--- OA_place: publisher _id: '12491' abstract: - lang: eng text: "The extracellular matrix (ECM) is a hydrated and complex three-dimensional network consisting of proteins, polysaccharides, and water. It provides structural scaffolding for the cells embedded within it and is essential in regulating numerous physiological processes, including cell migration and proliferation, wound healing, and stem cell fate. \r\nDespite extensive study, detailed structural knowledge of ECM components in physiologically relevant conditions is still rudimentary. This is due to methodological limitations in specimen preparation protocols which are incompatible with keeping large samples, such as the ECM, in their native state for subsequent imaging. Conventional electron microscopy (EM) techniques rely on fixation, dehydration, contrasting, and sectioning. This results in the alteration of a highly hydrated environment and the potential introduction of artifacts. Other structural biology techniques, such as nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography, allow high-resolution analysis of protein structures but only work on homogenous and purified samples, hence lacking contextual information. Currently, no approach exists for the ultrastructural and structural study of extracellular components under native conditions in a physiological, 3D environment. \r\nIn this thesis, I have developed a workflow that allows for the ultrastructural analysis of the ECM in near-native conditions at molecular resolution. The developments I introduced include implementing a novel specimen preparation workflow for cell-derived matrices (CDMs) to render them compatible with ion-beam milling and subsequent high-resolution cryo-electron tomography (ET). \r\nTo this end, I have established protocols to generate CDMs grown over several weeks on EM grids that are compatible with downstream cryo-EM sample preparation and imaging techniques. Characterization of these ECMs confirmed that they contain essential ECM components such as collagen I, collagen VI, and fibronectin I in high abundance and hence represent a bona fide biologically-relevant sample. I successfully optimized vitrification of these specimens by testing various vitrification techniques and cryoprotectants. \r\nIn order to obtain high-resolution molecular insights into the ultrastructure and organization of CDMs, I established cryo-focused ion beam scanning electron microscopy (FIBSEM) on these challenging and complex specimens. I explored different approaches for the creation of thin cryo-lamellae by FIB milling and succeeded in optimizing the cryo-lift-out technique, resulting in high-quality lamellae of approximately 200 nm thickness. \r\nHigh-resolution Cryo-ET of these lamellae revealed for the first time the architecture of native CDM in the context of matrix-secreting cells. This allowed for the in situ visualization of fibrillar matrix proteins such as collagen, laying the foundation for future structural and ultrastructural characterization of these proteins in their near-native environment. \r\nIn summary, in this thesis, I present a novel workflow that combines state-of-the-art cryo-EM specimen preparation and imaging technologies to permit characterization of the ECM, an important tissue component in higher organisms. This innovative and highly versatile workflow will enable addressing far-reaching questions on ECM architecture, composition, and reciprocal ECM-cell interactions." acknowledged_ssus: - _id: EM-Fac - _id: LifeSc - _id: Bio alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Bettina full_name: Zens, Bettina id: 45FD126C-F248-11E8-B48F-1D18A9856A87 last_name: Zens orcid: 0000-0002-9561-1239 citation: ama: Zens B. Ultrastructural characterization of natively preserved extracellular matrix by cryo-electron tomography. 2023. doi:10.15479/at:ista:12491 apa: Zens, B. (2023). Ultrastructural characterization of natively preserved extracellular matrix by cryo-electron tomography. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12491 chicago: Zens, Bettina. “Ultrastructural Characterization of Natively Preserved Extracellular Matrix by Cryo-Electron Tomography.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:12491. ieee: B. Zens, “Ultrastructural characterization of natively preserved extracellular matrix by cryo-electron tomography,” Institute of Science and Technology Austria, 2023. ista: Zens B. 2023. Ultrastructural characterization of natively preserved extracellular matrix by cryo-electron tomography. Institute of Science and Technology Austria. mla: Zens, Bettina. Ultrastructural Characterization of Natively Preserved Extracellular Matrix by Cryo-Electron Tomography. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:12491. short: B. Zens, Ultrastructural Characterization of Natively Preserved Extracellular Matrix by Cryo-Electron Tomography, Institute of Science and Technology Austria, 2023. corr_author: '1' date_created: 2023-02-02T14:50:20Z date_published: 2023-02-02T00:00:00Z date_updated: 2026-04-07T13:49:23Z day: '02' ddc: - '570' degree_awarded: PhD department: - _id: GradSch - _id: FlSc doi: 10.15479/at:ista:12491 file: - access_level: open_access checksum: 069d87f025e0799bf9e3c375664264f2 content_type: application/pdf creator: bzens date_created: 2023-02-07T13:07:38Z date_updated: 2024-02-08T23:30:04Z embargo: 2024-02-07 file_id: '12527' file_name: PhDThesis_BettinaZens_2023_final.pdf file_size: 23082464 relation: main_file - access_level: closed checksum: 8c66ed203495d6e078ed1002a866520c content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: bzens date_created: 2023-02-07T13:09:05Z date_updated: 2024-02-08T23:30:04Z embargo_to: open_access file_id: '12528' file_name: PhDThesis_BettinaZens_2023_final.docx file_size: 106169509 relation: source_file file_date_updated: 2024-02-08T23:30:04Z has_accepted_license: '1' keyword: - cryo-EM - cryo-ET - FIB milling - method development - FIBSEM - extracellular matrix - ECM - cell-derived matrices - CDMs - cell culture - high pressure freezing - HPF - structural biology - tomography - collagen language: - iso: eng month: '02' oa: 1 oa_version: Published Version page: '187' project: - _id: eba3b5f6-77a9-11ec-83b8-cf0905748aa3 name: Integrated visual proteomics of reciprocal cell-extracellular matrix interactions - _id: 059B463C-7A3F-11EA-A408-12923DDC885E name: "NÃ\x96-Fonds Preis für die Jungforscherin des Jahres am IST Austria" publication_identifier: isbn: - 978-3-99078-027-5 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '8586' relation: part_of_dissertation status: public status: public supervisor: - first_name: Florian KM full_name: Schur, Florian KM id: 48AD8942-F248-11E8-B48F-1D18A9856A87 last_name: Schur orcid: 0000-0003-4790-8078 title: Ultrastructural characterization of natively preserved extracellular matrix by cryo-electron tomography type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2023' ... --- OA_place: publisher _id: '13984' abstract: - lang: eng text: "Social insects fight disease using their individual immune systems and the cooperative\r\nsanitary behaviors of colony members. These social defenses are well explored against\r\nexternally-infecting pathogens, but little is known about defense strategies against\r\ninternally-infecting pathogens, such as viruses. Viruses are ubiquitous and in the last decades\r\nit has become evident that also many ant species harbor viruses. We present one of the first\r\nstudies addressing transmission dynamics and collective disease defenses against viruses in\r\nants on a mechanistic level. I successfully established an experimental ant host – viral\r\npathogen system as a model for the defense strategies used by social insects against internal\r\npathogen infections, as outlined in the third chapter. In particular, we studied how garden ants\r\n(Lasius neglectus) defend themselves and their colonies against the generalist insect virus\r\nCrPV (cricket paralysis virus). We chose microinjections of virus directly into the ants’\r\nhemolymph because it allowed us to use a defined exposure dose. Here we show that this is a\r\ngood model system, as the virus is replicating and thus infecting the host. The ants mount a\r\nclear individual immune response against the viral infection, which is characterized by a\r\nspecific siRNA pattern, namely siRNAs mapping against the viral genome with a peak of 21\r\nand 22 bp long fragments. The onset of this immune response is consistent with the timeline\r\nof viral replication that starts already within two days post injection. The disease manifests in\r\ndecreased survival over a course of two to three weeks.\r\nRegarding group living, we find that infected ants show a strong individual immune response,\r\nbut that their course of disease is little affected by nestmate presence, as described in chapter\r\nfour. Hence, we do not find social immunity in the context of viral infections in ants.\r\nNestmates, however, can contract the virus. Using Drosophila S2R+ cells in culture, we\r\nshowed that 94 % of the nestmates contract active virus within four days of social contact to\r\nan infected individual. Virus is transmitted in low doses, thus not causing disease\r\ntransmission within the colony. While virus can be transmitted during short direct contacts,\r\nwe also assume transmission from deceased ants and show that the nestmates’ immune\r\nsystem gets activated after contracting a low viral dose. We find considerable potential for\r\nindirect transmission via the nest space. Virus is shed to the nest, where it stays viable for one\r\nweek and is also picked up by other ants. Apart from that, we want to underline the potential\r\nof ant poison as antiviral agent. We determined that ant poison successfully inactivates CrPV\r\nin vitro. However, we found no evidence for effective poison use to sanitize the nest space.\r\nOn the other hand, local application of ant poison by oral poison uptake, which is part of the\r\nants prophylactic behavioral repertoire, probably contributes to keeping the gut of each\r\nindividual sanitized. We hypothesize that oral poison uptake might be the reason why we did\r\nnot find viable virus in the trophallactic fluid.\r\nThe fifth chapter encompasses preliminary data on potential social immunization. However,\r\nour experiments do not confirm an actual survival benefit for the nestmates upon pathogen\r\nchallenge under the given experimental settings. Nevertheless, we do not want to rule out the\r\npossibility for nestmate immunization, but rather emphasize that considering different\r\nexperimental timelines and viral doses would provide a multitude of options for follow-up\r\nexperiments.\r\nIn conclusion, we find that prophylactic individual behaviors, such as oral poison uptake,\r\nmight play a role in preventing viral disease transmission. Compared to colony defense\r\nagainst external pathogens, internal pathogen infections require a stronger component of\r\nindividual physiological immunity than behavioral social immunity, yet could still lead to\r\ncollective protection." acknowledged_ssus: - _id: LifeSc alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Anna full_name: Franschitz, Anna id: 480826C8-F248-11E8-B48F-1D18A9856A87 last_name: Franschitz citation: ama: Franschitz A. Individual and social immunity against viral infections in ants. 2023. doi:10.15479/at:ista:13984 apa: Franschitz, A. (2023). Individual and social immunity against viral infections in ants. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:13984 chicago: Franschitz, Anna. “Individual and Social Immunity against Viral Infections in Ants.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:13984. ieee: A. Franschitz, “Individual and social immunity against viral infections in ants,” Institute of Science and Technology Austria, 2023. ista: Franschitz A. 2023. Individual and social immunity against viral infections in ants. Institute of Science and Technology Austria. mla: Franschitz, Anna. Individual and Social Immunity against Viral Infections in Ants. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:13984. short: A. Franschitz, Individual and Social Immunity against Viral Infections in Ants, Institute of Science and Technology Austria, 2023. corr_author: '1' date_created: 2023-08-08T15:33:29Z date_published: 2023-08-08T00:00:00Z date_updated: 2026-04-07T13:51:29Z day: '08' ddc: - '570' - '577' degree_awarded: PhD department: - _id: GradSch - _id: SyCr doi: 10.15479/at:ista:13984 file: - access_level: open_access checksum: 55c876b73d49db15228a7f571592ec77 content_type: application/pdf creator: cchlebak date_created: 2024-03-01T08:56:06Z date_updated: 2024-10-29T23:31:04Z embargo_to: open_access file_id: '15044' file_name: Print_Version_Franschitz_Anna_Thesis.pdf file_size: 10416761 relation: main_file title: Combined Version of original Thesis and Addendum - access_level: open_access checksum: 27220243d5d51c3b0d7d61c0879d7a0c content_type: application/pdf creator: afransch date_created: 2023-08-08T18:01:28Z date_updated: 2024-08-09T22:30:03Z embargo: 2024-08-08 file_id: '13986' file_name: Thesis_AnnaFranschitz_202308.pdf file_size: 10797612 relation: main_file - access_level: closed checksum: 40abf7ccca14a3893f72dc7fb88585d6 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: afransch date_created: 2023-08-08T18:02:25Z date_updated: 2024-08-09T22:30:03Z embargo_to: open_access file_id: '13987' file_name: Thesis_AnnaFranschitz_202308.docx file_size: 2619085 relation: source_file - access_level: open_access checksum: 8b991ecc2d59d045cc3cf0d676785ec7 content_type: application/pdf creator: cchlebak date_created: 2024-03-01T08:37:15Z date_updated: 2024-10-29T23:31:04Z description: Minor modifications and clarifications - Feb 2024 embargo: 2024-08-08 file_id: '15042' file_name: Addendum_AnnaFranschitz202402.pdf file_size: 85956 relation: main_file title: Addendum - access_level: closed checksum: 66745aa01f960f17472c024875c049ed content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: cchlebak date_created: 2024-03-01T08:39:20Z date_updated: 2024-08-09T22:30:03Z embargo_to: open_access file_id: '15043' file_name: Addendum_AnnaFranschitz202402.docx file_size: 11818 relation: source_file title: Addendum - source file file_date_updated: 2024-10-29T23:31:04Z has_accepted_license: '1' language: - iso: eng month: '08' oa: 1 oa_version: Published Version page: '89' publication_identifier: isbn: - 978-3-99078-034-3 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria status: public supervisor: - first_name: Sylvia full_name: Cremer, Sylvia id: 2F64EC8C-F248-11E8-B48F-1D18A9856A87 last_name: Cremer orcid: 0000-0002-2193-3868 title: Individual and social immunity against viral infections in ants type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2023' ... --- OA_place: publisher _id: '12964' abstract: - lang: eng text: "Pattern formation is of great importance for its contribution across different biological behaviours. During developmental processes for example, patterns of chemical gradients are\r\nestablished to determine cell fate and complex tissue patterns emerge to define structures such\r\nas limbs and vascular networks. Patterns are also seen in collectively migrating groups, for\r\ninstance traveling waves of density emerging in moving animal flocks as well as collectively migrating cells and tissues. To what extent these biological patterns arise spontaneously through\r\nthe local interaction of individual constituents or are dictated by higher level instructions is\r\nstill an open question however there is evidence for the involvement of both types of process.