as plain text, with each folder containing a separate readme file describing the format. Typically, the data is from fluorescence microscopy measurements of single cells growing in a microfluidic \"mother machine\" device, and consists of relevant values (primarily arbitrary unit or normalized fluorescence measurements, and division times / growth rates) after raw microscopy images have been processed, segmented, and their features extracted, as described in the methods section of the related publication."}],"date_created":"2018-12-12T12:31:32Z","tmp":{"short":"CC0 (1.0)","name":"Creative Commons Public Domain Dedication (CC0 1.0)","legal_code_url":"https://creativecommons.org/publicdomain/zero/1.0/legalcode","image":"/images/cc_0.png"},"_id":"5560","date_updated":"2025-09-11T07:05:03Z","day":"10"},{"datarep_id":"65","doi":"10.15479/AT:ISTA:65","file_date_updated":"2020-07-14T12:47:03Z","title":"Fastq files for \"Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection\"","type":"research_data","file":[{"file_name":"IST-2017-65-v1+1_D_anc_1.fastq.zip","access_level":"open_access","file_id":"5627","file_size":1225959109,"content_type":"application/zip","relation":"main_file","date_updated":"2020-07-14T12:47:03Z","checksum":"31a0c01d022721073241a23d192cc37e","creator":"system","date_created":"2018-12-12T13:03:18Z"},{"file_size":1422656107,"content_type":"application/zip","creator":"system","date_created":"2018-12-12T13:03:30Z","relation":"main_file","checksum":"d8f26f83ce7e7e45436121f9c6cd9b83","date_updated":"2020-07-14T12:47:03Z","file_name":"IST-2017-65-v1+1_D_anc_2.fastq.zip","file_id":"5628","access_level":"open_access"},{"file_name":"IST-2017-65-v1+2_D_A11_1.fastq.zip","access_level":"open_access","file_id":"5629","file_size":565014975,"content_type":"application/zip","date_updated":"2020-07-14T12:47:03Z","checksum":"e07b99bcfe55b5f132ca03b8b48c8cbc","relation":"main_file","date_created":"2018-12-12T13:03:33Z","creator":"system"},{"file_name":"IST-2017-65-v1+3_D_A11_2.fastq.zip","file_id":"5630","access_level":"open_access","content_type":"application/zip","file_size":564490030,"date_created":"2018-12-12T13:03:42Z","creator":"system","date_updated":"2020-07-14T12:47:03Z","checksum":"eda86143d5f32d844b54f8530041e32b","relation":"main_file"},{"file_size":875430169,"content_type":"application/zip","relation":"main_file","date_updated":"2020-07-14T12:47:03Z","checksum":"906d44f950c1626d9b99f34fbf89cb12","creator":"system","date_created":"2018-12-12T13:03:46Z","file_name":"IST-2017-65-v1+4_D_C10_1.fastq.zip","access_level":"open_access","file_id":"5631"},{"access_level":"open_access","file_id":"5632","file_name":"IST-2017-65-v1+6_D_C08_2.fastq.zip","date_updated":"2020-07-14T12:47:03Z","checksum":"6ca14a032a79e0c787106bdf635725c9","relation":"main_file","date_created":"2018-12-12T13:03:54Z","creator":"system","content_type":"application/zip","file_size":638298201},{"content_type":"application/zip","file_size":894702866,"creator":"system","date_created":"2018-12-12T13:04:01Z","relation":"main_file","checksum":"66ab16ddb5ba64b2e263ef746ebf2893","date_updated":"2020-07-14T12:47:03Z","file_name":"IST-2017-65-v1+5_D_C10_2.fastq.zip","file_id":"5633","access_level":"open_access"},{"file_name":"IST-2017-65-v1+7_D_C08_1.fastq.zip","file_id":"5634","access_level":"open_access","file_size":623648989,"content_type":"application/zip","date_created":"2018-12-12T13:04:07Z","creator":"system","date_updated":"2020-07-14T12:47:03Z","checksum":"82607970174f8d37773b7d3acc712195","relation":"main_file"},{"relation":"main_file","checksum":"225c30b243268c7dda9d6f8327933252","date_updated":"2020-07-14T12:47:03Z","creator":"system","date_created":"2018-12-12T13:04:11Z","file_size":259359583,"content_type":"application/zip","access_level":"open_access","file_id":"5635","file_name":"IST-2017-65-v1+8_D_D08_1.fastq.zip"}],"author":[{"id":"2C023F40-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1229-9719","last_name":"Steinrück","first_name":"Magdalena","full_name":"Steinrück, Magdalena"},{"first_name":"Calin C","last_name":"Guet","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C"}],"date_published":"2017-04-11T00:00:00Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","year":"2017","fulldoi":"https://doi.org/10.15479/AT:ISTA:65","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"}],"date_created":"2018-12-12T12:31:33Z","tmp":{"short":"CC0 (1.0)","name":"Creative Commons Public Domain Dedication (CC0 1.0)","legal_code_url":"https://creativecommons.org/publicdomain/zero/1.0/legalcode","image":"/images/cc_0.png"},"date_updated":"2025-09-10T11:06:52Z","_id":"5564","day":"11","has_accepted_license":"1","ddc":["576"],"publisher":"Institute of Science and Technology Austria","citation":{"ama":"Steinrück M, Guet CC. Fastq files for “Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection.” 2017. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:65\">10.15479/AT:ISTA:65</a>","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, <a href=\"https://doi.org/10.15479/AT:ISTA:65\">10.15479/AT:ISTA:65</a>.","mla":"Steinrück, Magdalena, and Calin C. Guet. <i>Fastq Files for “Complex Chromosomal Neighborhood Effects Determine the Adaptive Potential of a Gene under Selection.”</i> Institute of Science and Technology Austria, 2017, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:65\">10.15479/AT:ISTA:65</a>.","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., &#38; 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. <a href=\"https://doi.org/10.15479/AT:ISTA:65\">https://doi.org/10.15479/AT:ISTA:65</a>","chicago":"Steinrück, Magdalena, and Calin C Guet. “Fastq Files for ‘Complex Chromosomal Neighborhood Effects Determine the Adaptive Potential of a Gene under Selection.’” Institute of Science and Technology Austria, 2017. <a href=\"https://doi.org/10.15479/AT:ISTA:65\">https://doi.org/10.15479/AT:ISTA:65</a>.","short":"M. Steinrück, C.C. Guet, (2017)."