[{"file_date_updated":"2022-12-20T23:30:05Z","page":"73","day":"18","type":"dissertation","status":"public","supervisor":[{"full_name":"Sixt, Michael K","last_name":"Sixt","orcid":"0000-0002-4561-241X","first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Calin C","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"}],"degree_awarded":"PhD","has_accepted_license":"1","department":[{"_id":"MiSi"},{"_id":"CaGu"},{"_id":"GradSch"}],"file":[{"file_id":"10308","creator":"ktomasek","relation":"main_file","content_type":"application/pdf","checksum":"b39c9e0ef18d0484d537a67551effd02","date_created":"2021-11-18T15:07:31Z","embargo":"2022-11-18","file_size":13266088,"file_name":"ThesisTomasekKathrin.pdf","access_level":"open_access","date_updated":"2022-12-20T23:30:05Z"},{"file_size":7539509,"file_name":"ThesisTomasekKathrin.docx","checksum":"c0c440ee9e5ef1102a518a4f9f023e7c","date_created":"2021-11-18T15:07:46Z","embargo_to":"open_access","access_level":"closed","date_updated":"2022-12-20T23:30:05Z","relation":"source_file","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_id":"10309","creator":"ktomasek"}],"date_created":"2021-11-18T15:05:06Z","month":"11","date_published":"2021-11-18T00:00:00Z","publisher":"Institute of Science and Technology Austria","language":[{"iso":"eng"}],"date_updated":"2023-09-07T13:34:38Z","oa":1,"article_processing_charge":"No","_id":"10307","publication_identifier":{"issn":["2663-337X"]},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa_version":"Published Version","publication_status":"published","citation":{"ista":"Tomasek K. 2021. Pathogenic Escherichia coli hijack the host immune response. Institute of Science and Technology Austria.","short":"K. Tomasek, Pathogenic Escherichia Coli Hijack the Host Immune Response, Institute of Science and Technology Austria, 2021.","ama":"Tomasek K. Pathogenic Escherichia coli hijack the host immune response. 2021. doi:<a href=\"https://doi.org/10.15479/at:ista:10307\">10.15479/at:ista:10307</a>","mla":"Tomasek, Kathrin. <i>Pathogenic Escherichia Coli Hijack the Host Immune Response</i>. Institute of Science and Technology Austria, 2021, doi:<a href=\"https://doi.org/10.15479/at:ista:10307\">10.15479/at:ista:10307</a>.","chicago":"Tomasek, Kathrin. “Pathogenic Escherichia Coli Hijack the Host Immune Response.” Institute of Science and Technology Austria, 2021. <a href=\"https://doi.org/10.15479/at:ista:10307\">https://doi.org/10.15479/at:ista:10307</a>.","apa":"Tomasek, K. (2021). <i>Pathogenic Escherichia coli hijack the host immune response</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:10307\">https://doi.org/10.15479/at:ista:10307</a>","ieee":"K. Tomasek, “Pathogenic Escherichia coli hijack the host immune response,” Institute of Science and Technology Austria, 2021."},"abstract":[{"lang":"eng","text":"Bacteria-host interactions represent a continuous trade-off between benefit and risk. Thus, the host immune response is faced with a non-trivial problem – accommodate beneficial commensals and remove harmful pathogens. This is especially difficult as molecular patterns, such as lipopolysaccharide or specific surface organelles such as pili, are conserved in both, commensal and pathogenic bacteria. Type 1 pili, tightly regulated by phase variation, are considered an important virulence factor of pathogenic bacteria as they facilitate invasion into host cells. While invasion represents a de facto passive mechanism for pathogens to escape the host immune response, we demonstrate a fundamental role of type 1 pili as active modulators of the innate and adaptive immune response."}],"author":[{"id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","first_name":"Kathrin","full_name":"Tomasek, Kathrin","last_name":"Tomasek","orcid":"0000-0003-3768-877X"}],"alternative_title":["ISTA Thesis"],"related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"10316"}]},"ddc":["570"],"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"doi":"10.15479/at:ista:10307","year":"2021","title":"Pathogenic Escherichia coli hijack the host immune response"},{"doi":"10.15479/AT:ISTA:8155","year":"2020","title":"Gene regulation across scales – how biophysical constraints shape evolution","alternative_title":["ISTA Thesis"],"ddc":["530","570"],"related_material":{"record":[{"status":"public","id":"7675","relation":"part_of_dissertation"},{"relation":"part_of_dissertation","id":"7569","status":"public"},{"status":"public","id":"7652","relation":"part_of_dissertation"}]},"citation":{"ama":"Grah R. Gene regulation across scales – how biophysical constraints shape evolution. 