[{"file_date_updated":"2021-02-11T11:17:13Z","page":"152","status":"public","supervisor":[{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","last_name":"Guet","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052"}],"day":"03","type":"dissertation","date_created":"2019-05-03T11:55:51Z","file":[{"content_type":"application/pdf","relation":"main_file","file_id":"6373","creator":"cigler","date_updated":"2021-02-11T11:17:13Z","access_level":"open_access","file_name":"IglerClaudia_OntheNatureofGeneRegulatoryDesign.pdf","embargo":"2020-05-02","file_size":12597663,"date_created":"2019-05-03T11:54:52Z","checksum":"c0085d47c58c9cbcab1b0a783480f6da"},{"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","relation":"source_file","creator":"cigler","file_id":"6374","embargo_to":"open_access","date_updated":"2020-07-14T12:47:28Z","access_level":"closed","file_name":"IglerClaudia_OntheNatureofGeneRegulatoryDesign.docx","file_size":34644426,"date_created":"2019-05-03T11:54:54Z","checksum":"2eac954de1c8bbf7e6fb35ed0221ae8c"}],"has_accepted_license":"1","degree_awarded":"PhD","department":[{"_id":"CaGu"}],"publisher":"Institute of Science and Technology Austria","language":[{"iso":"eng"}],"month":"05","date_published":"2019-05-03T00:00:00Z","_id":"6371","publication_identifier":{"issn":["2663-337X"]},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa_version":"Published Version","project":[{"name":"Design principles underlying genetic switch architecture (DOC Fellowship)","_id":"251EE76E-B435-11E9-9278-68D0E5697425","grant_number":"24573"}],"date_updated":"2024-02-21T13:45:52Z","oa":1,"article_processing_charge":"No","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"}],"author":[{"last_name":"Igler","full_name":"Igler, Claudia","first_name":"Claudia","id":"46613666-F248-11E8-B48F-1D18A9856A87"}],"keyword":["gene regulation","biophysics","transcription factor binding","bacteria"],"publication_status":"published","citation":{"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.","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>.","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>","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>.","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>","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."},"related_material":{"record":[{"relation":"part_of_dissertation","id":"67","status":"public"},{"status":"public","id":"5585","relation":"popular_science"}]},"ddc":["576","579"],"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":["570"],"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)"},"article_number":"e3018","title":"Platelet migration and bacterial trapping assay under flow","doi":"10.21769/bioprotoc.3018","year":"2018","ec_funded":1,"publication_identifier":{"issn":["2331-8325"]},"_id":"6354","quality_controlled":"1","project":[{"grant_number":"747687","call_identifier":"H2020","_id":"260AA4E2-B435-11E9-9278-68D0E5697425","name":"Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells"}],"oa_version":"Published Version","acknowledgement":" FöFoLe project 947 (F.G.), the Friedrich-Baur-Stiftung project 41/16 (F.G.)","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","volume":8,"date_updated":"2021-01-12T08:07:12Z","oa":1,"abstract":[{"lang":"eng","text":"Blood platelets are critical for hemostasis and thrombosis, but also play diverse roles during immune responses. We have recently reported that platelets migrate at sites of infection in vitro and in vivo. Importantly, platelets use their ability to migrate to collect and bundle fibrin (ogen)-bound bacteria accomplishing efficient intravascular bacterial trapping. Here, we describe a method that allows analyzing platelet migration in vitro, focusing on their ability to collect bacteria and trap bacteria under flow."}],"author":[{"first_name":"Shuxia","full_name":"Fan, Shuxia","last_name":"Fan"},{"first_name":"Michael","last_name":"Lorenz","full_name":"Lorenz, Michael"},{"full_name":"Massberg, Steffen","last_name":"Massberg","first_name":"Steffen"},{"orcid":"0000-0001-6120-3723","full_name":"Gärtner, Florian R","last_name":"Gärtner","first_name":"Florian R","id":"397A88EE-F248-11E8-B48F-1D18A9856A87"}],"keyword":["Platelets","Cell migration","Bacteria","Shear flow","Fibrinogen","E. coli"],"citation":{"ieee":"S. Fan, M. Lorenz, S. Massberg, and F. R. Gärtner, “Platelet migration and bacterial trapping assay under flow,” <i>Bio-Protocol</i>, vol. 8, no. 18. Bio-Protocol, 2018.","apa":"Fan, S., Lorenz, M., Massberg, S., &#38; Gärtner, F. R. (2018). Platelet migration and bacterial trapping assay under flow. <i>Bio-Protocol</i>. Bio-Protocol. <a href=\"https://doi.org/10.21769/bioprotoc.3018\">https://doi.org/10.21769/bioprotoc.3018</a>","chicago":"Fan, Shuxia, Michael Lorenz, Steffen Massberg, and Florian R Gärtner. “Platelet Migration and Bacterial Trapping Assay under Flow.” <i>Bio-Protocol</i>. Bio-Protocol, 2018. <a href=\"https://doi.org/10.21769/bioprotoc.3018\">https://doi.org/10.21769/bioprotoc.3018</a>.","ama":"Fan S, Lorenz M, Massberg S, Gärtner FR. Platelet migration and bacterial trapping assay under flow. <i>Bio-Protocol</i>. 2018;8(18). doi:<a href=\"https://doi.org/10.21769/bioprotoc.3018\">10.21769/bioprotoc.3018</a>","mla":"Fan, Shuxia, et al. “Platelet Migration and Bacterial Trapping Assay under Flow.” <i>Bio-Protocol</i>, vol. 8, no. 18, e3018, Bio-Protocol, 2018, doi:<a href=\"https://doi.org/10.21769/bioprotoc.3018\">10.21769/bioprotoc.3018</a>.","short":"S. Fan, M. Lorenz, S. Massberg, F.R. Gärtner, Bio-Protocol 8 (2018).","ista":"Fan S, Lorenz M, Massberg S, Gärtner FR. 2018. Platelet migration and bacterial trapping assay under flow. Bio-Protocol. 8(18), e3018."},"publication_status":"published","file":[{"creator":"dernst","file_id":"6360","content_type":"application/pdf","relation":"main_file","date_updated":"2020-07-14T12:47:28Z","access_level":"open_access","date_created":"2019-04-30T08:04:33Z","checksum":"d4588377e789da7f360b553ae02c5119","file_name":"2018_BioProtocol_Fan.pdf","file_size":2928337}],"date_created":"2019-04-29T09:40:33Z","has_accepted_license":"1","department":[{"_id":"MiSi"}],"publisher":"Bio-Protocol","language":[{"iso":"eng"}],"month":"09","date_published":"2018-09-20T00:00:00Z","publication":"Bio-Protocol","issue":"18","file_date_updated":"2020-07-14T12:47:28Z","intvolume":"         8","status":"public","day":"20","type":"journal_article"}]