},"article_processing_charge":"No","oa":1,"department":[{"_id":"CaGu"}],"status":"public","oa_version":"Published Version","month":"04","related_material":{"record":[{"id":"704","relation":"research_paper","status":"public"}]}},{"date_created":"2018-12-11T11:47:11Z","intvolume":"        13","_id":"561","date_updated":"2026-06-18T18:54:20Z","quality_controlled":"1","article_number":"20170646","citation":{"ieee":"M. Pleska and C. C. Guet, “Effects of mutations in phage restriction sites during escape from restriction–modification,” <i>Biology Letters</i>, vol. 13, no. 12. The Royal Society, 2017.","mla":"Pleska, Maros, and Calin C. Guet. “Effects of Mutations in Phage Restriction Sites during Escape from Restriction–Modification.” <i>Biology Letters</i>, vol. 13, no. 12, 20170646, The Royal Society, 2017, doi:<a href=\"https://doi.org/10.1098/rsbl.2017.0646\">10.1098/rsbl.2017.0646</a>.","ama":"Pleska M, Guet CC. Effects of mutations in phage restriction sites during escape from restriction–modification. <i>Biology Letters</i>. 2017;13(12). doi:<a href=\"https://doi.org/10.1098/rsbl.2017.0646\">10.1098/rsbl.2017.0646</a>","ista":"Pleska M, Guet CC. 2017. Effects of mutations in phage restriction sites during escape from restriction–modification. Biology Letters. 13(12), 20170646.","short":"M. Pleska, C.C. Guet, Biology Letters 13 (2017).","apa":"Pleska, M., &#38; Guet, C. C. (2017). Effects of mutations in phage restriction sites during escape from restriction–modification. <i>Biology Letters</i>. The Royal Society. <a href=\"https://doi.org/10.1098/rsbl.2017.0646\">https://doi.org/10.1098/rsbl.2017.0646</a>","chicago":"Pleska, Maros, and Calin C Guet. “Effects of Mutations in Phage Restriction Sites during Escape from Restriction–Modification.” <i>Biology Letters</i>. The Royal Society, 2017. <a href=\"https://doi.org/10.1098/rsbl.2017.0646\">https://doi.org/10.1098/rsbl.2017.0646</a>."},"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1098/rsbl.2017.0646"}],"department":[{"_id":"CaGu"}],"status":"public","oa_version":"Published Version","language":[{"iso":"eng"}],"publist_id":"7253","doi":"10.1098/rsbl.2017.0646","isi":1,"title":"Effects of mutations in phage restriction sites during escape from restriction–modification","publication_status":"published","author":[{"first_name":"Maros","id":"4569785E-F248-11E8-B48F-1D18A9856A87","last_name":"Pleska","orcid":"0000-0001-7460-7479","full_name":"Pleska, Maros"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","last_name":"Guet","first_name":"Calin C","full_name":"Guet, Calin C"}],"pmid":1,"date_published":"2017-12-01T00:00:00Z","scopus_import":"1","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"}],"publication_identifier":{"issn":["1744-9561"]},"volume":13,"day":"01","ddc":["570"],"acknowledgement":"This work was funded by an HFSP Young Investigators' grant RGY0079/2011 (C.C.G.). M.P. is a recipient of a DOC Fellowship of the Austrian Academy of Science at the Institute of Science and Technology Austria.","publisher":"The Royal Society","corr_author":"1","article_processing_charge":"No","oa":1,"publication":"Biology Letters","external_id":{"pmid":["29237814"],"isi":["000418695400012"]},"month":"12","related_material":{"record":[{"status":"public","relation":"research_data","id":"9847"},{"relation":"dissertation_contains","status":"public","id":"202"}]},"type":"journal_article","article_type":"original","issue":"12","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","year":"2017","project":[{"grant_number":"RGY0079/2011","name":"Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification Systems","_id":"251BCBEC-B435-11E9-9278-68D0E5697425"},{"name":"Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level","_id":"251D65D8-B435-11E9-9278-68D0E5697425","grant_number":"24210"}],"fulldoi":"https://doi.org/10.1098/rsbl.2017.0646"},{"date_created":"2018-12-11T11:47:14Z","intvolume":"         6","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","image":"/images/cc_by.png","short":"CC BY (4.0)"},"date_updated":"2025-09-11T07:40:30Z","_id":"570","quality_controlled":"1","article_number":"e28921","oa_version":"Published Version","ec_funded":1,"language":[{"iso":"eng"}],"publist_id":"7244","citation":{"ieee":"M. Lagator, S. Sarikas, H. Acar, J. P. Bollback, and C. C. Guet, “Regulatory network structure determines patterns of intermolecular epistasis,” <i>eLife</i>, vol. 6. eLife Sciences Publications, 2017.","ista":"Lagator M, Sarikas S, Acar H, Bollback JP, Guet CC. 2017. Regulatory network structure determines patterns of intermolecular epistasis. eLife. 6, e28921.","ama":"Lagator M, Sarikas S, Acar H, Bollback JP, Guet CC. Regulatory network structure determines patterns of intermolecular epistasis. <i>eLife</i>. 2017;6. doi:<a href=\"https://doi.org/10.7554/eLife.28921\">10.7554/eLife.28921</a>","mla":"Lagator, Mato, et al. “Regulatory Network Structure Determines Patterns of Intermolecular Epistasis.” <i>ELife</i>, vol. 6, e28921, eLife Sciences Publications, 2017, doi:<a href=\"https://doi.org/10.7554/eLife.28921\">10.7554/eLife.28921</a>.","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.” <i>ELife</i>. eLife Sciences Publications, 2017. <a href=\"https://doi.org/10.7554/eLife.28921\">https://doi.org/10.7554/eLife.28921</a>.","apa":"Lagator, M., Sarikas, S., Acar, H., Bollback, J. P., &#38; Guet, C. C. (2017). Regulatory network structure determines patterns of intermolecular epistasis. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.28921\">https://doi.org/10.7554/eLife.28921</a>"},"department":[{"_id":"CaGu"},{"_id":"JoBo"},{"_id":"NiBa"}],"status":"public","file":[{"creator":"system","date_created":"2018-12-12T10:14:42Z","relation":"main_file","date_updated":"2020-07-14T12:47:10Z","checksum":"273ab17f33305e4eaafd911ff88e7c5b","content_type":"application/pdf","file_size":8453470,"file_id":"5096","access_level":"open_access","file_name":"IST-2017-918-v1+1_elife-28921-figures-v3.pdf"},{"file_id":"5097","access_level":"open_access","file_name":"IST-2017-918-v1+2_elife-28921-v3.pdf","date_created":"2018-12-12T10:14:43Z","creator":"system","checksum":"b433f90576c7be597cd43367946f8e7f","date_updated":"2020-07-14T12:47:10Z","relation":"main_file","file_size":1953221,"content_type":"application/pdf"}],"author":[{"first_name":"Mato","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","last_name":"Lagator","full_name":"Lagator, Mato"},{"full_name":"Sarikas, Srdjan","last_name":"Sarikas","id":"35F0286E-F248-11E8-B48F-1D18A9856A87","first_name":"Srdjan"},{"full_name":"Acar, Hande","id":"2DDF136A-F248-11E8-B48F-1D18A9856A87","last_name":"Acar","orcid":"0000-0003-1986-9753","first_name":"Hande"},{"full_name":"Bollback, Jonathan P","first_name":"Jonathan P","orcid":"0000-0002-4624-4612","last_name":"Bollback","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","last_name":"Guet","first_name":"Calin C","full_name":"Guet, Calin C"}],"date_published":"2017-11-13T00:00:00Z","publication_status":"published","doi":"10.7554/eLife.28921","title":"Regulatory network structure determines patterns of intermolecular epistasis","isi":1,"file_date_updated":"2020-07-14T12:47:10Z","pubrep_id":"918","ddc":["576"],"has_accepted_license":"1","corr_author":"1","publisher":"eLife Sciences Publications","scopus_import":"1","abstract":[{"lang":"eng","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. "}],"publication_identifier":{"issn":["2050-084X"]},"volume":6,"day":"13","month":"11","article_processing_charge":"No","oa":1,"external_id":{"isi":["000425868200001"]},"publication":"eLife","type":"journal_article","year":"2017","fulldoi":"https://doi.org/10.7554/eLife.28921","project":[{"grant_number":"291734","call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425","name":"International IST Postdoc Fellowship Programme"},{"grant_number":"648440","_id":"2578D616-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Selective Barriers to Horizontal Gene Transfer"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345"},{"pubrep_id":"911","file":[{"checksum":"44bb5d0229926c23a9955d9fe0f9723f","date_updated":"2020-07-14T12:47:20Z","relation":"main_file","date_created":"2018-12-12T10:16:05Z","creator":"system","file_size":1951699,"content_type":"application/pdf","access_level":"open_access","file_id":"5190","file_name":"IST-2017-911-v1+1_s41467-017-01683-1.pdf"}],"author":[{"full_name":"Chait, Remy P","first_name":"Remy P","last_name":"Chait","orcid":"0000-0003-0876-3187","id":"3464AE84-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Jakob","orcid":"0000-0003-1615-3282","last_name":"Ruess","id":"4A245D00-F248-11E8-B48F-1D18A9856A87","full_name":"Ruess, Jakob"},{"id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","last_name":"Bergmiller","orcid":"0000-0001-5396-4346","first_name":"Tobias","full_name":"Bergmiller, Tobias"},{"full_name":"Tkacik, Gasper","last_name":"Tkacik","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gasper"},{"full_name":"Guet, Calin C","first_name":"Calin C","orcid":"0000-0001-6220-2052","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"}],"date_published":"2017-12-01T00:00:00Z","publication_status":"published","doi":"10.1038/s41467-017-01683-1","title":"Shaping bacterial population behavior through computer interfaced control of individual cells","file_date_updated":"2020-07-14T12:47:20Z","isi":1,"language":[{"iso":"eng"}],"publist_id":"7191","oa_version":"Published Version","ec_funded":1,"status":"public","citation":{"ama":"Chait RP, Ruess J, Bergmiller T, Tkačik G, Guet CC. Shaping bacterial population behavior through computer interfaced control of individual cells. <i>Nature Communications</i>. 2017;8(1). doi:<a href=\"https://doi.org/10.1038/s41467-017-01683-1\">10.1038/s41467-017-01683-1</a>","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.","mla":"Chait, Remy P., et al. “Shaping Bacterial Population Behavior through Computer Interfaced Control of Individual Cells.” <i>Nature Communications</i>, vol. 8, no. 1, 1535, Nature Publishing Group, 2017, doi:<a href=\"https://doi.org/10.1038/s41467-017-01683-1\">10.1038/s41467-017-01683-1</a>.","ieee":"R. P. Chait, J. Ruess, T. Bergmiller, G. Tkačik, and C. C. Guet, “Shaping bacterial population behavior through computer interfaced control of individual cells,” <i>Nature Communications</i>, vol. 8, no. 1. Nature Publishing Group, 2017.","apa":"Chait, R. P., Ruess, J., Bergmiller, T., Tkačik, G., &#38; Guet, C. C. (2017). Shaping bacterial population behavior through computer interfaced control of individual cells. <i>Nature Communications</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/s41467-017-01683-1\">https://doi.org/10.1038/s41467-017-01683-1</a>","chicago":"Chait, Remy P, Jakob Ruess, Tobias Bergmiller, Gašper Tkačik, and Calin C Guet. “Shaping Bacterial Population Behavior through Computer Interfaced Control of Individual Cells.” <i>Nature Communications</i>. Nature Publishing Group, 2017. <a href=\"https://doi.org/10.1038/s41467-017-01683-1\">https://doi.org/10.1038/s41467-017-01683-1</a>.","short":"R.P. Chait, J. Ruess, T. Bergmiller, G. Tkačik, C.C. Guet, Nature Communications 8 (2017)."