\r\nWhere patterns arise spontaneously there is a long standing interest in how far the interplay\r\nof mechanics, e.g. force generation and deformation, and chemistry, e.g. gene regulation\r\nand signaling, contributes to the behaviour. This is because many systems are able to both\r\nchemically regulate mechanical force production and chemically sense mechanical deformation,\r\nforming mechano-chemical feedback loops which can potentially become unstable towards\r\nspatio and/or temporal patterning.\r\nWe work with experimental collaborators to investigate the possibility that this type of\r\ninteraction drives pattern formation in biological systems at different scales. We focus first on\r\ntissue-level ERK-density waves observed during the wound healing response across different\r\nsystems where many previous studies have proposed that patterns depend on polarized cell\r\nmigration and arise from a mechanical flocking-like mechanism. By combining theory with\r\nmechanical and optogenetic perturbation experiments on in vitro monolayers we instead find\r\nevidence for mechanochemical pattern formation involving only scalar bilateral feedbacks\r\nbetween ERK signaling and cell contraction. We perform further modeling and experiment\r\nto study how this instability couples with polar cell migration in order to produce a robust\r\nand efficient wound healing response. In a following chapter we implement ERK-density\r\ncoupling and cell migration in a 2D active vertex model to investigate the interaction of\r\nERK-density patterning with different tissue rheologies and find that the spatio-temporal\r\ndynamics are able to both locally and globally fluidize a tissue across the solid-fluid glass\r\ntransition. In a last chapter we move towards lower spatial scales in the context of subcellular\r\npatterning of the cell cytoskeleton where we investigate the transition between phases of\r\nspatially homogeneous temporal oscillations and chaotic spatio-temporal patterning in the\r\ndynamics of myosin and ROCK activities (a motor component of the actomyosin cytoskeleton\r\nand its activator). Experimental evidence supports an intrinsic chemical oscillator which we\r\nencode in a reaction model and couple to a contractile active gel description of the cell cortex.\r\nThe model exhibits phases of chemical oscillations and contractile spatial patterning which\r\nreproduce many features of the dynamics seen in Drosophila oocyte epithelia in vivo. However,\r\nadditional pharmacological perturbations to inhibit myosin contractility leaves the role of\r\ncontractile instability unclear. We discuss alternative hypotheses and investigate the possibility\r\nof reaction-diffusion instability." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Daniel R full_name: Boocock, Daniel R id: 453AF628-F248-11E8-B48F-1D18A9856A87 last_name: Boocock orcid: 0000-0002-1585-2631 citation: ama: Boocock DR. Mechanochemical pattern formation across biological scales. 2023. doi:10.15479/at:ista:12964 apa: Boocock, D. R. (2023). Mechanochemical pattern formation across biological scales. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12964 chicago: Boocock, Daniel R. “Mechanochemical Pattern Formation across Biological Scales.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:12964. ieee: D. R. Boocock, “Mechanochemical pattern formation across biological scales,” Institute of Science and Technology Austria, 2023. ista: Boocock DR. 2023. Mechanochemical pattern formation across biological scales. Institute of Science and Technology Austria. mla: Boocock, Daniel R. Mechanochemical Pattern Formation across Biological Scales. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:12964. short: D.R. Boocock, Mechanochemical Pattern Formation across Biological Scales, Institute of Science and Technology Austria, 2023. corr_author: '1' date_created: 2023-05-15T14:52:36Z date_published: 2023-05-17T00:00:00Z date_updated: 2026-04-07T13:52:57Z day: '17' ddc: - '530' degree_awarded: PhD department: - _id: GradSch - _id: EdHa doi: 10.15479/at:ista:12964 ec_funded: 1 file: - access_level: open_access checksum: d51240675fc6dc0e3f5dc0c902695d3a content_type: application/pdf creator: dboocock date_created: 2023-05-17T13:39:54Z date_updated: 2024-05-18T22:30:03Z embargo: 2024-05-17 file_id: '12988' file_name: thesis_boocock.pdf file_size: 40414730 relation: main_file - access_level: closed checksum: 581a2313ffeb40fe77e8a122a25a7795 content_type: application/zip creator: dboocock date_created: 2023-05-17T13:39:53Z date_updated: 2024-05-18T22:30:03Z embargo_to: open_access file_id: '12989' file_name: thesis_boocock.zip file_size: 34338567 relation: source_file file_date_updated: 2024-05-18T22:30:03Z has_accepted_license: '1' language: - iso: eng license: https://creativecommons.org/licenses/by-nc-sa/4.0/ month: '05' oa: 1 oa_version: Published Version page: '146' project: - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program publication_identifier: isbn: - 978-3-99078-032-9 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '8602' relation: part_of_dissertation status: public status: public supervisor: - first_name: Edouard B full_name: Hannezo, Edouard B id: 3A9DB764-F248-11E8-B48F-1D18A9856A87 last_name: Hannezo orcid: 0000-0001-6005-1561 title: Mechanochemical pattern formation across biological scales tmp: image: /images/cc_by_nc_sa.png legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) short: CC BY-NC-SA (4.0) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2023' ... --- _id: '12891' abstract: - lang: eng text: "The tight spatiotemporal coordination of signaling activity determining embryo\r\npatterning and the physical processes driving embryo morphogenesis renders\r\nembryonic development robust, such that key developmental processes can unfold\r\nrelatively normally even outside of the full embryonic context. For instance, embryonic\r\nstem cell cultures can recapitulate the hallmarks of gastrulation, i.e. break symmetry\r\nleading to germ layer formation and morphogenesis, in a very reduced environment.\r\nThis leads to questions on specific contributions of embryo-specific features, such as\r\nthe presence of extraembryonic tissues, which are inherently involved in gastrulation\r\nin the full embryonic context. To address this, we established zebrafish embryonic\r\nexplants without the extraembryonic yolk cell, an important player as a signaling\r\nsource and for morphogenesis during gastrulation, as a model of ex vivo development.\r\nWe found that dorsal-marginal determinants are required and sufficient in these\r\nexplants to form and pattern all three germ layers. However, formation of tissues,\r\nwhich require the highest Nodal-signaling levels, is variable, demonstrating a\r\ncontribution of extraembryonic tissues for reaching peak Nodal signaling levels.\r\nBlastoderm explants also undergo gastrulation-like axis elongation. We found that this\r\nelongation movement shows hallmarks of oriented mesendoderm cell intercalations\r\ntypically associated with dorsal tissues in the intact embryo. These are disrupted by\r\nuniform upregulation of BMP signaling activity and concomitant explant ventralization,\r\nsuggesting that tight spatial control of BMP signaling is a prerequisite for explant\r\nmorphogenesis. This control is achieved by Nodal signaling, which is critical for\r\neffectively downregulating BMP signaling in the mesendoderm, highlighting that Nodal\r\nsignaling is not only directly required for mesendoderm cell fate specification and\r\nmorphogenesis, but also by maintaining low levels of BMP signaling at the dorsal side.\r\nCollectively, we provide insights into the capacity and organization of signaling and\r\nmorphogenetic domains to recapitulate features of zebrafish gastrulation outside of\r\nthe full embryonic context." acknowledged_ssus: - _id: Bio - _id: LifeSc alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Alexandra full_name: Schauer, Alexandra id: 30A536BA-F248-11E8-B48F-1D18A9856A87 last_name: Schauer orcid: 0000-0001-7659-9142 citation: ama: 'Schauer A. Mesendoderm formation in zebrafish gastrulation: The role of extraembryonic tissues. 2023. doi:10.15479/at:ista:12891' apa: 'Schauer, A. (2023). Mesendoderm formation in zebrafish gastrulation: The role of extraembryonic tissues. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12891' chicago: 'Schauer, Alexandra. “Mesendoderm Formation in Zebrafish Gastrulation: The Role of Extraembryonic Tissues.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:12891.' ieee: 'A. Schauer, “Mesendoderm formation in zebrafish gastrulation: The role of extraembryonic tissues,” Institute of Science and Technology Austria, 2023.' ista: 'Schauer A. 2023. Mesendoderm formation in zebrafish gastrulation: The role of extraembryonic tissues. Institute of Science and Technology Austria.' mla: 'Schauer, Alexandra. Mesendoderm Formation in Zebrafish Gastrulation: The Role of Extraembryonic Tissues. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:12891.' short: 'A. Schauer, Mesendoderm Formation in Zebrafish Gastrulation: The Role of Extraembryonic Tissues, Institute of Science and Technology Austria, 2023.' corr_author: '1' date_created: 2023-05-05T08:48:20Z date_published: 2023-05-05T00:00:00Z date_updated: 2025-06-12T06:56:58Z day: '05' ddc: - '570' degree_awarded: PhD department: - _id: GradSch - _id: CaHe doi: 10.15479/at:ista:12891 ec_funded: 1 file: - access_level: open_access checksum: 59b0303dc483f40a96a610a90aab7ee9 content_type: application/pdf creator: aschauer date_created: 2023-05-05T13:01:14Z date_updated: 2024-05-06T22:30:03Z embargo: 2024-05-05 file_id: '12907' file_name: Thesis_Schauer_final.pdf file_size: 31434230 relation: main_file - access_level: closed checksum: 25f54e12479b6adaabd129a20568e6c1 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: aschauer date_created: 2023-05-05T13:04:15Z date_updated: 2024-05-06T22:30:03Z embargo_to: open_access file_id: '12908' file_name: Thesis_Schauer_final.docx file_size: 43809109 relation: source_file file_date_updated: 2024-05-06T22:30:03Z has_accepted_license: '1' language: - iso: eng month: '05' oa: 1 oa_version: Published Version page: '190' project: - _id: 260F1432-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '742573' name: Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation - _id: 26B1E39C-B435-11E9-9278-68D0E5697425 grant_number: '25239' name: 'Mesendoderm specification in zebrafish: The role of extraembryonic tissues' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '7888' relation: part_of_dissertation status: public - id: '8966' relation: part_of_dissertation status: public status: public supervisor: - first_name: Carl-Philipp J full_name: Heisenberg, Carl-Philipp J id: 39427864-F248-11E8-B48F-1D18A9856A87 last_name: Heisenberg orcid: 0000-0002-0912-4566 title: 'Mesendoderm formation in zebrafish gastrulation: The role of extraembryonic tissues' type: dissertation user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2023' ... --- OA_place: publisher _id: '14422' abstract: - lang: eng text: "Animals exhibit a remarkable ability to learn and remember new behaviors, skills, and associations throughout their lifetime. These capabilities are made possible thanks to a variety of\r\nchanges in the brain throughout adulthood, regrouped under the term \"plasticity\". Some cells\r\nin the brain —neurons— and specifically changes in the connections between neurons, the\r\nsynapses, were shown to be crucial for the formation, selection, and consolidation of memories\r\nfrom past experiences. These ongoing changes of synapses across time are called synaptic\r\nplasticity. Understanding how a myriad of biochemical processes operating at individual\r\nsynapses can somehow work in concert to give rise to meaningful changes in behavior is a\r\nfascinating problem and an active area of research.\r\nHowever, the experimental search for the precise plasticity mechanisms at play in the brain\r\nis daunting, as it is difficult to control and observe synapses during learning. Theoretical\r\napproaches have thus been the default method to probe the plasticity-behavior connection. Such\r\nstudies attempt to extract unifying principles across synapses and model all observed synaptic\r\nchanges using plasticity rules: equations that govern the evolution of synaptic strengths across\r\ntime in neuronal network models. These rules can use many relevant quantities to determine\r\nthe magnitude of synaptic changes, such as the precise timings of pre- and postsynaptic\r\naction potentials, the recent neuronal activity levels, the state of neighboring synapses, etc.\r\nHowever, analytical studies rely heavily on human intuition and are forced to make simplifying\r\nassumptions about plasticity rules.\r\nIn this thesis, we aim to assist and augment human intuition in this search for plasticity rules.\r\nWe explore whether a numerical approach could automatically discover the plasticity rules\r\nthat elicit desired behaviors in large networks of interconnected neurons. This approach is\r\ndubbed meta-learning synaptic plasticity: learning plasticity rules which themselves will make\r\nneuronal networks learn how to solve a desired task. We first write all the potential plasticity\r\nmechanisms to consider using a single expression with adjustable parameters. We then optimize\r\nthese plasticity parameters using evolutionary strategies or Bayesian inference on tasks known\r\nto involve synaptic plasticity, such as familiarity detection and network stabilization.