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8155\">10.15479/AT:ISTA:8155</a>","mla":"Grah, Rok. <i>Gene Regulation across Scales – How Biophysical Constraints Shape Evolution</i>. Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8155\">10.15479/AT:ISTA:8155</a>.","short":"R. Grah, Gene Regulation across Scales – How Biophysical Constraints Shape Evolution, Institute of Science and Technology Austria, 2020.","ista":"Grah R. 2020. Gene regulation across scales – how biophysical constraints shape evolution. Institute of Science and Technology Austria.","ieee":"R. Grah, “Gene regulation across scales – how biophysical constraints shape evolution,” Institute of Science and Technology Austria, 2020.","apa":"Grah, R. (2020). <i>Gene regulation across scales – how biophysical constraints shape evolution</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:8155\">https://doi.org/10.15479/AT:ISTA:8155</a>","chicago":"Grah, Rok. “Gene Regulation across Scales – How Biophysical Constraints Shape Evolution.” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:8155\">https://doi.org/10.15479/AT:ISTA:8155</a>."},"publication_status":"published","author":[{"full_name":"Grah, Rok","last_name":"Grah","orcid":"0000-0003-2539-3560","first_name":"Rok","id":"483E70DE-F248-11E8-B48F-1D18A9856A87"}],"abstract":[{"lang":"eng","text":"In the thesis we focus on the interplay of the biophysics and evolution of gene regulation. We start by addressing how the type of prokaryotic gene regulation – activation and repression – affects spurious binding to DNA, also known as\r\ntranscriptional crosstalk. We propose that regulatory interference caused by excess regulatory proteins in the dense cellular medium – global crosstalk – could be a factor in determining which type of gene regulatory network is evolutionarily preferred. Next,we use a normative approach in eukaryotic gene regulation to describe minimal\r\nnon-equilibrium enhancer models that optimize so-called regulatory phenotypes. We find a class of models that differ from standard thermodynamic equilibrium models by a single parameter that notably increases the regulatory performance. Next chapter addresses the question of genotype-phenotype-fitness maps of higher dimensional phenotypes. We show that our biophysically realistic approach allows us to understand how the mechanisms of promoter function constrain genotypephenotype maps, and how they affect the evolutionary trajectories of promoters.\r\nIn the last chapter we ask whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. Using mathematical modeling, we show that amplifications can tune gene expression in many environments, including those where transcription factor-based schemes are\r\nhard to evolve or maintain. "}],"article_processing_charge":"No","date_updated":"2023-09-07T13:13:27Z","oa":1,"oa_version":"Published Version","project":[{"_id":"267C84F4-B435-11E9-9278-68D0E5697425","name":"Biophysically realistic genotype-phenotype maps for regulatory networks"}],"acknowledgement":"For the duration of his PhD, Rok was a recipient of a DOC fellowship of the Austrian Academy of Sciences.","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","publication_identifier":{"issn":["2663-337X"]},"_id":"8155","date_published":"2020-07-24T00:00:00Z","month":"07","language":[{"iso":"eng"}],"publisher":"Institute of Science and Technology Austria","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"has_accepted_license":"1","degree_awarded":"PhD","file":[{"content_type":"application/pdf","relation":"main_file","file_id":"8176","creator":"rgrah","success":1,"date_updated":"2020-07-27T12:00:07Z","access_level":"open_access","file_name":"Thesis_RokGrah_200727_convertedNew.pdf","file_size":16638998,"date_created":"2020-07-27T12:00:07Z"},{"creator":"rgrah","file_id":"8177","content_type":"application/zip","relation":"main_file","date_created":"2020-07-27T12:02:23Z","file_name":"Thesis_new.zip","file_size":347459978,"date_updated":"2020-07-30T13:04:55Z","access_level":"closed"}],"date_created":"2020-07-23T09:51:28Z","type":"dissertation","day":"24","status":"public","supervisor":[{"first_name":"Calin