[{"article_processing_charge":"No","author":[{"first_name":"Kathrin","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","full_name":"Tomasek, Kathrin","orcid":"0000-0003-3768-877X","last_name":"Tomasek"}],"title":"Pathogenic Escherichia coli hijack the host immune response","citation":{"mla":"Tomasek, Kathrin. Pathogenic Escherichia Coli Hijack the Host Immune Response. Institute of Science and Technology Austria, 2021, doi:10.15479/at:ista:10307.","ieee":"K. Tomasek, “Pathogenic Escherichia coli hijack the host immune response,” Institute of Science and Technology Austria, 2021.","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:10.15479/at:ista:10307","apa":"Tomasek, K. (2021). Pathogenic Escherichia coli hijack the host immune response. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:10307","chicago":"Tomasek, Kathrin. “Pathogenic Escherichia Coli Hijack the Host Immune Response.” Institute of Science and Technology Austria, 2021. https://doi.org/10.15479/at:ista:10307.","ista":"Tomasek K. 2021. Pathogenic Escherichia coli hijack the host immune response. Institute of Science and Technology Austria."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","page":"73","date_created":"2021-11-18T15:05:06Z","doi":"10.15479/at:ista:10307","date_published":"2021-11-18T00:00:00Z","year":"2021","has_accepted_license":"1","day":"18","oa":1,"publisher":"Institute of Science and Technology Austria","file_date_updated":"2022-12-20T23:30:05Z","department":[{"_id":"MiSi"},{"_id":"CaGu"},{"_id":"GradSch"}],"date_updated":"2023-09-07T13:34:38Z","supervisor":[{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","orcid":"0000-0002-4561-241X","full_name":"Sixt, Michael K","last_name":"Sixt"},{"last_name":"Guet","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"}],"ddc":["570"],"type":"dissertation","status":"public","_id":"10307","related_material":{"record":[{"status":"public","id":"10316","relation":"part_of_dissertation"}]},"publication_status":"published","degree_awarded":"PhD","publication_identifier":{"issn":["2663-337X"]},"language":[{"iso":"eng"}],"file":[{"content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"b39c9e0ef18d0484d537a67551effd02","file_id":"10308","embargo":"2022-11-18","date_updated":"2022-12-20T23:30:05Z","file_size":13266088,"creator":"ktomasek","date_created":"2021-11-18T15:07:31Z","file_name":"ThesisTomasekKathrin.pdf"},{"date_created":"2021-11-18T15:07:46Z","file_name":"ThesisTomasekKathrin.docx","date_updated":"2022-12-20T23:30:05Z","file_size":7539509,"creator":"ktomasek","file_id":"10309","checksum":"c0c440ee9e5ef1102a518a4f9f023e7c","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","embargo_to":"open_access","access_level":"closed","relation":"source_file"}],"alternative_title":["ISTA Thesis"],"month":"11","abstract":[{"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.","lang":"eng"}],"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"oa_version":"Published Version"},{"_id":"10316","type":"preprint","status":"public","project":[{"call_identifier":"H2020","_id":"25FE9508-B435-11E9-9278-68D0E5697425","grant_number":"724373","name":"Cellular navigation along spatial gradients"},{"grant_number":"P29911","name":"Mechanical adaptation of lamellipodial actin","_id":"26018E70-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"citation":{"chicago":"Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch, Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2021.10.18.464770.","ista":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. bioRxiv, 10.1101/2021.10.18.464770.","mla":"Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2021.10.18.464770.","ieee":"K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M. K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14,” bioRxiv. Cold Spring Harbor Laboratory.","short":"K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt, BioRxiv (n.d.).","ama":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. bioRxiv. doi:10.1101/2021.10.18.464770","apa":"Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., & Sixt, M. K. (n.d.). Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2021.10.18.464770"},"date_updated":"2024-03-27T23:30:35Z","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","author":[{"id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","first_name":"Kathrin","last_name":"Tomasek","full_name":"Tomasek, Kathrin","orcid":"0000-0003-3768-877X"},{"last_name":"Leithner","full_name":"Leithner, Alexander F","orcid":"0000-0002-1073-744X","first_name":"Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Glatzová","full_name":"Glatzová, Ivana","first_name":"Ivana","id":"727b3c7d-4939-11ec-89b3-b9b0750ab74d"},{"first_name":"Michael S.","last_name":"Lukesch","full_name":"Lukesch, Michael S."},{"orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C"},{"first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","orcid":"0000-0002-4561-241X","full_name":"Sixt, Michael K"}],"article_processing_charge":"No","title":"Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14","department":[{"_id":"CaGu"},{"_id":"MiSi"}],"abstract":[{"lang":"eng","text":"A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on dendritic cells as a previously undescribed binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of pathogenic bacteria to CD14 lead to reduced dendritic cell migration and blunted expression of co-stimulatory molecules, both rate-limiting factors of T cell activation. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease."}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"oa_version":"Preprint","acknowledgement":"We thank Ulrich Dobrindt for providing UPEC strain CFT073, Vlad Gavra and Maximilian Götz, Bor Kavčič, Jonna Alanko and Eva Kiermaier for help with experiments and Robert Hauschild, Julian Stopp and Saren Tasciyan for help with data analysis. We thank the IST Austria Scientific Service Units, especially the Bioimaging facility, the Preclinical facility and the Electron microscopy facility for technical support, Jakob Wallner and all members of the Guet and Sixt lab for fruitful discussions and Daria Siekhaus for critically reading the manuscript. This work was supported by grants from the Austrian Research Promotion Agency (FEMtech 868984) to I.G., the European Research Council (CoG 724373) and the Austrian Science Fund (FWF P29911) to M.S.","publisher":"Cold Spring Harbor Laboratory","main_file_link":[{"url":"https://www.biorxiv.org/content/10.1101/2021.10.18.464770v1","open_access":"1"}],"oa":1,"month":"10","publication_status":"submitted","year":"2021","day":"18","language":[{"iso":"eng"}],"publication":"bioRxiv","doi":"10.1101/2021.10.18.464770","related_material":{"record":[{"id":"11843","status":"public","relation":"later_version"},{"id":"10307","status":"public","relation":"dissertation_contains"}]},"date_published":"2021-10-18T00:00:00Z","date_created":"2021-11-19T12:24:16Z","ec_funded":1},{"date_created":"2020-07-26T22:01:03Z","volume":2173,"doi":"10.1007/978-1-0716-0755-8_16","date_published":"2020-07-11T00:00:00Z","page":"233-246","language":[{"iso":"eng"}],"publication":"Photoswitching Proteins","day":"11","year":"2020","publication_status":"published","publication_identifier":{"eissn":["19406029"],"eisbn":["9781071607558"]},"intvolume":" 2173","month":"07","publisher":"Springer Nature","scopus_import":"1","alternative_title":["Methods in Molecular Biology"],"oa_version":"None","abstract":[{"text":"Understanding how the activity of membrane receptors and cellular signaling pathways shapes cell behavior is of fundamental interest in basic and applied research. Reengineering receptors to react to light instead of their cognate ligands allows for generating defined signaling inputs with high spatial and temporal precision and facilitates the dissection of complex signaling networks. Here, we describe fundamental considerations in the design of light-regulated receptor tyrosine kinases (Opto-RTKs) and appropriate control experiments. We also introduce methods for transient receptor expression in HEK293 cells, quantitative assessment of signaling activity in reporter gene assays, semiquantitative assessment of (in)activation time courses through Western blot (WB) analysis, and easy to implement light stimulation hardware.","lang":"eng"}],"title":"Design and application of light-regulated receptor tyrosine kinases","editor":[{"last_name":"Niopek","full_name":"Niopek, Dominik","first_name":"Dominik"}],"department":[{"_id":"CaGu"}],"article_processing_charge":"No","author":[{"first_name":"Stephanie","id":"32CFBA64-F248-11E8-B48F-1D18A9856A87","last_name":"Kainrath","full_name":"Kainrath, Stephanie"},{"full_name":"Janovjak, Harald L","orcid":"0000-0002-8023-9315","last_name":"Janovjak","first_name":"Harald L","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_updated":"2021-01-12T08:17:17Z","citation":{"ista":"Kainrath