},"department":[{"_id":"CaGu"},{"_id":"GaTk"}],"_id":"613","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","image":"/images/cc_by.png","short":"CC BY (4.0)"},"date_updated":"2025-09-11T07:34:12Z","quality_controlled":"1","article_number":"1535","date_created":"2018-12-11T11:47:30Z","intvolume":"         8","year":"2017","fulldoi":"https://doi.org/10.1038/s41467-017-01683-1","project":[{"name":"International IST Postdoc Fellowship Programme","_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"291734"},{"call_identifier":"FWF","_id":"254E9036-B435-11E9-9278-68D0E5697425","name":"Biophysics of information processing in gene regulation","grant_number":"P28844-B27"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","issue":"1","type":"journal_article","month":"12","publication":"Nature Communications","external_id":{"isi":["000415323000008"]},"article_processing_charge":"Yes (in subscription journal)","oa":1,"corr_author":"1","publisher":"Nature Publishing Group","has_accepted_license":"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,"day":"01","scopus_import":"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."}],"publication_identifier":{"issn":["2041-1723"]}},{"author":[{"first_name":"Nela","id":"42D9CABC-F248-11E8-B48F-1D18A9856A87","last_name":"Nikolic","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","date_published":"2017-09-21T00:00:00Z","file":[{"checksum":"3d79ae6b6eabc90b0eaaed82ff3493b0","date_updated":"2020-07-14T12:47:24Z","relation":"main_file","date_created":"2018-12-12T10:11:51Z","creator":"system","content_type":"application/pdf","file_size":682064,"access_level":"open_access","file_id":"4908","file_name":"IST-2017-909-v1+1_peerj-3830.pdf"}],"doi":"10.7717/peerj.3830","title":"MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations","file_date_updated":"2020-07-14T12:47:24Z","isi":1,"pubrep_id":"909","date_created":"2018-12-11T11:47:33Z","intvolume":"      2017","_id":"624","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","image":"/images/cc_by.png","short":"CC BY (4.0)"},"date_updated":"2025-09-11T07:30:06Z","quality_controlled":"1","article_number":"3830","oa_version":"Published Version","language":[{"iso":"eng"}],"publist_id":"7172","citation":{"mla":"Nikolic, Nela, et al. “MazF Activation Promotes Translational Heterogeneity of the GrcA MRNA in Escherichia Coli Populations.” <i>PeerJ</i>, vol. 2017, no. 9, 3830, PeerJ, 2017, doi:<a href=\"https://doi.org/10.7717/peerj.3830\">10.7717/peerj.3830</a>.","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.","ama":"Nikolic N, Didara Z, Moll I. MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations. <i>PeerJ</i>. 2017;2017(9). doi:<a href=\"https://doi.org/10.7717/peerj.3830\">10.7717/peerj.3830</a>","ieee":"N. Nikolic, Z. Didara, and I. Moll, “MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations,” <i>PeerJ</i>, vol. 2017, no. 9. PeerJ, 2017.","chicago":"Nikolic, Nela, Zrinka Didara, and Isabella Moll. “MazF Activation Promotes Translational Heterogeneity of the GrcA MRNA in Escherichia Coli Populations.” <i>PeerJ</i>. PeerJ, 2017. <a href=\"https://doi.org/10.7717/peerj.3830\">https://doi.org/10.7717/peerj.3830</a>.","apa":"Nikolic, N., Didara, Z., &#38; Moll, I. (2017). MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations. <i>PeerJ</i>. PeerJ. <a href=\"https://doi.org/10.7717/peerj.3830\">https://doi.org/10.7717/peerj.3830</a>","short":"N. Nikolic, Z. Didara, I. Moll, PeerJ 2017 (2017)."},"department":[{"_id":"CaGu"}],"status":"public","type":"journal_article","year":"2017","fulldoi":"https://doi.org/10.7717/peerj.3830","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","issue":"9","has_accepted_license":"1","ddc":["579"],"acknowledgement":"Austrian Science Fund (FWF): M1697, P22249; Swiss National Science Foundation (SNF): 145706; European Commission;FWF Special Research Program: RNA-REG F43","publisher":"PeerJ","corr_author":"1","scopus_import":"1","abstract":[{"text":"Bacteria adapt to adverse environmental conditions by altering gene expression patterns. Recently, a novel stress adaptation mechanism has been described that allows Escherichia coli to alter gene expression at the post-transcriptional level. The key player in this regulatory pathway is the endoribonuclease MazF, the toxin component of the toxin-antitoxin module mazEF that is triggered by various stressful conditions. In general, MazF degrades the majority of transcripts by cleaving at ACA sites, which results in the retardation of bacterial growth. Furthermore, MazF can process a small subset of mRNAs and render them leaderless by removing their ribosome binding site. MazF concomitantly modifies ribosomes, making them selective for the translation of leaderless mRNAs. In this study, we employed fluorescent reporter-systems to investigate mazEF expression during stressful conditions, and to infer consequences of the mRNA processing mediated by MazF on gene expression at the single-cell level. Our results suggest that mazEF transcription is maintained at low levels in single cells encountering adverse conditions, such as antibiotic stress or amino acid starvation. Moreover, using the grcA mRNA as a model for MazF-mediated mRNA processing, we found that MazF activation promotes heterogeneity in the grcA reporter expression, resulting in a subpopulation of cells with increased levels of GrcA reporter protein.","lang":"eng"}],"publication_identifier":{"issn":["2167-8359"]},"volume":2017,"day":"21","month":"09","article_processing_charge":"No","oa":1,"publication":"PeerJ","external_id":{"isi":["000411665900002"]}},{"department":[{"_id":"CaGu"}],"citation":{"chicago":"Pleska, Maros. “Biology of Restriction-Modification Systems at the Single-Cell and Population Level.” Institute of Science and Technology Austria, 2017. <a href=\"https://doi.org/10.15479/AT:ISTA:th_916\">https://doi.org/10.15479/AT:ISTA:th_916</a>.","apa":"Pleska, M. (2017). <i>Biology of restriction-modification systems at the single-cell and population level</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:th_916\">https://doi.org/10.15479/AT:ISTA:th_916</a>","short":"M. Pleska, Biology of Restriction-Modification Systems at the Single-Cell and Population Level, Institute of Science and Technology Austria, 2017.","ista":"Pleska M. 2017. Biology of restriction-modification systems at the single-cell and population level. Institute of Science and Technology Austria.","ama":"Pleska M. Biology of restriction-modification systems at the single-cell and population level. 