\r\nWe show that these automated approaches are powerful tools, able to complement established\r\nanalytical methods. By comprehensively screening plasticity rules at all synapse types in\r\nrealistic, spiking neuronal network models, we discover entire sets of degenerate plausible\r\nplasticity rules that reliably elicit memory-related behaviors. Our approaches allow for more\r\nrobust experimental predictions, by abstracting out the idiosyncrasies of individual plasticity\r\nrules, and provide fresh insights on synaptic plasticity in spiking network models.\r\n" alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Basile J full_name: Confavreux, Basile J id: C7610134-B532-11EA-BD9F-F5753DDC885E last_name: Confavreux citation: ama: 'Confavreux BJ. Synapseek: Meta-learning synaptic plasticity rules. 2023. doi:10.15479/at:ista:14422' apa: 'Confavreux, B. J. (2023). Synapseek: Meta-learning synaptic plasticity rules. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:14422' chicago: 'Confavreux, Basile J. “Synapseek: Meta-Learning Synaptic Plasticity Rules.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:14422.' ieee: 'B. J. Confavreux, “Synapseek: Meta-learning synaptic plasticity rules,” Institute of Science and Technology Austria, 2023.' ista: 'Confavreux BJ. 2023. Synapseek: Meta-learning synaptic plasticity rules. Institute of Science and Technology Austria.' mla: 'Confavreux, Basile J. Synapseek: Meta-Learning Synaptic Plasticity Rules. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:14422.' short: 'B.J. Confavreux, Synapseek: Meta-Learning Synaptic Plasticity Rules, Institute of Science and Technology Austria, 2023.' corr_author: '1' date_created: 2023-10-12T14:13:25Z date_published: 2023-10-12T00:00:00Z date_updated: 2026-04-07T13:53:13Z day: '12' ddc: - '610' degree_awarded: PhD department: - _id: GradSch - _id: TiVo doi: 10.15479/at:ista:14422 ec_funded: 1 file: - access_level: open_access checksum: 7f636555eae7803323df287672fd13ed content_type: application/pdf creator: cchlebak date_created: 2023-10-12T14:53:50Z date_updated: 2024-10-13T22:30:04Z embargo: 2024-10-12 file_id: '14424' file_name: Confavreux_Thesis_2A.pdf file_size: 30599717 relation: main_file - access_level: closed checksum: 725e85946db92290a4583a0de9779e1b content_type: application/x-zip-compressed creator: cchlebak date_created: 2023-10-18T07:38:34Z date_updated: 2024-10-13T22:30:04Z embargo_to: open_access file_id: '14440' file_name: Confavreux Thesis.zip file_size: 68406739 relation: source_file file_date_updated: 2024-10-13T22:30:04Z has_accepted_license: '1' language: - iso: eng month: '10' oa: 1 oa_version: Published Version page: '148' project: - _id: 0aacfa84-070f-11eb-9043-d7eb2c709234 call_identifier: H2020 grant_number: '819603' name: Learning the shape of synaptic plasticity rules for neuronal architectures and function through machine learning. publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '9633' relation: part_of_dissertation status: public status: public supervisor: - first_name: Tim P full_name: Vogels, Tim P id: CB6FF8D2-008F-11EA-8E08-2637E6697425 last_name: Vogels orcid: 0000-0003-3295-6181 title: 'Synapseek: Meta-learning synaptic plasticity rules' tmp: image: /images/cc_by_nc_sa.png legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) short: CC BY-NC-SA (4.0) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2023' ... --- OA_place: publisher _id: '12809' abstract: - lang: eng text: "Understanding the mechanisms of learning and memory formation has always been one of\r\nthe main goals in neuroscience. Already Pavlov (1927) in his early days has used his classic\r\nconditioning experiments to study the neural mechanisms governing behavioral adaptation.\r\nWhat was not known back then was that the part of the brain that is largely responsible for\r\nthis type of associative learning is the cerebellum.\r\nSince then, plenty of theories on cerebellar learning have emerged. Despite their differences,\r\none thing they all have in common is that learning relies on synaptic and intrinsic plasticity.\r\nThe goal of my PhD project was to unravel the molecular mechanisms underlying synaptic\r\nplasticity in two synapses that have been shown to be implicated in motor learning, in an\r\neffort to understand how learning and memory formation are processed in the cerebellum.\r\nOne of the earliest and most well-known cerebellar theories postulates that motor learning\r\nlargely depends on long-term depression at the parallel fiber-Purkinje cell (PC-PC) synapse.\r\nHowever, the discovery of other types of plasticity in the cerebellar circuitry, like long-term\r\npotentiation (LTP) at the PC-PC synapse, potentiation of molecular layer interneurons (MLIs),\r\nand plasticity transfer from the cortex to the cerebellar/ vestibular nuclei has increased the\r\npopularity of the idea that multiple sites of plasticity might be involved in learning.\r\nStill a lot remains unknown about the molecular mechanisms responsible for these types of\r\nplasticity and whether they occur during physiological learning.\r\nIn the first part of this thesis we have analyzed the variation and nanodistribution of voltagegated calcium channels (VGCCs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid\r\ntype glutamate receptors (AMPARs) on the parallel fiber-Purkinje cell synapse after vestibuloocular reflex phase reversal adaptation, a behavior that has been suggested to rely on PF-PC\r\nLTP. We have found that on the last day of adaptation there is no learning trace in form of\r\nVGCCs nor AMPARs variation at the PF-PC synapse, but instead a decrease in the number of\r\nPF-PC synapses. These data seem to support the view that learning is only stored in the\r\ncerebellar cortex in an initial learning phase, being transferred later to the vestibular nuclei.\r\nNext, we have studied the role of MLIs in motor learning using a relatively simple and well characterized behavioral paradigm – horizontal optokinetic reflex (HOKR) adaptation. We\r\nhave found behavior-induced MLI potentiation in form of release probability increase that\r\ncould be explained by the increase of VGCCs at the presynaptic side. Our results strengthen\r\nthe idea of distributed cerebellar plasticity contributing to learning and provide a novel\r\nmechanism for release probability increase. " acknowledged_ssus: - _id: EM-Fac - _id: Bio - _id: PreCl alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Catarina full_name: Alcarva, Catarina id: 3A96634C-F248-11E8-B48F-1D18A9856A87 last_name: Alcarva citation: ama: 'Alcarva C. Plasticity in the cerebellum: What molecular mechanisms are behind physiological learning. 2023. doi:10.15479/at:ista:12809' apa: 'Alcarva, C. (2023). Plasticity in the cerebellum: What molecular mechanisms are behind physiological learning. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12809' chicago: 'Alcarva, Catarina. “Plasticity in the Cerebellum: What Molecular Mechanisms Are behind Physiological Learning.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:12809.' ieee: 'C. Alcarva, “Plasticity in the cerebellum: What molecular mechanisms are behind physiological learning,” Institute of Science and Technology Austria, 2023.' ista: 'Alcarva C. 2023. Plasticity in the cerebellum: What molecular mechanisms are behind physiological learning. Institute of Science and Technology Austria.' mla: 'Alcarva, Catarina. Plasticity in the Cerebellum: What Molecular Mechanisms Are behind Physiological Learning. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:12809.' short: 'C. Alcarva, Plasticity in the Cerebellum: What Molecular Mechanisms Are behind Physiological Learning, Institute of Science and Technology Austria, 2023.' corr_author: '1' date_created: 2023-04-06T07:54:09Z date_published: 2023-04-06T00:00:00Z date_updated: 2026-04-07T13:53:28Z day: '06' ddc: - '570' degree_awarded: PhD department: - _id: GradSch - _id: RySh doi: 10.15479/at:ista:12809 file: - access_level: open_access checksum: 35b5997d2b0acb461f9d33d073da0df5 content_type: application/pdf creator: cchlebak date_created: 2023-04-07T06:16:06Z date_updated: 2024-04-08T22:30:03Z embargo: 2024-04-07 file_id: '12814' file_name: Thesis_CatarinaAlcarva_final pdfA.pdf file_size: 9881969 relation: main_file - access_level: closed checksum: 81198f63c294890f6d58e8b29782efdc content_type: application/pdf creator: cchlebak date_created: 2023-04-07T06:17:11Z date_updated: 2024-04-08T22:30:03Z embargo_to: open_access file_id: '12815' file_name: Thesis_CatarinaAlcarva_final_for printing.pdf file_size: 44201583 relation: source_file - access_level: closed checksum: 0317bf7f457bb585f99d453ffa69eb53 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: cchlebak date_created: 2023-04-07T06:18:05Z date_updated: 2024-04-08T22:30:03Z embargo_to: open_access file_id: '12816' file_name: Thesis_CatarinaAlcarva_final.docx file_size: 84731244 relation: source_file file_date_updated: 2024-04-08T22:30:03Z has_accepted_license: '1' language: - iso: eng month: '04' oa: 1 oa_version: Published Version page: '115' project: - _id: 267DFB90-B435-11E9-9278-68D0E5697425 name: 'Plasticity in the cerebellum: Which molecular mechanisms are behind physiological learning?' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria status: public supervisor: - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 title: 'Plasticity in the cerebellum: What molecular mechanisms are behind physiological learning' type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2023' ... --- OA_place: publisher _id: '14622' abstract: - lang: eng text: "This Ph.D. thesis presents a detailed investigation into Variational Quantum Algorithms\r\n(VQAs), a promising class of quantum algorithms that are well suited for near-term quantum\r\ncomputation due to their moderate hardware requirements and resilience to noise. Our\r\nprimary focus lies on two particular types of VQAs: the Quantum Approximate Optimization\r\nAlgorithm (QAOA), used for solving binary optimization problems, and the Variational Quantum\r\nEigensolver (VQE), utilized for finding ground states of quantum many-body systems.\r\nIn the first part of the thesis, we examine the issue of effective parameter initialization for\r\nthe QAOA. The work demonstrates that random initialization of the QAOA often leads to\r\nconvergence in local minima with sub-optimal performance. To mitigate this issue, we propose\r\nan initialization of QAOA parameters based on the Trotterized Quantum Annealing (TQA).\r\nWe show that TQA initialization leads to the same performance as the best of an exponentially\r\nscaling number of random initializations.\r\nThe second study introduces Transition States (TS), stationary points with a single direction\r\nof descent, as a tool for systematically exploring the QAOA optimization landscape. This\r\nleads us to propose a novel greedy parameter initialization strategy that guarantees for the\r\nenergy to decrease with increasing number of circuit layers.\r\nIn the third section, we extend the QAOA to qudit systems, which are higher-dimensional\r\ngeneralizations of qubits. This chapter provides theoretical insights and practical strategies for\r\nleveraging the increased computational power of qudits in the context of quantum optimization\r\nalgorithms and suggests a quantum circuit for implementing the algorithm on an ion trap\r\nquantum computer.\r\nFinally, we propose an algorithm to avoid “barren plateaus”, regions in parameter space with\r\nvanishing gradients that obstruct efficient parameter optimization. This novel approach relies\r\non defining a notion of weak barren plateaus based on the entropies of local reduced density\r\nmatrices and showcases how these can be efficiently quantified using shadow tomography.\r\nTo illustrate the approach we employ the strategy in the VQE and show that it allows to\r\nsuccessfully avoid barren plateaus in the initialization and throughout the optimization.\r\nTaken together, this thesis greatly enhances our understanding of parameter initialization and\r\noptimization in VQAs, expands the scope of QAOA to higher-dimensional quantum systems,\r\nand presents a method to address the challenge of barren plateaus using the VQE. These\r\ninsights are instrumental in advancing the field of near-term quantum computation." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Stefan full_name: Sack, Stefan id: dd622248-f6e0-11ea-865d-ce382a1c81a5 last_name: Sack orcid: 0000-0001-5400-8508 citation: ama: 'Sack S. Improving variational quantum algorithms : Innovative initialization techniques and extensions to qudit systems. 2023. doi:10.15479/at:ista:14622' apa: 'Sack, S. (2023). Improving variational quantum algorithms : Innovative initialization techniques and extensions to qudit systems. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:14622' chicago: 'Sack, Stefan. “Improving Variational Quantum Algorithms : Innovative Initialization Techniques and Extensions to Qudit Systems.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:14622.' ieee: 'S. Sack, “Improving variational quantum algorithms : Innovative initialization techniques and extensions to qudit systems,” Institute of Science and Technology Austria, 2023.' ista: 'Sack S. 2023. Improving variational quantum algorithms : Innovative initialization techniques and extensions to qudit systems. Institute of Science and Technology Austria.' mla: 'Sack, Stefan. Improving Variational Quantum Algorithms : Innovative Initialization Techniques and Extensions to Qudit Systems. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:14622.' short: 'S. Sack, Improving Variational Quantum Algorithms : Innovative Initialization Techniques and Extensions to Qudit Systems, Institute of Science and Technology Austria, 2023.' corr_author: '1' date_created: 2023-11-28T10:58:13Z date_published: 2023-11-30T00:00:00Z date_updated: 2026-04-07T13:53:47Z day: '30' ddc: - '530' degree_awarded: PhD department: - _id: GradSch - _id: MaSe doi: 10.15479/at:ista:14622 ec_funded: 1 file: - access_level: open_access checksum: 068fd3570506ec42b2faa390de784bc4 content_type: application/pdf creator: ssack date_created: 2023-11-30T15:53:10Z date_updated: 2024-11-30T23:30:03Z embargo: 2024-11-30 file_id: '14635' file_name: PhD_Thesis.pdf file_size: 11947523 relation: main_file - access_level: closed checksum: 0fa3bc0d108aed0ac59d2c6beef2220a content_type: application/zip creator: ssack date_created: 2023-11-30T15:54:11Z date_updated: 2024-11-30T23:30:03Z embargo_to: open_access file_id: '14636' file_name: PhD Thesis (1).zip file_size: 18422964 relation: source_file file_date_updated: 2024-11-30T23:30:03Z has_accepted_license: '1' language: - iso: eng month: '11' oa: 1 oa_version: Published Version page: '142' project: - _id: bd660c93-d553-11ed-ba76-fb0fb6f49c0d name: IMB PhD Nomination Fellowship - Stefan Sack - _id: 23841C26-32DE-11EA-91FC-C7463DDC885E call_identifier: H2020 grant_number: '850899' name: 'Non-Ergodic Quantum Matter: Universality, Dynamics and Control' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '13125' relation: part_of_dissertation status: public - id: '11471' relation: part_of_dissertation status: public - id: '9760' relation: part_of_dissertation status: public status: public supervisor: - first_name: Maksym full_name: Serbyn, Maksym id: 47809E7E-F248-11E8-B48F-1D18A9856A87 last_name: Serbyn orcid: 0000-0002-2399-5827 title: 'Improving variational quantum algorithms : Innovative initialization techniques and extensions to qudit systems' tmp: image: /images/cc_by_nc_sa.png legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) short: CC BY-NC-SA (4.0) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2023' ... --- OA_place: publisher _id: '14697' abstract: - lang: eng text: "During my Ph.D. research, I managed a series of projects, each focused on the\r\nmechanisms underlying cell migration. My work involved an in-depth examination of\r\nthe complex strategies employed by neutrophils, with a specific focus on their ability to\r\nsynchronize spatial-temporal cues and optimize their gradient perception. However, it\r\nis essential to acknowledge that not all projects yielded successful results, as some\r\nideas were discontinued and are archived for future reference within this thesis.\r\nMy main project investigated how neutrophils decode spatial cues for precise navigation. Human neutrophils showcased distinct movement patterns based on source\r\ntype – linear or point-like. By combining single-cell tracking in 3D environments with\r\nproxy dyes, this project linked cell behaviors to gradient changes, revealing a stronger\r\nresponse to semi-exponential gradients from point sources. In addition, neutrophils\r\nexhibited oscillating migration speeds, using speed minima to adjust trajectories toward sources. Experiencing continuous concentration changes, they accelerated over\r\ntime and employed a \"Run and Fumble\" strategy, alternating between consistent runs\r\nand strategic \"tumbles\" for efficient navigation.\r\nThe project extended to the possibility of cells amplifying perceived gradients by\r\nenclosing their immediate surroundings, pushing attractants forward for enrichment\r\nwhile depleting it at the cell rear. Microfluidic devices were employed, and various experimental parameters configurations were optimized. Although significant differences\r\nin migratory efficacy were detected across pore sizes and device heights, quantifying\r\ngradient manipulation effects proved challenging.\r\nThe \"Laser-Assisted Protein Adsorption by Photobleaching\" (LAPAP) project was\r\npromising, as it allowed the printing of gradients. Initially successful with dendritic cells,\r\nwe aimed to adapt it for neutrophils. Through extensive experimentation with multiple\r\nparameters, we attempted to trigger responses from neutrophils. Despite these efforts\r\nand collaboration, the project failed due to practical challenges and limitations.\r\nFacing a lack of neutrophil-like cells at IST, we initially established the SCF-HoxB8\r\nprimary murine cell line. Despite their existence, their migratory behavior was largely\r\nunexplored due to potential limitations. Through differentiation protocol refinements we\r\nenhanced their migratory capabilities, though their capacity still lagged behind human\r\nneutrophils. Despite this, the improved migration potential of these cells pointed toward\r\ntheir utility for in vitro murine neutrophil migration studies." acknowledged_ssus: - _id: LifeSc - _id: Bio alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Julian A full_name: Stopp, Julian A id: 489E3F00-F248-11E8-B48F-1D18A9856A87 last_name: Stopp citation: ama: 'Stopp JA. Neutrophils on the hunt : Migratory strategies employed by neutrophils to fulfill their effector function. 2023. doi:10.15479/at:ista:14697' apa: 'Stopp, J. A. (2023). Neutrophils on the hunt : Migratory strategies employed by neutrophils to fulfill their effector function. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:14697' chicago: 'Stopp, Julian A. “Neutrophils on the Hunt : Migratory Strategies Employed by Neutrophils to Fulfill Their Effector Function.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:14697.' ieee: 'J. A. Stopp, “Neutrophils on the hunt : Migratory strategies employed by neutrophils to fulfill their effector function,” Institute of Science and Technology Austria, 2023.' ista: 'Stopp JA. 2023. Neutrophils on the hunt : Migratory strategies employed by neutrophils to fulfill their effector function. Institute of Science and Technology Austria.' mla: 'Stopp, Julian A. Neutrophils on the Hunt : Migratory Strategies Employed by Neutrophils to Fulfill Their Effector Function. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:14697.' short: 'J.A. Stopp, Neutrophils on the Hunt : Migratory Strategies Employed by Neutrophils to Fulfill Their Effector Function, Institute of Science and Technology Austria, 2023.' corr_author: '1' date_created: 2023-12-18T19:14:28Z date_published: 2023-12-20T00:00:00Z date_updated: 2026-04-07T13:57:40Z day: '20' ddc: - '570' degree_awarded: PhD department: - _id: GradSch - _id: MiSi doi: 10.15479/at:ista:14697 ec_funded: 1 file: - access_level: open_access checksum: 457927165d5d556305d3086f6b83e5c7 content_type: application/pdf creator: jstopp date_created: 2023-12-20T09:35:34Z date_updated: 2024-12-20T23:30:04Z embargo: 2024-12-20 file_id: '14699' file_name: Thesis.pdf file_size: 51585778 relation: main_file - access_level: closed checksum: e8d26449ac461f5e8478a62c9507506f content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: jstopp date_created: 2023-12-20T09:35:35Z date_updated: 2024-12-20T23:30:04Z embargo_to: open_access file_id: '14700' file_name: Thesis.docx file_size: 69625950 relation: source_file file_date_updated: 2024-12-20T23:30:04Z has_accepted_license: '1' language: - iso: eng month: '12' oa: 1 oa_version: Published Version page: '226' project: - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program publication_identifier: isbn: - 978-3-99078-038-1 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '14360' relation: part_of_dissertation status: public - id: '12272' relation: part_of_dissertation status: public - id: '14274' relation: part_of_dissertation status: public - id: '6328' relation: part_of_dissertation status: public - id: '7885' 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: 0000-0002-6620-9179 title: 'Neutrophils on the hunt : Migratory strategies employed by neutrophils to fulfill their effector function' type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2023' ... --- OA_place: publisher _id: '14280' abstract: - lang: eng text: "Cell division in Escherichia coli is performed by the divisome, a multi-protein complex composed of more than 30 proteins. The divisome spans from the cytoplasm through the inner membrane to the cell wall and the outer membrane. Divisome assembly is initiated by a cytoskeletal structure, the so-called Z-ring, which localizes at the center of the E. coli cell and determines the position of the future cell septum. The Z-ring is composed of the highly conserved bacterial tubulin homologue FtsZ, which forms treadmilling filaments. These filaments are recruited to the inner membrane by FtsA, a highly conserved bacterial actin homologue. FtsA interacts with other proteins in the periplasm and thus connects the cytoplasmic and periplasmic components of the divisome. \r\nA previous model postulated that FtsA regulates maturation of the divisome by switching from an oligomeric, inactive state to a monomeric and active state. This model was based mostly on in vivo studies, as a biochemical characterization of FtsA has been hampered by difficulties in purifying the protein. Here, we studied FtsA using an in vitro reconstitution approach and aimed to answer two questions: (i) How are dynamics from cytoplasmic, treadmilling FtsZ filaments coupled to proteins acting in the periplasmic space and (ii) How does FtsA regulate the maturation of the divisome?\r\nWe found that the cytoplasmic peptides of the transmembrane proteins FtsN and FtsQ interact directly with FtsA and can follow the spatiotemporal signal of FtsA/Z filaments. When we investigated the underlying mechanism by imaging single molecules of FtsNcyto, we found the peptide to interact transiently with FtsA. An in depth analysis of the single molecule trajectories helped to postulate a model where PG synthases follow the dynamics of FtsZ by a diffusion and capture mechanism. \r\nFollowing up on these findings we were interested in how the self-interaction of FtsA changes when it encounters FtsNcyto and if we can confirm the proposed oligomer-monomer switch. For this, we compared the behavior of the previously identified, hyperactive mutant FtsA R286W with wildtype FtsA. The mutant outperforms WT in mirroring and transmitting the spatiotemporal signal of treadmilling FtsZ filaments. Surprisingly however, we found that this was not due to a difference in the self-interaction strength of the two variants, but a difference in their membrane residence time. Furthermore, in contrast to our expectations, upon binding of FtsNcyto the measured self-interaction of FtsA actually increased. \r\nWe propose that FtsNcyto induces a rearrangement of the oligomeric architecture of FtsA. In further consequence this change leads to more persistent FtsZ filaments which results in a defined signalling zone, allowing formation of the mature divisome. The observed difference between FtsA WT and R286W is due to the vastly different membrane turnover of the proteins. R286W cycles 5-10x faster compared to WT which allows to sample FtsZ filaments at faster frequencies. These findings can explain the observed differences in toxicity for overexpression of FtsA WT and R286W and help to understand how FtsA regulates divisome maturation." acknowledged_ssus: - _id: Bio - _id: LifeSc alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Philipp full_name: Radler, Philipp id: 40136C2A-F248-11E8-B48F-1D18A9856A87 last_name: Radler orcid: '0000-0001-9198-2182 ' citation: ama: Radler P. Spatiotemporal signaling during assembly of the bacterial divisome. 2023. doi:10.15479/at:ista:14280 apa: Radler, P. (2023). Spatiotemporal signaling during assembly of the bacterial divisome. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:14280 chicago: Radler, Philipp. “Spatiotemporal Signaling during Assembly of the Bacterial Divisome.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:14280. ieee: P. Radler, “Spatiotemporal signaling during assembly of the bacterial divisome,” Institute of Science and Technology Austria, 2023. ista: Radler P. 2023. Spatiotemporal signaling during assembly of the bacterial divisome. Institute of Science and Technology Austria. mla: Radler, Philipp. Spatiotemporal Signaling during Assembly of the Bacterial Divisome. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:14280. short: P. Radler, Spatiotemporal Signaling during Assembly of the Bacterial Divisome, Institute of Science and Technology Austria, 2023. corr_author: '1' date_created: 2023-09-06T10:58:25Z date_published: 2023-09-25T00:00:00Z date_updated: 2026-04-07T14:06:05Z day: '25' ddc: - '572' degree_awarded: PhD department: - _id: GradSch - _id: MaLo doi: 10.15479/at:ista:14280 ec_funded: 1 file: - access_level: closed checksum: 87eef11fbc5c7df0826f12a3a629b444 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: pradler date_created: 2023-10-04T10:11:53Z date_updated: 2024-10-05T22:30:03Z embargo_to: open_access file_id: '14390' file_name: PhD Thesis_Philipp Radler_20231004.docx file_size: 114932847 relation: source_file - access_level: open_access checksum: 3253e099b7126469d941fd9419d68b4f content_type: application/pdf creator: pradler date_created: 2023-10-04T10:11:21Z date_updated: 2024-10-05T22:30:03Z embargo: 2024-10-04 file_id: '14391' file_name: PhD Thesis_Philipp Radler_20231004.pdf file_size: 37838778 relation: main_file file_date_updated: 2024-10-05T22:30:03Z has_accepted_license: '1' keyword: - Cell Division - Reconstitution - FtsZ - FtsA - Divisome - E.coli language: - iso: eng month: '09' oa: 1 oa_version: Published Version page: '156' project: - _id: 2595697A-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '679239' name: Self-Organization of the Bacterial Cell - _id: fc38323b-9c52-11eb-aca3-ff8afb4a011d grant_number: P34607 name: In vitro reconstitution of bacterial cell division - _id: 2596EAB6-B435-11E9-9278-68D0E5697425 grant_number: ALTF 2015-1163 name: Synthesis of bacterial cell wall - _id: 259B655A-B435-11E9-9278-68D0E5697425 grant_number: LT000824/2016 name: Reconstitution of bacterial cell wall synthesis publication_identifier: isbn: - 978-3-99078-033-6 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '10934' relation: research_data status: public - id: '11373' relation: part_of_dissertation status: public - id: '7387' relation: part_of_dissertation status: public status: public supervisor: - first_name: Martin full_name: Loose, Martin id: 462D4284-F248-11E8-B48F-1D18A9856A87 last_name: Loose orcid: 0000-0001-7309-9724 title: Spatiotemporal signaling during assembly of the bacterial divisome 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) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2023' ... --- OA_place: publisher _id: '12781' abstract: - lang: eng text: "Most energy in humans is produced in form of ATP by the mitochondrial respiratory chain consisting of several protein assemblies embedded into lipid membrane (complexes I-V). Complex I is the first and the largest enzyme of the respiratory chain which is essential for energy production. It couples the transfer of two electrons from NADH to ubiquinone with proton translocation across bacterial or inner mitochondrial membrane. The coupling mechanism between electron transfer and proton translocation is one of the biggest enigma in bioenergetics and structural biology. Even though the enzyme has been studied for decades, only recent technological advances in cryo-EM allowed its extensive structural investigation. \r\n\r\nComplex I from E.coli appears to be of special importance because it is a perfect model system with a rich mutant library, however the structure of the entire complex was unknown. In this thesis I have resolved structures of the minimal complex I version from E. coli in different states including reduced, inhibited, under reaction turnover and several others. Extensive structural analyses of these structures and comparison to structures from other species allowed to derive general features of conformational dynamics and propose a universal coupling mechanism. The mechanism is straightforward, robust and consistent with decades of experimental data available for complex I from different species. \r\n\r\nCyanobacterial NDH (cyanobacterial complex I) is a part of broad complex I superfamily and was studied as well in this thesis. It plays an important role in cyclic electron transfer (CET), during which electrons are cycled within PSI through ferredoxin and plastoquinone to generate proton gradient without NADPH production. Here, I solved structure of NDH and revealed additional state, which was not observed before. The novel “resting” state allowed to propose the mechanism of CET regulation. Moreover, conformational dynamics of NDH resembles one in complex I which suggest more broad universality of the proposed coupling mechanism.