S, Janovjak HL. 2020.Design and application of light-regulated receptor tyrosine kinases. In: Photoswitching Proteins. Methods in Molecular Biology, vol. 2173, 233–246.","chicago":"Kainrath, Stephanie, and Harald L Janovjak. “Design and Application of Light-Regulated Receptor Tyrosine Kinases.” In Photoswitching Proteins, edited by Dominik Niopek, 2173:233–46. MIMB. Springer Nature, 2020. https://doi.org/10.1007/978-1-0716-0755-8_16.","ama":"Kainrath S, Janovjak HL. Design and application of light-regulated receptor tyrosine kinases. In: Niopek D, ed. Photoswitching Proteins. Vol 2173. MIMB. Springer Nature; 2020:233-246. doi:10.1007/978-1-0716-0755-8_16","apa":"Kainrath, S., & Janovjak, H. L. (2020). Design and application of light-regulated receptor tyrosine kinases. In D. Niopek (Ed.), Photoswitching Proteins (Vol. 2173, pp. 233–246). Springer Nature. https://doi.org/10.1007/978-1-0716-0755-8_16","ieee":"S. Kainrath and H. L. Janovjak, “Design and application of light-regulated receptor tyrosine kinases,” in Photoswitching Proteins, vol. 2173, D. Niopek, Ed. Springer Nature, 2020, pp. 233–246.","short":"S. Kainrath, H.L. Janovjak, in:, D. Niopek (Ed.), Photoswitching Proteins, Springer Nature, 2020, pp. 233–246.","mla":"Kainrath, Stephanie, and Harald L. Janovjak. “Design and Application of Light-Regulated Receptor Tyrosine Kinases.” Photoswitching Proteins, edited by Dominik Niopek, vol. 2173, Springer Nature, 2020, pp. 233–46, doi:10.1007/978-1-0716-0755-8_16."},"status":"public","type":"book_chapter","series_title":"MIMB","_id":"8173"},{"department":[{"_id":"CaGu"},{"_id":"GaTk"}],"file_date_updated":"2020-07-30T13:04:55Z","supervisor":[{"full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","last_name":"Guet","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper","last_name":"Tkačik","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gašper"}],"date_updated":"2023-09-07T13:13:27Z","ddc":["530","570"],"type":"dissertation","status":"public","_id":"8155","related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"7675"},{"status":"public","id":"7569","relation":"part_of_dissertation"},{"status":"public","id":"7652","relation":"part_of_dissertation"}]},"publication_identifier":{"issn":["2663-337X"]},"publication_status":"published","degree_awarded":"PhD","file":[{"date_created":"2020-07-27T12:00:07Z","file_name":"Thesis_RokGrah_200727_convertedNew.pdf","date_updated":"2020-07-27T12:00:07Z","file_size":16638998,"creator":"rgrah","file_id":"8176","success":1,"content_type":"application/pdf","access_level":"open_access","relation":"main_file"},{"relation":"main_file","access_level":"closed","content_type":"application/zip","file_id":"8177","creator":"rgrah","file_size":347459978,"date_updated":"2020-07-30T13:04:55Z","file_name":"Thesis_new.zip","date_created":"2020-07-27T12:02:23Z"}],"language":[{"iso":"eng"}],"alternative_title":["ISTA Thesis"],"month":"07","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. "}],"oa_version":"Published Version","author":[{"last_name":"Grah","orcid":"0000-0003-2539-3560","full_name":"Grah, Rok","id":"483E70DE-F248-11E8-B48F-1D18A9856A87","first_name":"Rok"}],"article_processing_charge":"No","title":"Gene regulation across scales – how biophysical constraints shape evolution","citation":{"mla":"Grah, Rok. Gene Regulation across Scales – How Biophysical Constraints Shape Evolution. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8155.","ama":"Grah R. Gene regulation across scales – how biophysical constraints shape evolution. 2020. doi:10.15479/AT:ISTA:8155","apa":"Grah, R. (2020). Gene regulation across scales – how biophysical constraints shape evolution. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8155","ieee":"R. Grah, “Gene regulation across scales – how biophysical constraints shape evolution,” Institute of Science and Technology Austria, 2020.","short":"R. Grah, Gene Regulation across Scales – How Biophysical Constraints Shape Evolution, Institute of Science and Technology Austria, 2020.","chicago":"Grah, Rok. “Gene Regulation across Scales – How Biophysical Constraints Shape Evolution.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8155.","ista":"Grah R. 2020. Gene regulation across scales – how biophysical constraints shape evolution. Institute of Science and Technology Austria."