2017. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:th_916\">10.15479/AT:ISTA:th_916</a>","mla":"Pleska, Maros. <i>Biology of Restriction-Modification Systems at the Single-Cell and Population Level</i>. Institute of Science and Technology Austria, 2017, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:th_916\">10.15479/AT:ISTA:th_916</a>.","ieee":"M. Pleska, “Biology of restriction-modification systems at the single-cell and population level,” Institute of Science and Technology Austria, 2017."},"degree_awarded":"PhD","status":"public","oa_version":"Published Version","publist_id":"7711","language":[{"iso":"eng"}],"date_created":"2018-12-11T11:45:10Z","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","image":"/images/cc_by.png","short":"CC BY (4.0)"},"_id":"202","date_updated":"2026-06-18T18:54:19Z","alternative_title":["ISTA Thesis"],"pubrep_id":"916","file_date_updated":"2020-07-14T12:45:24Z","title":"Biology of restriction-modification systems at the single-cell and population level","doi":"10.15479/AT:ISTA:th_916","author":[{"orcid":"0000-0001-7460-7479","last_name":"Pleska","id":"4569785E-F248-11E8-B48F-1D18A9856A87","first_name":"Maros","full_name":"Pleska, Maros"}],"file":[{"content_type":"application/pdf","file_size":18569590,"date_created":"2018-12-12T10:08:48Z","creator":"system","checksum":"33cfb59674e91f82e3738396d3fb3776","date_updated":"2020-07-14T12:45:24Z","relation":"main_file","file_name":"IST-2018-916-v1+3_2017_Pleska_Maros_Thesis.pdf","file_id":"4710","access_level":"open_access"},{"file_name":"2017_Pleska_Maros_Thesis.docx","file_id":"6204","access_level":"closed","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_size":2801649,"creator":"dernst","date_created":"2019-04-05T08:33:14Z","relation":"source_file","checksum":"dcc239968decb233e7f98cf1083d8c26","date_updated":"2020-07-14T12:45:24Z"}],"date_published":"2017-10-01T00:00:00Z","publication_status":"published","page":"126","oa":1,"article_processing_charge":"No","OA_place":"publisher","related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"457"},{"relation":"part_of_dissertation","status":"public","id":"1243"},{"status":"public","relation":"part_of_dissertation","id":"561"}]},"month":"10","publication_identifier":{"issn":["2663-337X"]},"abstract":[{"text":"Restriction-modification (RM) represents the simplest and possibly the most widespread mechanism of self/non-self discrimination in nature. In order to provide bacteria with immunity against bacteriophages and other parasitic genetic elements, RM systems rely on a balance between two enzymes: the restriction enzyme, which cleaves non-self DNA at specific restriction sites, and the modification enzyme, which tags the host’s DNA as self and thus protects it from cleavage. In this thesis, I use population and single-cell level experiments in combination with mathematical modeling to study different aspects of the interplay between RM systems, bacteria and bacteriophages. First, I analyze how mutations in phage restriction sites affect the probability of phage escape – an inherently stochastic process, during which phages accidently get modified instead of restricted. Next, I use single-cell experiments to show that RM systems can, with a low probability, attack the genome of their bacterial host and that this primitive form of autoimmunity leads to a tradeoff between the evolutionary cost and benefit of RM systems. Finally, I investigate the nature of interactions between bacteria, RM systems and temperate bacteriophages to find that, as a consequence of phage escape and its impact on population dynamics, RM systems can promote acquisition of symbiotic bacteriophages, rather than limit it. The results presented here uncover new fundamental biological properties of RM systems and highlight their importance in the ecology and evolution of bacteria, bacteriophages and their interactions.","lang":"eng"}],"day":"01","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","has_accepted_license":"1","ddc":["576","579"],"corr_author":"1","publisher":"Institute of Science and Technology Austria","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","project":[{"name":"Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level","_id":"251D65D8-B435-11E9-9278-68D0E5697425","grant_number":"24210"}],"fulldoi":"https://doi.org/10.15479/AT:ISTA:th_916","supervisor":[{"full_name":"Guet, Calin C","first_name":"Calin C","orcid":"0000-0001-6220-2052","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"}],"year":"2017","type":"dissertation"},{"date_created":"2018-12-11T11:49:39Z","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","image":"/images/cc_by.png","short":"CC BY (4.0)"},"date_updated":"2025-04-15T06:50:01Z","_id":"1007","quality_controlled":"1","oa_version":"Published Version","ec_funded":1,"language":[{"iso":"eng"}],"publist_id":"6391","citation":{"ista":"Lang M, Sontag E. 2017. Zeros of nonlinear systems with input invariances. Automatica. 81C, 46–55.","ama":"Lang M, Sontag E. Zeros of nonlinear systems with input invariances. <i>Automatica</i>. 