\r\n\r\nIn summary, results presented here helped to interpret decades of experimental data for complex I and contributed to fundamental mechanistic understanding of protein function.\r\n" acknowledged_ssus: - _id: EM-Fac alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Vladyslav full_name: Kravchuk, Vladyslav id: 4D62F2A6-F248-11E8-B48F-1D18A9856A87 last_name: Kravchuk orcid: 0000-0001-9523-9089 citation: ama: Kravchuk V. Structural and mechanistic study of bacterial complex I and its cyanobacterial ortholog. 2023. doi:10.15479/at:ista:12781 apa: Kravchuk, V. (2023). Structural and mechanistic study of bacterial complex I and its cyanobacterial ortholog. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12781 chicago: Kravchuk, Vladyslav. “Structural and Mechanistic Study of Bacterial Complex I and Its Cyanobacterial Ortholog.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:12781. ieee: V. Kravchuk, “Structural and mechanistic study of bacterial complex I and its cyanobacterial ortholog,” Institute of Science and Technology Austria, 2023. ista: Kravchuk V. 2023. Structural and mechanistic study of bacterial complex I and its cyanobacterial ortholog. Institute of Science and Technology Austria. mla: Kravchuk, Vladyslav. Structural and Mechanistic Study of Bacterial Complex I and Its Cyanobacterial Ortholog. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:12781. short: V. Kravchuk, Structural and Mechanistic Study of Bacterial Complex I and Its Cyanobacterial Ortholog, Institute of Science and Technology Austria, 2023. corr_author: '1' date_created: 2023-03-31T12:24:42Z date_published: 2023-03-23T00:00:00Z date_updated: 2026-04-07T14:10:40Z day: '23' ddc: - '570' - '572' degree_awarded: PhD department: - _id: GradSch - _id: LeSa doi: 10.15479/at:ista:12781 ec_funded: 1 file: - access_level: open_access checksum: 5ebb6345cb4119f93460c81310265a6d content_type: application/pdf creator: vkravchu date_created: 2023-04-19T14:33:41Z date_updated: 2024-04-22T22:30:06Z embargo: 2024-04-20 file_id: '12852' file_name: VladyslavKravchuk_PhD_Thesis_PostSub_Final_1.pdf file_size: 6071553 relation: main_file - access_level: open_access checksum: c12055c48411d030d2afa51de2166221 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: vkravchu date_created: 2023-04-19T14:33:52Z date_updated: 2024-04-22T22:30:06Z embargo: 2024-04-20 file_id: '12853' file_name: VladyslavKravchuk_PhD_Thesis_PostSub_Final.docx file_size: 19468766 relation: source_file file_date_updated: 2024-04-22T22:30:06Z has_accepted_license: '1' language: - iso: eng month: '03' oa: 1 oa_version: Published Version page: '127' project: - _id: 238A0A5A-32DE-11EA-91FC-C7463DDC885E grant_number: '25541' name: 'Structural characterization of E. coli complex I: an important mechanistic model' - _id: 627abdeb-2b32-11ec-9570-ec31a97243d3 call_identifier: H2020 grant_number: '101020697' name: Structure and mechanism of respiratory chain molecular machines publication_identifier: isbn: - 978-3-99078-029-9 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '12138' relation: part_of_dissertation status: public status: public supervisor: - first_name: Leonid A full_name: Sazanov, Leonid A id: 338D39FE-F248-11E8-B48F-1D18A9856A87 last_name: Sazanov orcid: 0000-0002-0977-7989 title: Structural and mechanistic study of bacterial complex I and its cyanobacterial ortholog type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2023' ... --- OA_place: publisher _id: '14510' abstract: - lang: eng text: "Clathrin-mediated endocytosis (CME) is vital for the regulation of plant growth and\r\ndevelopment by controlling plasma membrane protein composition and cargo uptake. CME\r\nrelies on the precise recruitment control of protein regulators for vesicle maturation and\r\nrelease. During the early stages of endocytosis, an area of flat membrane is remodelled by\r\nproteins to create a spherical vesicle against intracellular forces. After the Clathrin-coated\r\nvesicle (CCV) is fully formed, scission machinery releases it from the plasma membrane,\r\nand cargo proceeds for recycling or degradation through early endosomes / Trans Golgi\r\nnetwork. Protein machineries that mediate membrane bending and vesicle release in plants\r\nare unknown. However, studies show, that plant endocytosis is actin independent, thus\r\nindicating that plants utilize a unique mechanism to mediate membrane bending against highturgor pressure compared to other model systems. First, by using biochemical and advanced\r\nlive microscopy approaches we investigate the TPLATE complex, a plant-specific\r\nendocytosis protein complex. We found that TPLATE is peripherally associated with\r\nclathrin-coated vesicles and localises at the rim of endocytosis events. Next, our study of\r\nplant Dynamin-related protein 1C (DRP1C), which was hypothesised previously to play a\r\nrole in vesicle release, shows the recruitment of the protein already at the early stages of\r\nendocytosis. Moreover, DRP1C assembles into organised ring-like structures and is able to\r\ninduce membrane deformation and tubulation, suggesting its role also in membrane bending\r\nduring early CME. Based on the data from mammalian and yeast systems, plant DynaminRelated Proteins 2 and SH3P2 protein are strong candidates to be part of the plant vesicle\r\nscission machinery; however, their precise role in plant CME has not been yet elucidated.\r\nHere, we characterised DRP2s and SH3P2 roles in CME by combining high-resolution\r\nimaging of endocytic events in vivo and protein characterisation. Although DRP2s and\r\nSH3P2 arrive together during late CME and physically interact, genetic analysis using\r\n∆sh3p1,2,3 mutant and complementation with non-DRP2-interacting SH3P2 variants suggest\r\nthat SH3P2 does not directly recruit DRP2s to the site of endocytosis. Summarising our\r\nresearch, these observations provide new important insights into the mechanism of plant\r\nCME and show that, despite plants posses many homologues of mammalian and yeast CME\r\ncomponents, they do not necessarily act in the same manner. " acknowledged_ssus: - _id: EM-Fac - _id: Bio - _id: LifeSc alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Nataliia full_name: Gnyliukh, Nataliia id: 390C1120-F248-11E8-B48F-1D18A9856A87 last_name: Gnyliukh orcid: 0000-0002-2198-0509 citation: ama: Gnyliukh N. Mechanism of clathrin-coated vesicle  formation during endocytosis in plants. 2023. doi:10.15479/at:ista:14510 apa: Gnyliukh, N. (2023). Mechanism of clathrin-coated vesicle  formation during endocytosis in plants. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:14510 chicago: Gnyliukh, Nataliia. “Mechanism of Clathrin-Coated Vesicle  Formation during Endocytosis in Plants.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:14510. ieee: N. Gnyliukh, “Mechanism of clathrin-coated vesicle  formation during endocytosis in plants,” Institute of Science and Technology Austria, 2023. ista: Gnyliukh N. 2023. Mechanism of clathrin-coated vesicle  formation during endocytosis in plants. Institute of Science and Technology Austria. mla: Gnyliukh, Nataliia. Mechanism of Clathrin-Coated Vesicle  Formation during Endocytosis in Plants. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:14510. short: N. Gnyliukh, Mechanism of Clathrin-Coated Vesicle  Formation during Endocytosis in Plants, Institute of Science and Technology Austria, 2023. corr_author: '1' date_created: 2023-11-10T09:10:06Z date_published: 2023-11-10T00:00:00Z date_updated: 2026-05-15T22:30:39Z day: '10' ddc: - '570' degree_awarded: PhD department: - _id: GradSch - _id: JiFr - _id: MaLo doi: 10.15479/at:ista:14510 ec_funded: 1 file: - access_level: closed checksum: 3d5e680bfc61f98e308c434f45cc9bd6 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: ngnyliuk date_created: 2023-11-20T09:18:51Z date_updated: 2024-11-23T23:30:38Z embargo_to: open_access file_id: '14567' file_name: Thesis_Gnyliukh_final_08_11_23.docx file_size: 20824903 relation: source_file - access_level: open_access checksum: bfc96d47fc4e7e857dd71656097214a4 content_type: application/pdf creator: ngnyliuk date_created: 2023-11-20T09:23:11Z date_updated: 2024-11-23T23:30:38Z embargo: 2024-11-23 file_id: '14568' file_name: Thesis_Gnyliukh_final_20_11_23.pdf file_size: 24871844 relation: main_file file_date_updated: 2024-11-23T23:30:38Z has_accepted_license: '1' keyword: - Clathrin-Mediated Endocytosis - vesicle scission - Dynamin-Related Protein 2 - SH3P2 - TPLATE complex - Total internal reflection fluorescence microscopy - Arabidopsis thaliana language: - iso: eng month: '11' oa: 1 oa_version: Published Version page: '180' project: - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program publication_identifier: isbn: - 978-3-99078-037-4 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '14591' relation: part_of_dissertation status: public - id: '9887' relation: part_of_dissertation status: public - id: '8139' relation: part_of_dissertation status: public status: public supervisor: - first_name: Jiří full_name: Friml, Jiří id: 4159519E-F248-11E8-B48F-1D18A9856A87 last_name: Friml orcid: 0000-0002-8302-7596 - first_name: Martin full_name: Loose, Martin id: 462D4284-F248-11E8-B48F-1D18A9856A87 last_name: Loose orcid: 0000-0001-7309-9724 title: Mechanism of clathrin-coated vesicle formation during endocytosis in plants 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) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2023' ... --- OA_place: publisher _id: '12470' abstract: - lang: eng text: "The brain is an exceptionally sophisticated organ consisting of billions of cells and trillions of \r\nconnections that orchestrate our cognition and behavior. To decode its complex connectivity, it is \r\npivotal to disentangle its intricate architecture spanning from cm-sized circuits down to tens of \r\nnm-small synapses.\r\nTo achieve this goal, I developed CATS – Comprehensive Analysis of nervous Tissue across \r\nScales, a versatile toolbox for obtaining a holistic view of nervous tissue context with (super\x02resolution) fluorescence microscopy. CATS combines comprehensive labeling of the extracellular\r\nspace, that is compatible with chemical fixation, with information on molecular markers, super\x02resolved data acquisition and machine-learning based data analysis for segmentation and synapse \r\nidentification.\r\nI used CATS to analyze key features of nervous tissue connectivity, ranging from whole tissue \r\narchitecture, neuronal in- and output-fields, down to synapse morphology.\r\nFocusing on the hippocampal circuitry, I quantified synaptic transmission properties of mossy \r\nfiber boutons and analyzed the connectivity pattern of dentate gyrus granule cells with CA3 \r\npyramidal neurons. This shows that CATS is a viable tool to study hallmarks of neuronal \r\nconnectivity with light microscopy." acknowledged_ssus: - _id: Bio - _id: LifeSc - _id: PreCl - _id: EM-Fac - _id: M-Shop - _id: ScienComp alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Julia M full_name: Michalska, Julia M id: 443DB6DE-F248-11E8-B48F-1D18A9856A87 last_name: Michalska orcid: 0000-0003-3862-1235 citation: ama: Michalska JM. A versatile toolbox for the comprehensive analysis of nervous tissue organization with light microscopy. 2023. doi:10.15479/at:ista:12470 apa: Michalska, J. M. (2023). A versatile toolbox for the comprehensive analysis of nervous tissue organization with light microscopy. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12470 chicago: Michalska, Julia M. “A Versatile Toolbox for the Comprehensive Analysis of Nervous Tissue Organization with Light Microscopy.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:12470. ieee: J. M. Michalska, “A versatile toolbox for the comprehensive analysis of nervous tissue organization with light microscopy,” Institute of Science and Technology Austria, 2023. ista: Michalska JM. 2023. A versatile toolbox for the comprehensive analysis of nervous tissue organization with light microscopy. Institute of Science and Technology Austria. mla: Michalska, Julia M. A Versatile Toolbox for the Comprehensive Analysis of Nervous Tissue Organization with Light Microscopy. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:12470. short: J.M. Michalska, A Versatile Toolbox for the Comprehensive Analysis of Nervous Tissue Organization with Light Microscopy, Institute of Science and Technology Austria, 2023. corr_author: '1' date_created: 2023-01-31T15:10:53Z date_published: 2023-01-09T00:00:00Z date_updated: 2026-04-07T14:11:10Z day: '09' ddc: - '610' degree_awarded: PhD department: - _id: GradSch - _id: JoDa doi: 10.15479/at:ista:12470 ec_funded: 1 file: - access_level: open_access checksum: 1a2306e5f59f52df598e7ecfadf921ac content_type: application/pdf creator: cchlebak date_created: 2023-01-31T15:11:42Z date_updated: 2023-07-27T22:30:54Z embargo: 2023-07-09 file_id: '12471' file_name: 20230109_PhD_thesis_JM_final.pdf file_size: 41771714 relation: main_file - access_level: closed checksum: 0bebbdee0773443959e1f6ab8caf281f content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: cchlebak date_created: 2023-01-31T15:11:51Z date_updated: 2023-07-10T22:30:04Z embargo_to: open_access file_id: '12472' file_name: 20230109_PhD_thesis_JM_final.docx file_size: 66983464 relation: source_file file_date_updated: 2023-07-27T22:30:54Z has_accepted_license: '1' language: - iso: eng month: '01' oa: 1 oa_version: Published Version page: '201' project: - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program - _id: 26AA4EF2-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232-B24 name: Molecular Drug Targets publication_identifier: isbn: - 978-3-99078-026-8 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '11943' relation: part_of_dissertation status: public - id: '11950' relation: part_of_dissertation status: public status: public supervisor: - first_name: Johann G full_name: Danzl, Johann G id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87 last_name: Danzl orcid: 0000-0001-8559-3973 title: A versatile toolbox for the comprehensive analysis of nervous tissue organization with light microscopy 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) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2023' ... --- OA_place: publisher _id: '14323' abstract: - lang: eng text: Morphogens are signaling molecules that are known for their prominent role in pattern formation within developing tissues. In addition to patterning, morphogens also control tissue growth. However, the underlying mechanisms are poorly understood. We studied the role of morphogens in regulating tissue growth in the developing vertebrate neural tube. In this system, opposing morphogen gradients of Shh and BMP establish the dorsoventral pattern of neural progenitor domains. Perturbations in these morphogen pathways result in alterations in tissue growth and cell cycle progression, however, it has been unclear what cellular process is affected. To address this, we analysed the rates of cell proliferation and cell death in mouse mutants in which signaling is perturbed, as well as in chick neural plate explants exposed to defined concentrations of signaling activators or inhibitors. Our results indicated that the rate of cell proliferation was not altered in these assays. By contrast, both the Shh and BMP signaling pathways had profound effects on neural progenitor survival. Our results indicate that these pathways synergise to promote cell survival within neural progenitors. Consistent with this, we found that progenitors within the intermediate region of the neural tube, where the combined levels of Shh and BMP are the lowest, are most prone to cell death when signaling activity is inhibited. In addition, we found that downregulation of Shh results in increased apoptosis within the roof plate, which is the dorsal source of BMP ligand production. This revealed a cross-interaction between the Shh and BMP morphogen signaling pathways that may be relevant for understanding how gradients scale in neural tubes with different overall sizes. We further studied the mechanism acting downstream of Shh in cell survival regulation using genetic and genomic approaches. We propose that Shh transcriptionally regulates a non-canonical apoptotic pathway. Altogether, our study points to a novel role of opposing morphogen gradients in tissue size regulation and provides new insights into complex interactions between Shh and BMP signaling gradients in the neural tube. acknowledged_ssus: - _id: Bio - _id: PreCl alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Katarzyna full_name: Kuzmicz-Kowalska, Katarzyna id: 4CED352A-F248-11E8-B48F-1D18A9856A87 last_name: Kuzmicz-Kowalska citation: ama: Kuzmicz-Kowalska K. Regulation of neural progenitor survival by Shh and BMP in the developing spinal cord. 2023. doi:10.15479/at:ista:14323 apa: Kuzmicz-Kowalska, K. (2023). Regulation of neural progenitor survival by Shh and BMP in the developing spinal cord. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:14323 chicago: Kuzmicz-Kowalska, Katarzyna. “Regulation of Neural Progenitor Survival by Shh and BMP in the Developing Spinal Cord.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:14323. ieee: K. Kuzmicz-Kowalska, “Regulation of neural progenitor survival by Shh and BMP in the developing spinal cord,” Institute of Science and Technology Austria, 2023. ista: Kuzmicz-Kowalska K. 2023. Regulation of neural progenitor survival by Shh and BMP in the developing spinal cord. Institute of Science and Technology Austria. mla: Kuzmicz-Kowalska, Katarzyna. Regulation of Neural Progenitor Survival by Shh and BMP in the Developing Spinal Cord. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:14323. short: K. Kuzmicz-Kowalska, Regulation of Neural Progenitor Survival by Shh and BMP in the Developing Spinal Cord, Institute of Science and Technology Austria, 2023. corr_author: '1' date_created: 2023-09-13T10:07:18Z date_published: 2023-09-13T00:00:00Z date_updated: 2026-04-14T09:50:54Z day: '13' ddc: - '570' degree_awarded: PhD department: - _id: GradSch - _id: AnKi doi: 10.15479/at:ista:14323 file: - access_level: open_access checksum: bd83596869c814b24aeff7077d031c0e content_type: application/pdf creator: kkuzmicz date_created: 2023-09-13T09:52:52Z date_updated: 2025-03-13T23:30:05Z embargo: 2025-03-13 file_id: '14324' file_name: PhDThesis_KK_final_pdfA.pdf file_size: 10147911 relation: main_file - access_level: closed checksum: aa2757ae4c3478041fd7e62c587d3e4d content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: kkuzmicz date_created: 2023-09-13T09:53:29Z date_updated: 2025-03-13T23:30:05Z embargo_to: open_access file_id: '14325' file_name: thesis_KK_final_corrections_092023.docx file_size: 103980668 relation: source_file file_date_updated: 2025-03-13T23:30:05Z has_accepted_license: '1' language: - iso: eng month: '09' oa: 1 oa_version: Published Version page: '151' project: - _id: 267AF0E4-B435-11E9-9278-68D0E5697425 name: The role of morphogens in the regulation of neural tube growth publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '7883' relation: part_of_dissertation status: public status: public supervisor: - first_name: Anna full_name: Kicheva, Anna id: 3959A2A0-F248-11E8-B48F-1D18A9856A87 last_name: Kicheva orcid: 0000-0003-4509-4998 title: Regulation of neural progenitor survival by Shh and BMP in the developing spinal cord tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2023' ... --- OA_place: publisher _id: '13081' abstract: - lang: eng text: During development, tissues undergo changes in size and shape to form functional organs. Distinct cellular processes such as cell division and cell rearrangements underlie tissue morphogenesis. Yet how the distinct processes are controlled and coordinated, and how they contribute to morphogenesis is poorly understood. In our study, we addressed these questions using the developing mouse neural tube. This epithelial organ transforms from a flat epithelial sheet to an epithelial tube while increasing in size and undergoing morpho-gen-mediated patterning. The extent and mechanism of neural progenitor rearrangement within the developing mouse neuroepithelium is unknown. To investigate this, we per-formed high resolution lineage tracing analysis to quantify the extent of epithelial rear-rangement at different stages of neural tube development. We quantitatively described the relationship between apical cell size with cell cycle dependent interkinetic nuclear migra-tions (IKNM) and performed high cellular resolution live imaging of the neuroepithelium to study the dynamics of junctional remodeling. Furthermore, developed a vertex model of the neuroepithelium to investigate the quantitative contribution of cell proliferation, cell differentiation and mechanical properties to the epithelial rearrangement dynamics and validated the model predictions through functional experiments. Our analysis revealed that at early developmental stages, the apical cell area kinetics driven by IKNM induce high lev-els of cell rearrangements in a regime of high junctional tension and contractility. After E9.5, there is a sharp decline in the extent of cell rearrangements, suggesting that the epi-thelium transitions from a fluid-like to a solid-like state. We found that this transition is regulated by the growth rate of the tissue, rather than by changes in cell-cell adhesion and contractile forces. Overall, our study provides a quantitative description of the relationship between tissue growth, cell cycle dynamics, epithelia rearrangements and the emergent tissue material properties, and novel insights on how epithelial cell dynamics influences tissue morphogenesis. acknowledged_ssus: - _id: Bio - _id: LifeSc alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Laura full_name: Bocanegra, Laura id: 4896F754-F248-11E8-B48F-1D18A9856A87 last_name: Bocanegra citation: ama: Bocanegra L. Epithelial dynamics during mouse neural tube development. 2023. doi:10.15479/at:ista:13081 apa: Bocanegra, L. (2023). Epithelial dynamics during mouse neural tube development. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:13081 chicago: Bocanegra, Laura. “Epithelial Dynamics during Mouse Neural Tube Development.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:13081. ieee: L. Bocanegra, “Epithelial dynamics during mouse neural tube development,” Institute of Science and Technology Austria, 2023. ista: Bocanegra L. 2023. Epithelial dynamics during mouse neural tube development. Institute of Science and Technology Austria. mla: Bocanegra, Laura. Epithelial Dynamics during Mouse Neural Tube Development. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:13081. short: L. Bocanegra, Epithelial Dynamics during Mouse Neural Tube Development, Institute of Science and Technology Austria, 2023. corr_author: '1' date_created: 2023-05-23T19:10:42Z date_published: 2023-05-23T00:00:00Z date_updated: 2026-04-14T09:50:54Z day: '23' ddc: - '570' degree_awarded: PhD department: - _id: GradSch - _id: AnKi doi: 10.15479/at:ista:13081 file: - access_level: closed checksum: 74f3f89e59a0189bee53ebfad9c1b9af content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: lbocaneg date_created: 2023-05-25T06:32:12Z date_updated: 2024-06-01T22:30:04Z embargo_to: open_access file_id: '13089' file_name: Thesis_final_LauraBocanegra.docx file_size: 25615534 relation: source_file - access_level: open_access checksum: c6cdef6323eacfb4b7a8af20f32eae97 content_type: application/pdf creator: lbocaneg date_created: 2023-05-25T06:32:16Z date_updated: 2024-06-01T22:30:04Z embargo: 2024-05-31 file_id: '13090' file_name: TotalFinal_Thesis_LauraBocanegraArx.pdf file_size: 12386046 relation: main_file file_date_updated: 2024-06-01T22:30:04Z has_accepted_license: '1' language: - iso: eng month: '05' oa: 1 oa_version: Published Version page: '93' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '9349' relation: part_of_dissertation status: public - id: '12837' relation: part_of_dissertation status: public status: public supervisor: - first_name: Anna full_name: Kicheva, Anna id: 3959A2A0-F248-11E8-B48F-1D18A9856A87 last_name: Kicheva orcid: 0000-0003-4509-4998 title: Epithelial dynamics during mouse neural tube development tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2023' ... --- OA_place: publisher _id: '11128' abstract: - lang: eng text: "Although we often see studies focusing on simple or even discrete traits in studies of colouration,\r\nthe variation of “appearance” phenotypes found in nature is often more complex, continuous\r\nand high-dimensional. Therefore, we developed automated methods suitable for large datasets\r\nof genomes and images, striving to account for their complex nature, while minimising human\r\nbias. We used these methods on a dataset of more than 20, 000 plant SNP genomes and\r\ncorresponding fower images from a hybrid zone of two subspecies of Antirrhinum majus with\r\ndistinctly coloured fowers to improve our understanding of the genetic nature of the fower\r\ncolour in our study system.\r\nFirstly, we use the advantage of large numbers of genotyped plants to estimate the haplotypes in\r\nthe main fower colour regulating region. We study colour- and geography-related characteristics\r\nof the estimated haplotypes and how they connect to their relatedness. We show discrepancies\r\nfrom the expected fower colour distributions given the genotype and identify particular\r\nhaplotypes leading to unexpected phenotypes. We also confrm a signifcant defcit of the\r\ndouble recessive recombinant and quite surprisingly, we show that haplotypes of the most\r\nfrequent parental type are much less variable than others.\r\nSecondly, we introduce our pipeline capable of processing tens of thousands of full fower\r\nimages without human interaction and summarising each image into a set of informative scores.\r\nWe show the compatibility of these machine-measured fower colour scores with the previously\r\nused manual scores and study impact of external efect on the resulting scores. Finally, we use\r\nthe machine-measured fower colour scores to ft and examine a phenotype cline across the\r\nhybrid zone in Planoles using full fower images as opposed to discrete, manual scores and\r\ncompare it with the genotypic cline." acknowledged_ssus: - _id: ScienComp - _id: Bio alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Lenka full_name: Matejovicova, Lenka id: 2DFDEC72-F248-11E8-B48F-1D18A9856A87 last_name: Matejovicova citation: ama: Matejovicova L. Genetic basis of flower colour as a model for adaptive evolution. 2022. doi:10.15479/at:ista:11128 apa: Matejovicova, L. (2022). Genetic basis of flower colour as a model for adaptive evolution. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:11128 chicago: Matejovicova, Lenka. “Genetic Basis of Flower Colour as a Model for Adaptive Evolution.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:11128. ieee: L. Matejovicova, “Genetic basis of flower colour as a model for adaptive evolution,” Institute of Science and Technology Austria, 2022. ista: Matejovicova L. 2022. Genetic basis of flower colour as a model for adaptive evolution. Institute of Science and Technology Austria. mla: Matejovicova, Lenka. Genetic Basis of Flower Colour as a Model for Adaptive Evolution. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:11128. short: L. Matejovicova, Genetic Basis of Flower Colour as a Model for Adaptive Evolution, Institute of Science and Technology Austria, 2022. corr_author: '1' date_created: 2022-04-07T08:19:54Z date_published: 2022-04-06T00:00:00Z date_updated: 2026-04-07T14:12:19Z day: '06' ddc: - '576' - '582' degree_awarded: PhD department: - _id: GradSch - _id: NiBa doi: 10.15479/at:ista:11128 file: - access_level: open_access checksum: e9609bc4e8f8e20146fc1125fd4f1bf7 content_type: application/pdf creator: cchlebak date_created: 2022-04-07T08:11:34Z date_updated: 2022-04-07T08:11:34Z file_id: '11129' file_name: LenkaPhD_Official_PDFA.pdf file_size: 11906472 relation: main_file - access_level: closed checksum: 99d67040432fd07a225643a212ee8588 content_type: application/x-zip-compressed creator: cchlebak date_created: 2022-04-07T08:11:51Z date_updated: 2022-04-07T08:11:51Z file_id: '11130' file_name: LenkaPhD Official_source.zip file_size: 23036766 relation: source_file file_date_updated: 2022-04-07T08:11:51Z has_accepted_license: '1' language: - iso: eng month: '04' oa: 1 oa_version: Published Version page: '112' publication_identifier: isbn: - 978-3-99078-016-9 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria status: public supervisor: - first_name: Nicholas H full_name: Barton, Nicholas H id: 4880FE40-F248-11E8-B48F-1D18A9856A87 last_name: Barton orcid: 0000-0002-8548-5240 title: Genetic basis of flower colour as a model for adaptive evolution 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) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2022' ... --- OA_place: publisher _id: '12072' abstract: - lang: eng text: "In this thesis, we study two of the most important questions in Arithmetic geometry: that of the existence and density of solutions to Diophantine equations. In order for a Diophantine equation to have any solutions over the rational numbers, it must have solutions everywhere locally, i.e., over R and over Qp for every prime p. The converse, called the Hasse principle, is known to fail in general. However, it is still a central question in Arithmetic geometry to determine for which varieties the Hasse principle does hold. In this work, we establish the Hasse principle for a wide new family of varieties of the form f(t) = NK/Q(x) ̸= 0, where f is a polynomial with integer coefficients and NK/Q denotes the norm\r\nform associated to a number field K. Our results cover products of arbitrarily many linear, quadratic or cubic factors, and generalise an argument of Irving [69], which makes use of the beta sieve of Rosser and Iwaniec. We also demonstrate how our main sieve results can be applied to treat new cases of a conjecture of Harpaz and Wittenberg on locally split values of polynomials over number fields, and discuss consequences for rational points in fibrations.\r\nIn the second question, about the density of solutions, one defines a height function and seeks to estimate asymptotically the number of points of height bounded by B as B → ∞. Traditionally, one either counts rational points, or\r\nintegral points with respect to a suitable model. However, in this thesis, we study an emerging area of interest in Arithmetic geometry known as Campana points, which in some sense interpolate between rational and integral points.\r\nMore precisely, we count the number of nonzero integers z1, z2, z3 such that gcd(z1, z2, z3) = 1, and z1, z2, z3, z1 + z2 + z3 are all squareful and bounded by B. Using the circle method, we obtain an asymptotic formula which agrees in\r\nthe power of B and log B with a bold new generalisation of Manin’s conjecture to the setting of Campana points, recently formulated by Pieropan, Smeets, Tanimoto and Várilly-Alvarado [96]. However, in this thesis we also provide the first known counterexamples to leading constant predicted by their conjecture. " acknowledgement: I acknowledge the received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska Curie Grant Agreement No. 665385. alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Alec L full_name: Shute, Alec L id: 440EB050-F248-11E8-B48F-1D18A9856A87 last_name: Shute orcid: 0000-0002-1812-2810 citation: ama: 'Shute AL. Existence and density problems in Diophantine geometry: From norm forms to Campana points. 2022. doi:10.15479/at:ista:12072' apa: 'Shute, A. L. (2022). Existence and density problems in Diophantine geometry: From norm forms to Campana points. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12072' chicago: 'Shute, Alec L. “Existence and Density Problems in Diophantine Geometry: From Norm Forms to Campana Points.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:12072.' ieee: 'A. L. Shute, “Existence and density problems in Diophantine geometry: From norm forms to Campana points,” Institute of Science and Technology Austria, 2022.' ista: 'Shute AL. 2022. Existence and density problems in Diophantine geometry: From norm forms to Campana points. Institute of Science and Technology Austria.' mla: 'Shute, Alec L. Existence and Density Problems in Diophantine Geometry: From Norm Forms to Campana Points. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:12072.' short: 'A.L. Shute, Existence and Density Problems in Diophantine Geometry: From Norm Forms to Campana Points, Institute of Science and Technology Austria, 2022.' corr_author: '1' date_created: 2022-09-08T21:53:03Z date_published: 2022-09-08T00:00:00Z date_updated: 2026-04-07T14:13:35Z day: '08' ddc: - '512' degree_awarded: PhD department: - _id: GradSch - _id: TiBr doi: 10.15479/at:ista:12072 ec_funded: 1 file: - access_level: open_access checksum: bf073344320e05d92c224786cec2e92d content_type: application/pdf creator: ashute date_created: 2022-09-08T21:50:34Z date_updated: 2022-09-08T21:50:34Z file_id: '12073' file_name: Thesis_final_draft.pdf file_size: 1907386 relation: main_file success: 1 - access_level: closed checksum: b054ac6baa09f70e8235403a4abbed80 content_type: application/octet-stream creator: ashute date_created: 2022-09-08T21:50:42Z date_updated: 2022-09-12T11:24:21Z file_id: '12074' file_name: athesis.tex file_size: 495393 relation: source_file - access_level: closed checksum: 0a31e905f1cff5eb8110978cc90e1e79 content_type: application/x-zip-compressed creator: ashute date_created: 2022-09-09T12:05:00Z date_updated: 2022-09-12T11:24:21Z file_id: '12078' file_name: qfcjsfmtvtbfrjjvhdzrnqxfvgjvxtbf.zip file_size: 944534 relation: source_file file_date_updated: 2022-09-12T11:24:21Z has_accepted_license: '1' language: - iso: eng month: '09' oa: 1 oa_version: Published Version page: '208' project: - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program publication_identifier: isbn: - 978-3-99078-023-7 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '12076' relation: part_of_dissertation status: public - id: '12077' relation: part_of_dissertation status: public status: public supervisor: - first_name: Timothy D full_name: Browning, Timothy D id: 35827D50-F248-11E8-B48F-1D18A9856A87 last_name: Browning orcid: 0000-0002-8314-0177 title: 'Existence and density problems in Diophantine geometry: From norm forms to Campana points' tmp: image: /images/cc_by_nc_sa.png legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) short: CC BY-NC-SA (4.0) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2022' ... --- OA_place: publisher _id: '12368' abstract: - lang: eng text: "Metazoan development relies on the formation and remodeling of cell-cell contacts. The \r\nbinding of adhesion receptors and remodeling of the actomyosin cell cortex at cell-cell \r\ninteraction sites have been implicated in cell-cell contact formation. Yet, how these two \r\nprocesses functionally interact to drive cell-cell contact expansion and strengthening \r\nremains unclear. Here, we study how primary germ layer progenitor cells from zebrafish \r\nbind to supported lipid bilayers (SLB) functionalized with E-cadherin ectodomains as an \r\nassay system for monitoring cell-cell contact formation at high spatiotemporal resolution. \r\nWe show that cell-cell contact formation represents a two-tiered process: E-cadherin\x02mediated downregulation of the small GTPase RhoA at the forming contact leads to both \r\ndepletion of Myosin-2 and decrease of F-actin. This is followed by centrifugal actin \r\nnetwork flows at the contact triggered by a sharp gradient of Myosin-2 at the rim of the \r\ncontact zone, with Myosin-2 displaying higher cortical localization outside than inside of \r\nthe contact. These centrifugal cortical actin flows, in turn, not only further dilute the actin \r\nnetwork at the contact disc, but also lead to an accumulation of both F-actin and E\x02cadherin at the contact rim. Eventually, this combination of actomyosin downregulation \r\nand flows at the contact contribute to the characteristic molecular organization implicated \r\nin contact formation and maintenance: depletion of cortical actomyosin at the contact disc, \r\ndriving contact expansion by lowering interfacial tension at the contact, and accumulation \r\nof both E-cadherin and F-actin at the contact rim, mechanically linking the contractile \r\ncortices of the adhering cells. Thus, using a biomimetic assay, we exemplify how \r\nadhesion signaling and cell mechanics function together to modulate the spatial \r\norganization of cell-cell contacts." acknowledged_ssus: - _id: LifeSc - _id: Bio - _id: NanoFab alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Feyza N full_name: Arslan, Feyza N id: 49DA7910-F248-11E8-B48F-1D18A9856A87 last_name: Arslan orcid: 0000-0001-5809-9566 citation: ama: Arslan FN. Remodeling of E-cadherin-mediated contacts via cortical  flows. 2022. doi:10.15479/at:ista:12153 apa: Arslan, F. N. (2022). Remodeling of E-cadherin-mediated contacts via cortical  flows. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12153 chicago: Arslan, Feyza N. “Remodeling of E-Cadherin-Mediated Contacts via Cortical  Flows.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:12153. ieee: F. N. Arslan, “Remodeling of E-cadherin-mediated contacts via cortical  flows,” Institute of Science and Technology Austria, 2022. ista: Arslan FN. 2022. Remodeling of E-cadherin-mediated contacts via cortical  flows. Institute of Science and Technology Austria. mla: Arslan, Feyza N. Remodeling of E-Cadherin-Mediated Contacts via Cortical  Flows. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:12153. short: F.N. Arslan, Remodeling of E-Cadherin-Mediated Contacts via Cortical  Flows, Institute of Science and Technology Austria, 2022. corr_author: '1' date_created: 2023-01-25T10:43:24Z date_published: 2022-09-29T00:00:00Z date_updated: 2026-04-07T14:13:19Z day: '29' ddc: - '570' degree_awarded: PhD department: - _id: GradSch - _id: CaHe doi: 10.15479/at:ista:12153 ec_funded: 1 file: - access_level: open_access checksum: e54a3e69b83ebf166544164afd25608e content_type: application/pdf creator: cchlebak date_created: 2023-01-25T10:52:46Z date_updated: 2023-01-25T10:52:46Z file_id: '12369' file_name: THESIS_FINAL_FArslan_pdfa.pdf file_size: 14581024 relation: main_file success: 1 file_date_updated: 2023-01-25T10:52:46Z has_accepted_license: '1' language: - iso: eng month: '09' oa: 1 oa_version: Published Version page: '113' project: - _id: 260F1432-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '742573' name: Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation publication_identifier: isbn: - '978-3-99078-025-1 ' issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '9350' relation: part_of_dissertation status: public status: public supervisor: - first_name: Carl-Philipp J full_name: Heisenberg, Carl-Philipp J id: 39427864-F248-11E8-B48F-1D18A9856A87 last_name: Heisenberg orcid: 0000-0002-0912-4566 title: Remodeling of E-cadherin-mediated contacts via cortical flows 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) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2022' ... --- OA_place: publisher _id: '11777' abstract: - lang: eng text: "In this dissertation we study coboundary expansion of simplicial complex with a view of giving geometric applications.\r\nOur main novel tool is an equivariant version of Gromov's celebrated Topological Overlap Theorem. The equivariant topological overlap theorem leads to various geometric applications including a quantitative non-embeddability result for sufficiently thick buildings (which partially resolves a conjecture of Tancer and Vorwerk) and an improved lower bound on the pair-crossing number of (bounded degree) expander graphs. Additionally, we will give new proofs for several known lower bounds for geometric problems such as the number of Tverberg partitions or the crossing number of complete bipartite graphs.\r\nFor the aforementioned applications one is naturally lead to study expansion properties of joins of simplicial complexes. In the presence of a special certificate for expansion (as it is the case, e.g., for spherical buildings), the join of two expanders is an expander. On the flip-side, we report quite some evidence that coboundary expansion exhibits very non-product-like behaviour under taking joins. For instance, we exhibit infinite families of graphs $(G_n)_{n\\in \\mathbb{N}}$ and $(H_n)_{n\\in\\mathbb{N}}$ whose join $G_n*H_n$ has expansion of lower order than the product of the expansion constant of the graphs. Moreover, we show an upper bound of $(d+1)/2^d$ on the normalized coboundary expansion constants for the complete multipartite complex $[n]^{*(d+1)}$ (under a mild divisibility condition on $n$).\r\nVia the probabilistic method the latter result extends to an upper bound of $(d+1)/2^d+\\varepsilon$ on the coboundary expansion constant of the spherical building associated with $\\mathrm{PGL}_{d+2}(\\mathbb{F}_q)$ for any $\\varepsilon>0$ and sufficiently large $q=q(\\varepsilon)$. This disproves a conjecture of Lubotzky, Meshulam and Mozes -- in a rather strong sense.\r\nBy improving on existing lower bounds we make further progress towards closing the gap between the known lower and upper bounds on the coboundary expansion constants of $[n]^{*(d+1)}$. The best improvements we achieve using computer-aided proofs and flag algebras. The exact value even for the complete $3$-partite $2$-dimensional complex $[n]^{*3}$ remains unknown but we are happy to conjecture a precise value for every $n$. %Moreover, we show that a previously shown lower bound on the expansion constant of the spherical building associated with $\\mathrm{PGL}_{2}(\\mathbb{F}_q)$ is not tight.