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","project":[{"_id":"267C84F4-B435-11E9-9278-68D0E5697425","name":"Biophysically realistic genotype-phenotype maps for regulatory networks"}],"page":"310","doi":"10.15479/AT:ISTA:8155","date_published":"2020-07-24T00:00:00Z","date_created":"2020-07-23T09:51:28Z","has_accepted_license":"1","year":"2020","day":"24","publisher":"Institute of Science and Technology Austria","oa":1,"acknowledgement":"For the duration of his PhD, Rok was a recipient of a DOC fellowship of the Austrian Academy of Sciences."},{"abstract":[{"lang":"eng","text":"In prokaryotes, thermodynamic models of gene regulation provide a highly quantitative mapping from promoter sequences to gene expression levels that is compatible with in vivo and in vitro bio-physical measurements. Such concordance has not been achieved for models of enhancer function in eukaryotes. In equilibrium models, it is difficult to reconcile the reported short transcription factor (TF) residence times on the DNA with the high specificity of regulation. In non-equilibrium models, progress is difficult due to an explosion in the number of parameters. Here, we navigate this complexity by looking for minimal non-equilibrium enhancer models that yield desired regulatory phenotypes: low TF residence time, high specificity and tunable cooperativity. We find that a single extra parameter, interpretable as the “linking rate” by which bound TFs interact with Mediator components, enables our models to escape equilibrium bounds and access optimal regulatory phenotypes, while remaining consistent with the reported phenomenology and simple enough to be inferred from upcoming experiments. We further find that high specificity in non-equilibrium models is in a tradeoff with gene expression noise, predicting bursty dynamics — an experimentally-observed hallmark of eukaryotic transcription. By drastically reducing the vast parameter space to a much smaller subspace that optimally realizes biological function prior to inference from data, our normative approach holds promise for mathematical models in systems biology."}],"oa_version":"Preprint","main_file_link":[{"url":"https://doi.org/10.1101/2020.04.08.029405 ","open_access":"1"}],"oa":1,"publisher":"Cold Spring Harbor Laboratory","month":"04","year":"2020","publication_status":"published","language":[{"iso":"eng"}],"publication":"bioRxiv","day":"09","date_created":"2020-04-23T10:12:51Z","related_material":{"record":[{"id":"8155","status":"public","relation":"dissertation_contains"}]},"date_published":"2020-04-09T00:00:00Z","doi":"10.1101/2020.04.08.029405","_id":"7675","type":"preprint","status":"public","project":[{"_id":"2665AAFE-B435-11E9-9278-68D0E5697425","name":"Can evolution minimize spurious signaling crosstalk to reach optimal performance?","grant_number":"RGP0034/2018"},{"name":"Biophysically realistic genotype-phenotype maps for regulatory networks","_id":"267C84F4-B435-11E9-9278-68D0E5697425"}],"date_updated":"2023-09-07T13:13:26Z","citation":{"apa":"Grah, R., Zoller, B., & Tkačik, G. (2020). Normative models of enhancer function. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.04.08.029405","ama":"Grah R, Zoller B, Tkačik G. Normative models of enhancer function. bioRxiv. 2020. doi:10.1101/2020.04.08.029405","short":"R. Grah, B. Zoller, G. Tkačik, BioRxiv (2020).","ieee":"R. Grah, B. Zoller, and G. Tkačik, “Normative models of enhancer function,” bioRxiv. Cold Spring Harbor Laboratory, 2020.","mla":"Grah, Rok, et al. “Normative Models of Enhancer Function.” BioRxiv, Cold Spring Harbor Laboratory, 2020, doi:10.1101/2020.04.08.029405.","ista":"Grah R, Zoller B, Tkačik G. 2020. Normative models of enhancer function. bioRxiv, 10.1101/2020.04.08.029405.","chicago":"Grah, Rok, Benjamin Zoller, and Gašper Tkačik. “Normative Models of Enhancer Function.” BioRxiv. Cold Spring Harbor Laboratory, 2020. https://doi.org/10.1101/2020.04.08.029405."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_processing_charge":"No","author":[{"first_name":"Rok","id":"483E70DE-F248-11E8-B48F-1D18A9856A87","full_name":"Grah, Rok","orcid":"0000-0003-2539-3560","last_name":"Grah"},{"full_name":"Zoller, Benjamin","last_name":"Zoller","first_name":"Benjamin"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gašper","orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper","last_name":"Tkačik"}],"title":"Normative models of enhancer function","department":[{"_id":"CaGu"},{"_id":"GaTk"}]}]