C","full_name":"Guet, Calin C","last_name":"Guet","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Gašper","orcid":"0000-0002-6699-1455","last_name":"Tkačik","full_name":"Tkačik, Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"}],"file_date_updated":"2020-07-30T13:04:55Z","page":"310"},{"status":"public","supervisor":[{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","first_name":"Calin C"}],"type":"dissertation","day":"13","page":"117","file_date_updated":"2021-10-20T22:30:03Z","language":[{"iso":"eng"}],"publisher":"Institute of Science and Technology Austria","date_published":"2020-10-13T00:00:00Z","month":"10","date_created":"2020-10-13T13:02:33Z","file":[{"file_id":"8666","creator":"itomanek","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","relation":"source_file","date_created":"2020-10-16T12:14:21Z","checksum":"c01d9f59794b4b70528f37637c17ad02","file_name":"Thesis_ITomanek_final_201016.docx","file_size":25131884,"date_updated":"2021-10-20T22:30:03Z","access_level":"closed","embargo_to":"open_access"},{"creator":"itomanek","file_id":"8667","content_type":"application/pdf","relation":"main_file","date_created":"2020-10-16T12:14:21Z","checksum":"f8edbc3b0f81a780e13ca1e561d42d8b","file_name":"Thesis_ITomanek_final_201016.pdf","file_size":15405675,"embargo":"2021-10-19","date_updated":"2021-10-20T22:30:03Z","access_level":"open_access"}],"department":[{"_id":"CaGu"}],"has_accepted_license":"1","degree_awarded":"PhD","author":[{"full_name":"Tomanek, Isabella","last_name":"Tomanek","orcid":"0000-0001-6197-363X","first_name":"Isabella","id":"3981F020-F248-11E8-B48F-1D18A9856A87"}],"keyword":["duplication","amplification","promoter","CNV","AMGET","experimental evolution","Escherichia coli"],"abstract":[{"text":"Mutations are the raw material of evolution and come in many different flavors. Point mutations change a single letter in the DNA sequence, while copy number mutations like duplications or deletions add or remove many letters of the DNA sequence simultaneously.  Each type of mutation exhibits specific properties like its rate of formation and reversal. \r\nGene expression is a fundamental phenotype that can be altered by both, point and copy number mutations. The following thesis is concerned with the dynamics of gene expression evolution and how it is affected by the properties exhibited by point and copy number mutations. Specifically, we are considering i) copy number mutations during adaptation to fluctuating environments and ii) the interaction of copy number and point mutations during adaptation to constant environments.  ","lang":"eng"}],"publication_status":"published","citation":{"mla":"Tomanek, Isabella. <i>The Evolution of Gene Expression by Copy Number and Point Mutations</i>. Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8653\">10.15479/AT:ISTA:8653</a>.","ama":"Tomanek I. The evolution of gene expression by copy number and point mutations. 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8653\">10.15479/AT:ISTA:8653</a>","short":"I. Tomanek, The Evolution of Gene Expression by Copy Number and Point Mutations, Institute of Science and Technology Austria, 2020.","ista":"Tomanek I. 2020. The evolution of gene expression by copy number and point mutations. Institute of Science and Technology Austria.","apa":"Tomanek, I. (2020). <i>The evolution of gene expression by copy number and point mutations</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:8653\">https://doi.org/10.15479/AT:ISTA:8653</a>","ieee":"I. Tomanek, “The evolution of gene expression by copy number and point mutations,” Institute of Science and Technology Austria, 2020.","chicago":"Tomanek, Isabella. “The Evolution of Gene Expression by Copy Number and Point Mutations.” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:8653\">https://doi.org/10.15479/AT:ISTA:8653</a>."