[{"status":"public","month":"05","date_created":"2019-05-03T11:55:51Z","degree_awarded":"PhD","publisher":"Institute of Science and Technology Austria","file_date_updated":"2021-02-11T11:17:13Z","abstract":[{"lang":"eng","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"}],"publication_status":"published","project":[{"grant_number":"24573","name":"Design principles underlying genetic switch architecture (DOC Fellowship)","_id":"251EE76E-B435-11E9-9278-68D0E5697425"}],"_id":"6371","oa":1,"related_material":{"record":[{"id":"67","relation":"part_of_dissertation","status":"public"},{"id":"5585","status":"public","relation":"popular_science"}]},"ddc":["576","579"],"title":"On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation","year":"2019","author":[{"first_name":"Claudia","last_name":"Igler","full_name":"Igler, Claudia","id":"46613666-F248-11E8-B48F-1D18A9856A87"}],"citation":{"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>","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>.","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.","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>.","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.","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>","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."},"publication_identifier":{"issn":["2663-337X"]},"alternative_title":["ISTA Thesis"],"page":"152","file":[{"embargo":"2020-05-02","content_type":"application/pdf","creator":"cigler","file_size":12597663,"date_created":"2019-05-03T11:54:52Z","relation":"main_file","access_level":"open_access","file_name":"IglerClaudia_OntheNatureofGeneRegulatoryDesign.pdf","checksum":"c0085d47c58c9cbcab1b0a783480f6da","file_id":"6373","date_updated":"2021-02-11T11:17:13Z"},{"date_created":"2019-05-03T11:54:54Z","relation":"source_file","embargo_to":"open_access","file_size":34644426,"creator":"cigler","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_id":"6374","date_updated":"2020-07-14T12:47:28Z","access_level":"closed","checksum":"2eac954de1c8bbf7e6fb35ed0221ae8c","file_name":"IglerClaudia_OntheNatureofGeneRegulatoryDesign.docx"}],"keyword":["gene regulation","biophysics","transcription factor binding","bacteria"],"date_published":"2019-05-03T00:00:00Z","department":[{"_id":"CaGu"}],"has_accepted_license":"1","doi":"10.15479/AT:ISTA:6371","language":[{"iso":"eng"}],"supervisor":[{"last_name":"Guet","first_name":"Calin C","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"}],"day":"03","oa_version":"Published Version","date_updated":"2024-02-21T13:45:52Z","type":"dissertation","article_processing_charge":"No","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1"}]