{"oa_version":"Published Version","oa":1,"publication_status":"published","degree_awarded":"PhD","acknowledgement":"For the duration of his PhD, Rok was a recipient of a DOC fellowship of the Austrian Academy of Sciences.","file":[{"access_level":"open_access","file_size":16638998,"date_updated":"2020-07-27T12:00:07Z","creator":"rgrah","file_id":"8176","relation":"main_file","file_name":"Thesis_RokGrah_200727_convertedNew.pdf","success":1,"content_type":"application/pdf","date_created":"2020-07-27T12:00:07Z"},{"access_level":"closed","file_size":347459978,"file_id":"8177","file_name":"Thesis_new.zip","relation":"main_file","content_type":"application/zip","date_created":"2020-07-27T12:02:23Z","date_updated":"2020-07-30T13:04:55Z","creator":"rgrah"}],"has_accepted_license":"1","supervisor":[{"orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gašper","full_name":"Tkačik, Gašper","last_name":"Tkačik","orcid":"0000-0002-6699-1455"}],"date_created":"2020-07-23T09:51:28Z","page":"310","month":"07","date_updated":"2023-09-07T13:13:27Z","_id":"8155","title":"Gene regulation across scales – how biophysical constraints shape evolution","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"author":[{"first_name":"Rok","id":"483E70DE-F248-11E8-B48F-1D18A9856A87","last_name":"Grah","full_name":"Grah, Rok","orcid":"0000-0003-2539-3560"}],"ddc":["530","570"],"type":"dissertation","year":"2020","citation":{"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>.","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>","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>","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.","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>."},"doi":"10.15479/AT:ISTA:8155","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","file_date_updated":"2020-07-30T13:04:55Z","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. "}],"publisher":"Institute of Science and Technology Austria","related_material":{"record":[{"status":"public","id":"7675","relation":"part_of_dissertation"},{"status":"public","id":"7569","relation":"part_of_dissertation"},{"relation":"part_of_dissertation","id":"7652","status":"public"}]},"article_processing_charge":"No","language":[{"iso":"eng"}],"alternative_title":["ISTA Thesis"],"date_published":"2020-07-24T00:00:00Z","publication_identifier":{"issn":["2663-337X"]},"project":[{"name":"Biophysically realistic genotype-phenotype maps for regulatory networks","_id":"267C84F4-B435-11E9-9278-68D0E5697425"}],"day":"24","status":"public"}