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa_version":"Published Version","_id":"8653","publication_identifier":{"issn":["2663-337X"]},"date_updated":"2023-09-07T13:22:42Z","oa":1,"article_processing_charge":"No","title":"The evolution of gene expression by copy number and point mutations","doi":"10.15479/AT:ISTA:8653","year":"2020","ddc":["576"],"related_material":{"record":[{"status":"public","id":"7652","relation":"research_data"}]},"alternative_title":["ISTA Thesis"]},{"title":"On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation","doi":"10.15479/AT:ISTA:6371","year":"2019","ddc":["576","579"],"related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"67"},{"status":"public","relation":"popular_science","id":"5585"}]},"alternative_title":["ISTA Thesis"],"author":[{"first_name":"Claudia","full_name":"Igler, Claudia","last_name":"Igler","id":"46613666-F248-11E8-B48F-1D18A9856A87"}],"keyword":["gene regulation","biophysics","transcription factor binding","bacteria"],"abstract":[{"text":"Decades of studies have revealed the mechanisms of gene regulation in molecular detail. We make use of such well-described regulatory systems to explore how the molecular mechanisms of protein-protein and protein-DNA interactions shape the dynamics and evolution of gene regulation. \r\n\r\ni) We uncover how the biophysics of protein-DNA binding determines the potential of regulatory networks to evolve and adapt, which can be captured using a simple mathematical model. \r\nii) The evolution of regulatory connections can lead to a significant amount of crosstalk between binding proteins. We explore the effect of crosstalk on gene expression from a target promoter, which seems to be modulated through binding competition at non-specific DNA sites. \r\niii) We investigate how the very same biophysical characteristics as in i) can generate significant fitness costs for cells through global crosstalk, meaning non-specific DNA binding across the genomic background. \r\niv) Binding competition between proteins at a target promoter is a prevailing regulatory feature due to the prevalence of co-regulation at bacterial promoters. However, the dynamics of these systems are not always straightforward to determine even if the molecular mechanisms of regulation are known. A detailed model of the biophysical interactions reveals that interference between the regulatory proteins can constitute a new, generic form of system memory that records the history of the input signals at the promoter. \r\n\r\nWe demonstrate how the biophysics of protein-DNA binding can be harnessed to investigate the principles that shape and ultimately limit cellular gene regulation. These results provide a basis for studies of higher-level functionality, which arises from the underlying regulation.   \r\n","lang":"eng"}],"publication_status":"published","citation":{"chicago":"Igler, Claudia. “On the Nature of Gene Regulatory Design - The Biophysics of Transcription Factor Binding Shapes Gene Regulation.” Institute of Science and Technology Austria, 2019. <a href=\"https://doi.org/10.15479/AT:ISTA:6371\">https://doi.org/10.15479/AT:ISTA:6371</a>.","ieee":"C. Igler, “On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation,” Institute of Science and Technology Austria, 2019.","apa":"Igler, C. (2019). <i>On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:6371\">https://doi.org/10.15479/AT:ISTA:6371</a>","ista":"Igler C. 2019. On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation. Institute of Science and Technology Austria.","short":"C. Igler, On the Nature of Gene Regulatory Design - The Biophysics of Transcription Factor Binding Shapes Gene Regulation, Institute of Science and Technology Austria, 2019.","ama":"Igler C. On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation. 2019. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6371\">10.15479/AT:ISTA:6371</a>","mla":"Igler, Claudia. <i>On the Nature of Gene Regulatory Design - The Biophysics of Transcription Factor Binding Shapes Gene Regulation</i>. Institute of Science and Technology Austria, 2019, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6371\">10.15479/AT:ISTA:6371</a>."