--- _id: '10307' 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. acknowledged_ssus: - _id: LifeSc - _id: Bio - _id: PreCl - _id: EM-Fac alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Kathrin full_name: Tomasek, Kathrin id: 3AEC8556-F248-11E8-B48F-1D18A9856A87 last_name: Tomasek orcid: 0000-0003-3768-877X citation: 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. ieee: K. Tomasek, “Pathogenic Escherichia coli hijack the host immune response,” Institute of Science and Technology Austria, 2021. ista: Tomasek K. 2021. Pathogenic Escherichia coli hijack the host immune response. Institute of Science and Technology Austria. mla: Tomasek, Kathrin. Pathogenic Escherichia Coli Hijack the Host Immune Response. Institute of Science and Technology Austria, 2021, doi:10.15479/at:ista:10307. short: K. Tomasek, Pathogenic Escherichia Coli Hijack the Host Immune Response, Institute of Science and Technology Austria, 2021. date_created: 2021-11-18T15:05:06Z date_published: 2021-11-18T00:00:00Z date_updated: 2023-09-07T13:34:38Z day: '18' ddc: - '570' degree_awarded: PhD department: - _id: MiSi - _id: CaGu - _id: GradSch doi: 10.15479/at:ista:10307 file: - access_level: open_access checksum: b39c9e0ef18d0484d537a67551effd02 content_type: application/pdf creator: ktomasek date_created: 2021-11-18T15:07:31Z date_updated: 2022-12-20T23:30:05Z embargo: 2022-11-18 file_id: '10308' file_name: ThesisTomasekKathrin.pdf file_size: 13266088 relation: main_file - access_level: closed checksum: c0c440ee9e5ef1102a518a4f9f023e7c content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: ktomasek date_created: 2021-11-18T15:07:46Z date_updated: 2022-12-20T23:30:05Z embargo_to: open_access file_id: '10309' file_name: ThesisTomasekKathrin.docx file_size: 7539509 relation: source_file file_date_updated: 2022-12-20T23:30:05Z has_accepted_license: '1' language: - iso: eng month: '11' oa: 1 oa_version: Published Version page: '73' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '10316' relation: part_of_dissertation status: public status: public supervisor: - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-4561-241X - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 title: Pathogenic Escherichia coli hijack the host immune response type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2021' ... --- _id: '10316' 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 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. article_processing_charge: No author: - first_name: Kathrin full_name: Tomasek, Kathrin id: 3AEC8556-F248-11E8-B48F-1D18A9856A87 last_name: Tomasek orcid: 0000-0003-3768-877X - first_name: Alexander F full_name: Leithner, Alexander F id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87 last_name: Leithner orcid: 0000-0002-1073-744X - first_name: Ivana full_name: Glatzová, Ivana id: 727b3c7d-4939-11ec-89b3-b9b0750ab74d last_name: Glatzová - first_name: Michael S. full_name: Lukesch, Michael S. last_name: Lukesch - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-4561-241X citation: 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 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. 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. 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. short: K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt, BioRxiv (n.d.). date_created: 2021-11-19T12:24:16Z date_published: 2021-10-18T00:00:00Z date_updated: 2024-03-28T23:30:35Z day: '18' department: - _id: CaGu - _id: MiSi doi: 10.1101/2021.10.18.464770 ec_funded: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://www.biorxiv.org/content/10.1101/2021.10.18.464770v1 month: '10' oa: 1 oa_version: Preprint project: - _id: 25FE9508-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '724373' name: Cellular navigation along spatial gradients - _id: 26018E70-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P29911 name: Mechanical adaptation of lamellipodial actin publication: bioRxiv publication_status: submitted publisher: Cold Spring Harbor Laboratory related_material: record: - id: '11843' relation: later_version status: public - id: '10307' relation: dissertation_contains status: public status: public title: Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14 type: preprint user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 year: '2021' ... --- _id: '8173' abstract: - lang: eng 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. alternative_title: - Methods in Molecular Biology article_processing_charge: No author: - first_name: Stephanie full_name: Kainrath, Stephanie id: 32CFBA64-F248-11E8-B48F-1D18A9856A87 last_name: Kainrath - first_name: Harald L full_name: Janovjak, Harald L id: 33BA6C30-F248-11E8-B48F-1D18A9856A87 last_name: Janovjak orcid: 0000-0002-8023-9315 citation: 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 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. 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. 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.' 