2017;81C:46-55. doi:<a href=\"https://doi.org/10.1016/j.automatica.2017.03.030\">10.1016/j.automatica.2017.03.030</a>","mla":"Lang, Moritz, and Eduardo Sontag. “Zeros of Nonlinear Systems with Input Invariances.” <i>Automatica</i>, vol. 81C, International Federation of Automatic Control, 2017, pp. 46–55, doi:<a href=\"https://doi.org/10.1016/j.automatica.2017.03.030\">10.1016/j.automatica.2017.03.030</a>.","ieee":"M. Lang and E. Sontag, “Zeros of nonlinear systems with input invariances,” <i>Automatica</i>, vol. 81C. International Federation of Automatic Control, pp. 46–55, 2017.","apa":"Lang, M., &#38; Sontag, E. (2017). Zeros of nonlinear systems with input invariances. <i>Automatica</i>. International Federation of Automatic Control. <a href=\"https://doi.org/10.1016/j.automatica.2017.03.030\">https://doi.org/10.1016/j.automatica.2017.03.030</a>","chicago":"Lang, Moritz, and Eduardo Sontag. “Zeros of Nonlinear Systems with Input Invariances.” <i>Automatica</i>. International Federation of Automatic Control, 2017. <a href=\"https://doi.org/10.1016/j.automatica.2017.03.030\">https://doi.org/10.1016/j.automatica.2017.03.030</a>.","short":"M. Lang, E. Sontag, Automatica 81C (2017) 46–55."},"department":[{"_id":"CaGu"},{"_id":"GaTk"}],"status":"public","page":"46 - 55","publication_status":"published","file":[{"file_id":"4884","access_level":"open_access","file_name":"IST-2017-813-v1+1_ZerosOfNonlinearSystems.pdf","creator":"system","date_created":"2018-12-12T10:11:29Z","relation":"main_file","date_updated":"2018-12-12T10:11:29Z","file_size":1401954,"content_type":"application/pdf"}],"date_published":"2017-06-01T00:00:00Z","author":[{"first_name":"Moritz","last_name":"Lang","id":"29E0800A-F248-11E8-B48F-1D18A9856A87","full_name":"Lang, Moritz"},{"first_name":"Eduardo","last_name":"Sontag","full_name":"Sontag, Eduardo"}],"doi":"10.1016/j.automatica.2017.03.030","title":"Zeros of nonlinear systems with input invariances","isi":1,"file_date_updated":"2018-12-12T10:11:29Z","pubrep_id":"813","ddc":["000"],"has_accepted_license":"1","publisher":"International Federation of Automatic Control","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) -&gt; u(t) + p, p in R) or scale-invariance (u(t) -&gt; pu(t), p in R&gt;0). In this article, we introduce the concept of s0-invariances with respect to continuous input transformations exponentially growing/decaying over time. We show that s0-invariant systems not only encompass linear time-invariant (LTI) systems with transfer functions having an irreducible zero at s0 in R, but also that the input/output relationship of nonlinear s0-invariant systems possesses properties well known from their linear counterparts. Furthermore, we extend the concept of s0-invariances to second- and higher-order s0-invariances, corresponding to invariances with respect to transformations of the time-derivatives of the input, and encompassing LTI systems with zeros of multiplicity two or higher. Finally, we show that nth-order 0-invariant systems realize – under mild conditions – nth-order nonlinear differential operators: when excited by an input of a characteristic functional form, the system’s output converges to a constant value only depending on the nth (nonlinear) derivative of the input.","lang":"eng"}],"scopus_import":"1","publication_identifier":{"issn":["0005-1098"]},"volume":"81C","day":"01","month":"06","article_processing_charge":"Yes (in subscription journal)","oa":1,"publication":"Automatica","external_id":{"isi":["000403513900006"]},"type":"journal_article","year":"2017","project":[{"_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme","grant_number":"291734"}],"fulldoi":"https://doi.org/10.1016/j.automatica.2017.03.030","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"},{"publication_status":"published","file":[{"access_level":"open_access","file_id":"5306","file_name":"IST-2017-841-v1+1_elife-25192-v2.pdf","date_updated":"2020-07-14T12:48:16Z","checksum":"59cdd4400fb41280122d414fea971546","relation":"main_file","date_created":"2018-12-12T10:17:49Z","creator":"system","file_size":2441529,"content_type":"application/pdf"},{"access_level":"open_access","file_id":"5307","file_name":"IST-2017-841-v1+2_elife-25192-figures-v2.pdf","checksum":"b69024880558b858eb8c5d47a92b6377","date_updated":"2020-07-14T12:48:16Z","relation":"main_file","date_created":"2018-12-12T10:17:50Z","creator":"system","content_type":"application/pdf","file_size":3752660}],"author":[{"first_name":"Mato","last_name":"Lagator","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","full_name":"Lagator, Mato"},{"full_name":"Paixao, Tiago","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2361-3953","last_name":"Paixao","first_name":"Tiago"},{"full_name":"Barton, Nicholas H","first_name":"Nicholas H","orcid":"0000-0002-8548-5240","last_name":"Barton","id":"4880FE40-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Bollback, Jonathan P","first_name":"Jonathan P","last_name":"Bollback","orcid":"0000-0002-4624-4612","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","last_name":"Guet","first_name":"Calin C","full_name":"Guet, Calin C"}],"date_published":"2017-05-18T00:00:00Z","file_date_updated":"2020-07-14T12:48:16Z","title":"On the mechanistic nature of epistasis in a canonical cis-regulatory element","isi":1,"doi":"10.7554/eLife.25192","pubrep_id":"841","intvolume":"         6","date_created":"2018-12-11T11:49:23Z","quality_controlled":"1","article_number":"e25192","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","image":"/images/cc_by.png","short":"CC BY (4.0)"},"_id":"954","date_updated":"2025-07-10T12:01:50Z","ec_funded":1,"oa_version":"Published Version","publist_id":"6460","language":[{"iso":"eng"}],"department":[{"_id":"CaGu"},{"_id":"NiBa"},{"_id":"JoBo"}],"citation":{"ieee":"M. Lagator, T. Paixao, N. H. Barton, J. P. Bollback, and C. C. Guet, “On the mechanistic nature of epistasis in a canonical cis-regulatory element,” <i>eLife</i>, vol. 6. eLife Sciences Publications, 2017.","mla":"Lagator, Mato, et al. “On the Mechanistic Nature of Epistasis in a Canonical Cis-Regulatory Element.” <i>ELife</i>, vol. 6, e25192, eLife Sciences Publications, 2017, doi:<a href=\"https://doi.org/10.7554/eLife.25192\">10.7554/eLife.25192</a>.","ista":"Lagator M, Paixao T, Barton NH, Bollback JP, Guet CC. 2017. On the mechanistic nature of epistasis in a canonical cis-regulatory element. eLife. 