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","project":[{"grant_number":"24573","_id":"251EE76E-B435-11E9-9278-68D0E5697425","name":"Design principles underlying genetic switch architecture (DOC Fellowship)"}],"oa_version":"Published Version","_id":"6371","publication_identifier":{"issn":["2663-337X"]},"date_updated":"2024-02-21T13:45:52Z","oa":1,"article_processing_charge":"No","language":[{"iso":"eng"}],"publisher":"Institute of Science and Technology Austria","date_published":"2019-05-03T00:00:00Z","month":"05","date_created":"2019-05-03T11:55:51Z","file":[{"relation":"main_file","content_type":"application/pdf","creator":"cigler","file_id":"6373","file_size":12597663,"embargo":"2020-05-02","file_name":"IglerClaudia_OntheNatureofGeneRegulatoryDesign.pdf","checksum":"c0085d47c58c9cbcab1b0a783480f6da","date_created":"2019-05-03T11:54:52Z","access_level":"open_access","date_updated":"2021-02-11T11:17:13Z"},{"file_size":34644426,"file_name":"IglerClaudia_OntheNatureofGeneRegulatoryDesign.docx","checksum":"2eac954de1c8bbf7e6fb35ed0221ae8c","date_created":"2019-05-03T11:54:54Z","embargo_to":"open_access","access_level":"closed","date_updated":"2020-07-14T12:47:28Z","relation":"source_file","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_id":"6374","creator":"cigler"}],"department":[{"_id":"CaGu"}],"has_accepted_license":"1","degree_awarded":"PhD","status":"public","supervisor":[{"first_name":"Calin C","full_name":"Guet, Calin C","last_name":"Guet","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"}],"type":"dissertation","day":"03","page":"152","file_date_updated":"2021-02-11T11:17:13Z"},{"year":"2018","doi":"10.15479/AT:ISTA:th1059","pubrep_id":"1059","title":"The influence of sequence context on the evolution of bacterial gene expression","alternative_title":["ISTA Thesis"],"related_material":{"record":[{"relation":"part_of_dissertation","id":"704","status":"public"}]},"ddc":["576","579"],"publication_status":"published","citation":{"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>.","ieee":"M. Steinrück, “The influence of sequence context on the evolution of bacterial gene expression,” Institute of Science and Technology Austria, 2018.","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>","short":"M. Steinrück, The Influence of Sequence Context on the Evolution of Bacterial Gene Expression, Institute of Science and Technology Austria, 2018.","ista":"Steinrück M. 2018. The influence of sequence context on the evolution of bacterial gene expression. Institute of Science and Technology Austria.","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>.","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>"},"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"}],"author":[{"id":"2C023F40-F248-11E8-B48F-1D18A9856A87","first_name":"Magdalena","orcid":"0000-0003-1229-9719","last_name":"Steinrück","full_name":"Steinrück, Magdalena"}],"date_updated":"2023-09-07T12:48:43Z","publist_id":"8029","oa":1,"article_processing_charge":"No","_id":"26","publication_identifier":{"issn":["2663-337X"]},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa_version":"Published Version","month":"10","date_published":"2018-10-30T00:00:00Z","publisher":"Institute of Science and Technology Austria","language":[{"iso":"eng"}],"has_accepted_license":"1","degree_awarded":"PhD","department":[{"_id":"CaGu"}],"date_created":"2018-12-11T11:44:14Z","file":[{"file_id":"5941","creator":"dernst","relation":"source_file","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","access_level":"closed","date_updated":"2020-07-14T12:45:43Z","embargo_to":"open_access","checksum":"413cbce1cd1debeae3abe2a25dbc70d1","date_created":"2019-02-08T10:51:22Z","file_size":9190845,"file_name":"Thesis_Steinrueck_final.docx"},{"creator":"dernst","file_id":"5942","relation":"main_file","content_type":"application/pdf","access_level":"open_access","date_updated":"2021-02-11T11:17:14Z","checksum":"3def8b7854c8b42d643597ce0215efac","date_created":"2019-02-08T10:51:22Z","embargo":"2019-11-02","file_size":7521973,"file_name":"Thesis_Steinrueck_final.pdf"}],"day":"30","type":"dissertation","status":"public","supervisor":[{"last_name":"Guet","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"}],"file_date_updated":"2021-02-11T11:17:14Z","page":"109"},{"article_processing_charge":"No","oa":1,"publist_id":"7711","date_updated":"2023-09-15T12:04:56Z","project":[{"grant_number":"24210","name":"Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level (DOC Fellowship)","_id":"251D65D8-B435-11E9-9278-68D0E5697425"}],"oa_version":"Published Version","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","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","publication_identifier":{"issn":["2663-337X"]},"_id":"202","citation":{"ieee":"M. Pleska, “Biology of restriction-modification systems at the single-cell and population level,” Institute of Science and Technology Austria, 2017.","apa":"Pleska, M. (2017). <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>","chicago":"Pleska, Maros. “Biology of Restriction-Modification Systems at the Single-Cell and Population Level.” Institute of Science and Technology Austria, 2017. <a href=\"https://doi.org/10.15479/AT:ISTA:th_916\">https://doi.org/10.15479/AT:ISTA:th_916</a>.","ama":"Pleska M. Biology of restriction-modification systems at the single-cell and population level. 