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. short: S. Kainrath, H.L. Janovjak, in:, D. Niopek (Ed.), Photoswitching Proteins, Springer Nature, 2020, pp. 233–246. date_created: 2020-07-26T22:01:03Z date_published: 2020-07-11T00:00:00Z date_updated: 2021-01-12T08:17:17Z day: '11' department: - _id: CaGu doi: 10.1007/978-1-0716-0755-8_16 editor: - first_name: Dominik full_name: Niopek, Dominik last_name: Niopek intvolume: ' 2173' language: - iso: eng month: '07' oa_version: None page: 233-246 publication: Photoswitching Proteins publication_identifier: eisbn: - '9781071607558' eissn: - '19406029' publication_status: published publisher: Springer Nature scopus_import: '1' series_title: MIMB status: public title: Design and application of light-regulated receptor tyrosine kinases type: book_chapter user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 2173 year: '2020' ... --- _id: '8155' 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. " acknowledgement: For the duration of his PhD, Rok was a recipient of a DOC fellowship of the Austrian Academy of Sciences. alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Rok full_name: Grah, Rok id: 483E70DE-F248-11E8-B48F-1D18A9856A87 last_name: Grah orcid: 0000-0003-2539-3560 citation: 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 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. ieee: 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. Gene Regulation across Scales – How Biophysical Constraints Shape Evolution. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8155. short: R. Grah, Gene Regulation across Scales – How Biophysical Constraints Shape Evolution, Institute of Science and Technology Austria, 2020. date_created: 2020-07-23T09:51:28Z date_published: 2020-07-24T00:00:00Z date_updated: 2023-09-07T13:13:27Z day: '24' ddc: - '530' - '570' degree_awarded: PhD department: - _id: CaGu - _id: GaTk doi: 10.15479/AT:ISTA:8155 file: - access_level: open_access content_type: application/pdf creator: rgrah date_created: 2020-07-27T12:00:07Z date_updated: 2020-07-27T12:00:07Z file_id: '8176' file_name: Thesis_RokGrah_200727_convertedNew.pdf file_size: 16638998 relation: main_file success: 1 - access_level: closed content_type: application/zip creator: rgrah date_created: 2020-07-27T12:02:23Z date_updated: 2020-07-30T13:04:55Z file_id: '8177' file_name: Thesis_new.zip file_size: 347459978 relation: main_file file_date_updated: 2020-07-30T13:04:55Z has_accepted_license: '1' language: - iso: eng month: '07' oa: 1 oa_version: Published Version page: '310' project: - _id: 267C84F4-B435-11E9-9278-68D0E5697425 name: Biophysically realistic genotype-phenotype maps for regulatory networks publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '7675' relation: part_of_dissertation status: public - id: '7569' relation: part_of_dissertation status: public - id: '7652' relation: part_of_dissertation status: public status: public supervisor: - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 title: Gene regulation across scales – how biophysical constraints shape evolution type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2020' ... --- _id: '7675' 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.' article_processing_charge: No author: - first_name: Rok full_name: Grah, Rok id: 483E70DE-F248-11E8-B48F-1D18A9856A87 last_name: Grah orcid: 0000-0003-2539-3560 - first_name: Benjamin full_name: Zoller, Benjamin last_name: Zoller - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 citation: ama: Grah R, Zoller B, Tkačik G. Normative models of enhancer function. bioRxiv. 2020. doi:10.1101/2020.04.08.029405 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 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. ieee: R. Grah, B. Zoller, and G. Tkačik, “Normative models of enhancer function,” bioRxiv. Cold Spring Harbor Laboratory, 2020. ista: Grah R, Zoller B, Tkačik G. 2020. Normative models of enhancer function. bioRxiv, 10.1101/2020.04.08.029405. mla: Grah, Rok, et al. “Normative Models of Enhancer Function.” BioRxiv, Cold Spring Harbor Laboratory, 2020, doi:10.1101/2020.04.08.029405. short: R. Grah, B. Zoller, G. Tkačik, BioRxiv (2020). date_created: 2020-04-23T10:12:51Z date_published: 2020-04-09T00:00:00Z date_updated: 2023-09-07T13:13:26Z day: '09' department: - _id: CaGu - _id: GaTk doi: 10.1101/2020.04.08.029405 language: - iso: eng main_file_link: - open_access: '1' url: 'https://doi.org/10.1101/2020.04.08.029405 ' month: '04' oa: 1 oa_version: Preprint project: - _id: 2665AAFE-B435-11E9-9278-68D0E5697425 grant_number: RGP0034/2018 name: Can evolution minimize spurious signaling crosstalk to reach optimal performance? - _id: 267C84F4-B435-11E9-9278-68D0E5697425 name: Biophysically realistic genotype-phenotype maps for regulatory networks publication: bioRxiv publication_status: published publisher: Cold Spring Harbor Laboratory related_material: record: - id: '8155' relation: dissertation_contains status: public status: public title: Normative models of enhancer function type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2020' ...