6, e25192.","ama":"Lagator M, Paixao T, Barton NH, Bollback JP, Guet CC. On the mechanistic nature of epistasis in a canonical cis-regulatory element. <i>eLife</i>. 2017;6. doi:<a href=\"https://doi.org/10.7554/eLife.25192\">10.7554/eLife.25192</a>","short":"M. Lagator, T. Paixao, N.H. Barton, J.P. Bollback, C.C. Guet, ELife 6 (2017).","chicago":"Lagator, Mato, Tiago Paixao, Nicholas H Barton, Jonathan P Bollback, and Calin C Guet. “On the Mechanistic Nature of Epistasis in a Canonical Cis-Regulatory Element.” <i>ELife</i>. eLife Sciences Publications, 2017. <a href=\"https://doi.org/10.7554/eLife.25192\">https://doi.org/10.7554/eLife.25192</a>.","apa":"Lagator, M., Paixao, T., Barton, N. H., Bollback, J. P., &#38; Guet, C. C. (2017). On the mechanistic nature of epistasis in a canonical cis-regulatory element. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.25192\">https://doi.org/10.7554/eLife.25192</a>"},"status":"public","type":"journal_article","project":[{"grant_number":"618091","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation"},{"name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734"},{"name":"Selective Barriers to Horizontal Gene Transfer","_id":"2578D616-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"648440"}],"fulldoi":"https://doi.org/10.7554/eLife.25192","year":"2017","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","has_accepted_license":"1","ddc":["576"],"publisher":"eLife Sciences Publications","publication_identifier":{"issn":["2050-084X"]},"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"}],"scopus_import":"1","day":"18","volume":6,"month":"05","oa":1,"article_processing_charge":"Yes","publication":"eLife","external_id":{"isi":["000404024800001"]}},{"type":"journal_article","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","year":"2017","fulldoi":"https://doi.org/10.7554/eLife.23136","volume":6,"day":"06","scopus_import":"1","abstract":[{"text":"The bacterial flagellum is a self-assembling nanomachine. The external flagellar filament, several times longer than a bacterial cell body, is made of a few tens of thousands subunits of a single protein: flagellin. A fundamental problem concerns the molecular mechanism of how the flagellum grows outside the cell, where no discernible energy source is available. Here, we monitored the dynamic assembly of individual flagella using in situ labelling and real-time immunostaining of elongating flagellar filaments. We report that the rate of flagellum growth, initially ~1,700 amino acids per second, decreases with length and that the previously proposed chain mechanism does not contribute to the filament elongation dynamics. Inhibition of the proton motive force-dependent export apparatus revealed a major contribution of substrate injection in driving filament elongation. The combination of experimental and mathematical evidence demonstrates that a simple, injection-diffusion mechanism controls bacterial flagella growth outside the cell.","lang":"eng"}],"publication_identifier":{"issn":["2050-084X"]},"publisher":"eLife Sciences Publications","has_accepted_license":"1","ddc":["579"],"publication":"eLife","external_id":{"isi":["000398680700001"]},"article_processing_charge":"No","oa":1,"month":"03","doi":"10.7554/eLife.23136","title":"Bacterial flagella grow through an injection diffusion mechanism","file_date_updated":"2020-07-14T12:47:33Z","isi":1,"author":[{"full_name":"Renault, Thibaud","first_name":"Thibaud","last_name":"Renault"},{"last_name":"Abraham","first_name":"Anthony","full_name":"Abraham, Anthony"},{"full_name":"Bergmiller, Tobias","first_name":"Tobias","orcid":"0000-0001-5396-4346","last_name":"Bergmiller","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Paradis","first_name":"Guillaume","full_name":"Paradis, Guillaume"},{"full_name":"Rainville, Simon","last_name":"Rainville","first_name":"Simon"},{"last_name":"Charpentier","first_name":"Emmanuelle","full_name":"Charpentier, Emmanuelle"},{"orcid":"0000-0001-6220-2052","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","full_name":"Guet, Calin C"},{"full_name":"Tu, Yuhai","first_name":"Yuhai","last_name":"Tu"},{"full_name":"Namba, Keiichi","last_name":"Namba","first_name":"Keiichi"},{"full_name":"Keener, James","first_name":"James","last_name":"Keener"},{"full_name":"Minamino, Tohru","first_name":"Tohru","last_name":"Minamino"},{"full_name":"Erhardt, Marc","first_name":"Marc","last_name":"Erhardt"}],"publication_status":"published","date_published":"2017-03-06T00:00:00Z","file":[{"file_name":"IST-2017-904-v1+1_elife-23136-v2.pdf","access_level":"open_access","file_id":"4716","file_size":5520359,"content_type":"application/pdf","date_updated":"2020-07-14T12:47:33Z","checksum":"39e1c3e82ddac83a30422fa72fa1a383","relation":"main_file","date_created":"2018-12-12T10:08:53Z","creator":"system"},{"date_created":"2018-12-12T10:08:54Z","creator":"system","checksum":"a6d542253028f52e00aa29739ddffe8f","date_updated":"2020-07-14T12:47:33Z","relation":"main_file","file_size":11242920,"content_type":"application/pdf","file_id":"4717","access_level":"open_access","file_name":"IST-2017-904-v1+2_elife-23136-figures-v2.pdf"}],"pubrep_id":"904","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","image":"/images/cc_by.png","short":"CC BY (4.0)"},"_id":"655","date_updated":"2025-09-11T07:11:19Z","article_number":"e23136","quality_controlled":"1","date_created":"2018-12-11T11:47:44Z","intvolume":"         6","status":"public","citation":{"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.” <i>ELife</i>. eLife Sciences Publications, 2017. <a href=\"https://doi.org/10.7554/eLife.23136\">https://doi.org/10.7554/eLife.23136</a>.","apa":"Renault, T., Abraham, A., Bergmiller, T., Paradis, G., Rainville, S., Charpentier, E., … Erhardt, M. (2017). Bacterial flagella grow through an injection diffusion mechanism. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.23136\">https://doi.org/10.7554/eLife.23136</a>","ieee":"T. Renault <i>et al.</i>, “Bacterial flagella grow through an injection diffusion mechanism,” <i>eLife</i>, vol. 6. eLife Sciences Publications, 2017.","mla":"Renault, Thibaud, et al. “Bacterial Flagella Grow through an Injection Diffusion Mechanism.” <i>ELife</i>, vol. 6, e23136, eLife Sciences Publications, 2017, doi:<a href=\"https://doi.org/10.7554/eLife.23136\">10.7554/eLife.23136</a>.","ista":"Renault T, Abraham A, Bergmiller T, Paradis G, Rainville S, Charpentier E, Guet CC, Tu Y, Namba K, Keener J, Minamino T, Erhardt M. 2017. Bacterial flagella grow through an injection diffusion mechanism. eLife. 6, e23136.","ama":"Renault T, Abraham A, Bergmiller T, et al. Bacterial flagella grow through an injection diffusion mechanism. <i>eLife</i>. 2017;6. doi:<a href=\"https://doi.org/10.7554/eLife.23136\">10.7554/eLife.23136</a>"},"department":[{"_id":"CaGu"}],"language":[{"iso":"eng"}],"publist_id":"7082","oa_version":"Published Version"},{"day":"21","volume":356,"publication_identifier":{"issn":["0036-8075"]},"scopus_import":"1","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"}],"publisher":"American Association for the Advancement of Science","corr_author":"1","publication":"Science","external_id":{"isi":["000399540100060"]},"article_processing_charge":"No","related_material":{"record":[{"status":"public","relation":"popular_science","id":"5560"}]},"month":"04","type":"journal_article","article_type":"original","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","issue":"6335","project":[{"_id":"254E9036-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Biophysics of information processing in gene regulation","grant_number":"P28844-B27"}],"fulldoi":"https://doi.org/10.1126/science.aaf4762","year":"2017","quality_controlled":"1","_id":"665","date_updated":"2025-09-11T07:05:04Z","intvolume":"       356","date_created":"2018-12-11T11:47:48Z","status":"public","department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"Bio"}],"citation":{"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. <i>Science</i>. American Association for the Advancement of Science. <a href=\"https://doi.org/10.1126/science.aaf4762\">https://doi.org/10.1126/science.aaf4762</a>","chicago":"Bergmiller, Tobias, Anna M Andersson, Kathrin Tomasek, Enrique Balleza, Daniel Kiviet, Robert Hauschild, Gašper Tkačik, and Calin C Guet. “Biased Partitioning of the Multidrug Efflux Pump AcrAB TolC Underlies Long Lived Phenotypic Heterogeneity.” <i>Science</i>. American Association for the Advancement of Science, 2017. <a href=\"https://doi.org/10.1126/science.aaf4762\">https://doi.org/10.1126/science.aaf4762</a>.","short":"T. Bergmiller, A.M. Andersson, K. Tomasek, E. Balleza, D. Kiviet, R. Hauschild, G. Tkačik, C.C. Guet, Science 356 (2017) 311–315.","mla":"Bergmiller, Tobias, et al. “Biased Partitioning of the Multidrug Efflux Pump AcrAB TolC Underlies Long Lived Phenotypic Heterogeneity.” <i>Science</i>, vol. 356, no. 6335, American Association for the Advancement of Science, 2017, pp. 311–15, doi:<a href=\"https://doi.org/10.1126/science.aaf4762\">10.1126/science.aaf4762</a>.","ama":"Bergmiller T, Andersson AM, Tomasek K, et al. Biased partitioning of the multidrug efflux pump AcrAB TolC underlies long lived phenotypic heterogeneity. <i>Science</i>. 2017;356(6335):311-315. doi:<a href=\"https://doi.org/10.1126/science.aaf4762\">10.1126/science.aaf4762</a>","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.","ieee":"T. Bergmiller <i>et al.</i>, “Biased partitioning of the multidrug efflux pump AcrAB TolC underlies long lived phenotypic heterogeneity,” <i>Science</i>, vol. 356, no. 6335. American Association for the Advancement of Science, pp. 311–315, 2017."},"publist_id":"7064","language":[{"iso":"eng"}],"oa_version":"None","title":"Biased partitioning of the multidrug efflux pump AcrAB TolC underlies long lived phenotypic heterogeneity","isi":1,"doi":"10.1126/science.aaf4762","date_published":"2017-04-21T00:00:00Z","author":[{"full_name":"Bergmiller, Tobias","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5396-4346","last_name":"Bergmiller","first_name":"Tobias"},{"full_name":"Andersson, Anna M","id":"2B8A40DA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2912-6769","last_name":"Andersson","first_name":"Anna M"},{"first_name":"Kathrin","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","last_name":"Tomasek","orcid":"0000-0003-3768-877X","full_name":"Tomasek, Kathrin"},{"last_name":"Balleza","first_name":"Enrique","full_name":"Balleza, Enrique"},{"full_name":"Kiviet, Daniel","first_name":"Daniel","last_name":"Kiviet"},{"orcid":"0000-0001-9843-3522","last_name":"Hauschild","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","first_name":"Robert","full_name":"Hauschild, Robert"},{"full_name":"Tkacik, Gasper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","last_name":"Tkacik","orcid":"0000-0002-6699-1455","first_name":"Gasper"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","orcid":"0000-0001-6220-2052","first_name":"Calin C","full_name":"Guet, Calin C"}],"publication_status":"published","page":"311 - 315"}]