2017. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:th_916\">10.15479/AT:ISTA:th_916</a>","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>.","ista":"Pleska M. 2017. Biology of restriction-modification systems at the single-cell and population level. Institute of Science and Technology Austria.","short":"M. Pleska, Biology of Restriction-Modification Systems at the Single-Cell and Population Level, Institute of Science and Technology Austria, 2017."},"publication_status":"published","author":[{"id":"4569785E-F248-11E8-B48F-1D18A9856A87","first_name":"Maros","full_name":"Pleska, Maros","last_name":"Pleska","orcid":"0000-0001-7460-7479"}],"abstract":[{"lang":"eng","text":"Restriction-modification (RM) represents the simplest and possibly the most widespread mechanism of self/non-self discrimination in nature. In order to provide bacteria with immunity against bacteriophages and other parasitic genetic elements, RM systems rely on a balance between two enzymes: the restriction enzyme, which cleaves non-self DNA at specific restriction sites, and the modification enzyme, which tags the host’s DNA as self and thus protects it from cleavage. In this thesis, I use population and single-cell level experiments in combination with mathematical modeling to study different aspects of the interplay between RM systems, bacteria and bacteriophages. First, I analyze how mutations in phage restriction sites affect the probability of phage escape – an inherently stochastic process, during which phages accidently get modified instead of restricted. Next, I use single-cell experiments to show that RM systems can, with a low probability, attack the genome of their bacterial host and that this primitive form of autoimmunity leads to a tradeoff between the evolutionary cost and benefit of RM systems. Finally, I investigate the nature of interactions between bacteria, RM systems and temperate bacteriophages to find that, as a consequence of phage escape and its impact on population dynamics, RM systems can promote acquisition of symbiotic bacteriophages, rather than limit it. The results presented here uncover new fundamental biological properties of RM systems and highlight their importance in the ecology and evolution of bacteria, bacteriophages and their interactions."}],"tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"alternative_title":["ISTA Thesis"],"ddc":["576","579"],"related_material":{"record":[{"relation":"part_of_dissertation","id":"1243","status":"public"},{"status":"public","relation":"part_of_dissertation","id":"561"},{"id":"457","relation":"part_of_dissertation","status":"public"}]},"year":"2017","doi":"10.15479/AT:ISTA:th_916","title":"Biology of restriction-modification systems at the single-cell and population level","pubrep_id":"916","page":"126","file_date_updated":"2020-07-14T12:45:24Z","type":"dissertation","day":"01","supervisor":[{"first_name":"Calin C","last_name":"Guet","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"}],"status":"public","department":[{"_id":"CaGu"}],"has_accepted_license":"1","degree_awarded":"PhD","file":[{"access_level":"open_access","date_updated":"2020-07-14T12:45:24Z","checksum":"33cfb59674e91f82e3738396d3fb3776","date_created":"2018-12-12T10:08:48Z","file_size":18569590,"file_name":"IST-2018-916-v1+3_2017_Pleska_Maros_Thesis.pdf","creator":"system","file_id":"4710","relation":"main_file","content_type":"application/pdf"},{"file_id":"6204","creator":"dernst","relation":"source_file","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","checksum":"dcc239968decb233e7f98cf1083d8c26","date_created":"2019-04-05T08:33:14Z","file_size":2801649,"file_name":"2017_Pleska_Maros_Thesis.docx","access_level":"closed","date_updated":"2020-07-14T12:45:24Z"}],"date_created":"2018-12-11T11:45:10Z","date_published":"2017-10-01T00:00:00Z","month":"10","language":[{"iso":"eng"}],"publisher":"Institute of Science and Technology Austria"}]