\r\nIn a loosely structured, last chapter of this thesis we collect further smaller observations related to expansion. We point out a link between discrete Morse theory and a technique for showing coboundary expansion, elaborate a bit on the hardness of computing coboundary expansion constants, propose a new criterion for coboundary expansion (in a very dense setting) and give one way of making the folklore result that expansion of links is a necessary condition for a simplicial complex to be an expander precise." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Pascal full_name: Wild, Pascal id: 4C20D868-F248-11E8-B48F-1D18A9856A87 last_name: Wild citation: ama: Wild P. High-dimensional expansion and crossing numbers of simplicial complexes. 2022. doi:10.15479/at:ista:11777 apa: Wild, P. (2022). High-dimensional expansion and crossing numbers of simplicial complexes. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:11777 chicago: Wild, Pascal. “High-Dimensional Expansion and Crossing Numbers of Simplicial Complexes.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:11777. ieee: P. Wild, “High-dimensional expansion and crossing numbers of simplicial complexes,” Institute of Science and Technology Austria, 2022. ista: Wild P. 2022. High-dimensional expansion and crossing numbers of simplicial complexes. Institute of Science and Technology Austria. mla: Wild, Pascal. High-Dimensional Expansion and Crossing Numbers of Simplicial Complexes. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:11777. short: P. Wild, High-Dimensional Expansion and Crossing Numbers of Simplicial Complexes, Institute of Science and Technology Austria, 2022. corr_author: '1' date_created: 2022-08-10T15:51:19Z date_published: 2022-08-11T00:00:00Z date_updated: 2026-04-07T14:18:26Z day: '11' ddc: - '500' - '516' - '514' degree_awarded: PhD department: - _id: GradSch - _id: UlWa doi: 10.15479/at:ista:11777 ec_funded: 1 file: - access_level: open_access checksum: f5f3af1fb7c8a24b71ddc88ad7f7c5b4 content_type: text/x-python creator: pwild date_created: 2022-08-10T15:34:04Z date_updated: 2022-08-10T15:34:04Z description: Code for computer-assisted proofs in Section 8.4.7 in Thesis file_id: '11780' file_name: flags.py file_size: 16828 relation: supplementary_material - access_level: open_access checksum: 1f7c12dfe3bdaa9b147e4fbc3d34e3d5 content_type: text/x-c++src creator: pwild date_created: 2022-08-10T15:34:10Z date_updated: 2022-08-10T15:34:10Z description: Code for proof of Lemma 8.20 in Thesis file_id: '11781' file_name: lowerbound.cpp file_size: 12226 relation: supplementary_material - access_level: open_access checksum: 4cf81455c49e5dec3b9b2e3980137eeb content_type: text/x-python creator: pwild date_created: 2022-08-10T15:34:17Z date_updated: 2022-08-10T15:34:17Z description: Code for proof of Proposition 7.9 in Thesis file_id: '11782' file_name: upperbound.py file_size: 3240 relation: supplementary_material - access_level: open_access checksum: 4e96575b10cbe4e0d0db2045b2847774 content_type: application/pdf creator: pwild date_created: 2022-08-11T16:08:33Z date_updated: 2022-08-11T16:08:33Z file_id: '11809' file_name: finalthesisPascalWildPDFA.pdf file_size: 5086282 relation: main_file title: High-Dimensional Expansion and Crossing Numbers of Simplicial Complexes - access_level: closed checksum: 92d94842a1fb6dca5808448137573b2e content_type: application/zip creator: pwild date_created: 2022-08-11T16:09:19Z date_updated: 2022-08-11T16:09:19Z file_id: '11810' file_name: ThesisSubmission.zip file_size: 18150068 relation: source_file file_date_updated: 2022-08-11T16:09:19Z has_accepted_license: '1' language: - iso: eng month: '08' oa: 1 oa_version: Published Version page: '170' project: - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program publication_identifier: isbn: - 978-3-99078-021-3 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria status: public supervisor: - first_name: Uli full_name: Wagner, Uli id: 36690CA2-F248-11E8-B48F-1D18A9856A87 last_name: Wagner orcid: 0000-0002-1494-0568 title: High-dimensional expansion and crossing numbers of simplicial complexes type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2022' ... --- OA_place: publisher _id: '11473' abstract: - lang: eng text: "The polaron model is a basic model of quantum field theory describing a single particle\r\ninteracting with a bosonic field. It arises in many physical contexts. We are mostly concerned\r\nwith models applicable in the context of an impurity atom in a Bose-Einstein condensate as\r\nwell as the problem of electrons moving in polar crystals.\r\nThe model has a simple structure in which the interaction of the particle with the field is given\r\nby a term linear in the field’s creation and annihilation operators. In this work, we investigate\r\nthe properties of this model by providing rigorous estimates on various energies relevant to the\r\nproblem. The estimates are obtained, for the most part, by suitable operator techniques which\r\nconstitute the principal mathematical substance of the thesis.\r\nThe first application of these techniques is to derive the polaron model rigorously from first\r\nprinciples, i.e., from a full microscopic quantum-mechanical many-body problem involving an\r\nimpurity in an otherwise homogeneous system. We accomplish this for the N + 1 Bose gas\r\nin the mean-field regime by showing that a suitable polaron-type Hamiltonian arises at weak\r\ninteractions as a low-energy effective theory for this problem.\r\nIn the second part, we investigate rigorously the ground state of the model at fixed momentum\r\nand for large values of the coupling constant. Qualitatively, the system is expected to display\r\na transition from the quasi-particle behavior at small momenta, where the dispersion relation\r\nis parabolic and the particle moves through the medium dragging along a cloud of phonons, to\r\nthe radiative behavior at larger momenta where the polaron decelerates and emits free phonons.\r\nAt the same time, in the strong coupling regime, the bosonic field is expected to behave purely\r\nclassically. Accordingly, the effective mass of the polaron at strong coupling is conjectured to\r\nbe asymptotically equal to the one obtained from the semiclassical counterpart of the problem,\r\nfirst studied by Landau and Pekar in the 1940s. For polaron models with regularized form\r\nfactors and phonon dispersion relations of superfluid type, i.e., bounded below by a linear\r\nfunction of the wavenumbers for all phonon momenta as in the interacting Bose gas, we prove\r\nthat for a large window of momenta below the radiation threshold, the energy-momentum\r\nrelation at strong coupling is indeed essentially a parabola with semi-latus rectum equal to the\r\nLandau–Pekar effective mass, as expected.\r\nFor the Fröhlich polaron describing electrons in polar crystals where the dispersion relation is\r\nof the optical type and the form factor is formally UV–singular due to the nature of the point\r\ncharge-dipole interaction, we are able to give the corresponding upper bound. In contrast to\r\nthe regular case, this requires the inclusion of the quantum fluctuations of the phonon field,\r\nwhich makes the problem considerably more difficult.\r\nThe results are supplemented by studies on the absolute ground-state energy at strong coupling,\r\na proof of the divergence of the effective mass with the coupling constant for a wide class of\r\npolaron models, as well as the discussion of the apparent UV singularity of the Fröhlich model\r\nand the application of the techniques used for its removal for the energy estimates.\r\n" acknowledged_ssus: - _id: SSU alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Krzysztof full_name: Mysliwy, Krzysztof id: 316457FC-F248-11E8-B48F-1D18A9856A87 last_name: Mysliwy citation: ama: 'Mysliwy K. Polarons in Bose gases and polar crystals: Some rigorous energy estimates. 2022. doi:10.15479/at:ista:11473' apa: 'Mysliwy, K. (2022). Polarons in Bose gases and polar crystals: Some rigorous energy estimates. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:11473' chicago: 'Mysliwy, Krzysztof. “Polarons in Bose Gases and Polar Crystals: Some Rigorous Energy Estimates.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:11473.' ieee: 'K. Mysliwy, “Polarons in Bose gases and polar crystals: Some rigorous energy estimates,” Institute of Science and Technology Austria, 2022.' ista: 'Mysliwy K. 2022. Polarons in Bose gases and polar crystals: Some rigorous energy estimates. Institute of Science and Technology Austria.' mla: 'Mysliwy, Krzysztof. Polarons in Bose Gases and Polar Crystals: Some Rigorous Energy Estimates. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:11473.' short: 'K. Mysliwy, Polarons in Bose Gases and Polar Crystals: Some Rigorous Energy Estimates, Institute of Science and Technology Austria, 2022.' corr_author: '1' date_created: 2022-06-30T12:15:03Z date_published: 2022-07-01T00:00:00Z date_updated: 2026-04-07T14:14:52Z day: '01' ddc: - '515' - '539' degree_awarded: PhD department: - _id: GradSch - _id: RoSe doi: 10.15479/at:ista:11473 ec_funded: 1 file: - access_level: open_access checksum: 7970714a20a6052f75fb27a6c3e9976e content_type: application/pdf creator: kmysliwy date_created: 2022-07-05T08:12:56Z date_updated: 2022-07-05T08:12:56Z file_id: '11486' file_name: thes1_no_isbn_2_1b.pdf file_size: 1830973 relation: main_file success: 1 - access_level: closed checksum: 647a2011fdf56277096c9350fefe1097 content_type: application/zip creator: kmysliwy date_created: 2022-07-05T08:15:52Z date_updated: 2022-07-05T08:17:12Z file_id: '11487' file_name: thes_source.zip file_size: 5831060 relation: source_file file_date_updated: 2022-07-05T08:17:12Z has_accepted_license: '1' language: - iso: eng month: '07' oa: 1 oa_version: Published Version page: '138' project: - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '10564' relation: part_of_dissertation status: public - id: '8705' relation: part_of_dissertation status: public status: public supervisor: - first_name: Robert full_name: Seiringer, Robert id: 4AFD0470-F248-11E8-B48F-1D18A9856A87 last_name: Seiringer orcid: 0000-0002-6781-0521 title: 'Polarons in Bose gases and polar crystals: Some rigorous energy estimates' type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2022' ... --- OA_place: publisher _id: '11945' abstract: - lang: eng text: "G protein-coupled receptors (GPCRs) respond to specific ligands and regulate multiple processes ranging from cell growth and immune responses to neuronal signal transmission. However, ligands for many GPCRs remain unknown, suffer from off-target effects or have poor bioavailability. Additional challenges exist to dissect cell-type specific responses when the same GPCR is expressed on several cell types within the body. Here, we overcome these limitations by engineering DREADD-based GPCR chimeras that selectively bind their agonist clozapine-N-oxide (CNO) and mimic a GPCR-of-interest in a desired cell type.\r\nWe validated our approach with β2-adrenergic receptor (β2AR/ADRB2) and show that our chimeric DREADD-β2AR triggers comparable responses on second messenger and kinase activity, post-translational modifications, and protein-protein interactions. Since β2AR is also enriched in microglia, which can drive inflammation in the central nervous system, we expressed chimeric DREADD-β2AR in primary microglia and successfully recapitulate β2AR-mediated filopodia formation through CNO stimulation. To dissect the role of selected GPCRs during microglial inflammation, we additionally generated DREADD-based chimeras for microglia-enriched GPR65 and GPR109A/HCAR2. In a microglia cell line, DREADD-β2AR and DREADD-GPR65 both modulated the inflammatory response with a similar profile as endogenously expressed β2AR, while DREADD-GPR109A showed no impact.\r\nOur DREADD-based approach provides the means to obtain mechanistic and functional insights into GPCR signaling on a cell-type specific level." acknowledged_ssus: - _id: Bio - _id: PreCl - _id: LifeSc alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Rouven full_name: Schulz, Rouven id: 4C5E7B96-F248-11E8-B48F-1D18A9856A87 last_name: Schulz orcid: 0000-0001-5297-733X citation: ama: Schulz R. Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function. 2022. doi:10.15479/at:ista:11945 apa: Schulz, R. (2022). Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:11945 chicago: Schulz, Rouven. “Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling Pathways and Modulate Microglia Function.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:11945. ieee: R. Schulz, “Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function,” Institute of Science and Technology Austria, 2022. ista: Schulz R. 2022. Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function. Institute of Science and Technology Austria. mla: Schulz, Rouven. Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling Pathways and Modulate Microglia Function. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:11945. short: R. Schulz, Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling Pathways and Modulate Microglia Function, Institute of Science and Technology Austria, 2022. corr_author: '1' date_created: 2022-08-23T11:33:11Z date_published: 2022-08-23T00:00:00Z date_updated: 2026-04-07T14:17:59Z day: '23' ddc: - '570' degree_awarded: PhD department: - _id: GradSch - _id: SaSi doi: 10.15479/at:ista:11945 file: - access_level: open_access checksum: 61b1b666a210ff7cdd0e95ea75207a13 content_type: application/pdf creator: rschulz date_created: 2022-08-25T08:59:57Z date_updated: 2022-08-25T08:59:57Z file_id: '11970' file_name: Thesis_Rouven_Schulz_2022_final.pdf file_size: 28079331 relation: main_file success: 1 - access_level: closed checksum: 2b8f95ea1c134dbdb927b41b1dbeeeb5 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: rschulz date_created: 2022-08-25T09:00:11Z date_updated: 2022-08-25T09:33:31Z file_id: '11971' file_name: Thesis_Rouven_Schulz_2022_final.docx file_size: 27226963 relation: source_file file_date_updated: 2022-08-25T09:33:31Z has_accepted_license: '1' language: - iso: eng month: '08' oa: 1 oa_version: Published Version page: '133' project: - _id: 267F75D8-B435-11E9-9278-68D0E5697425 name: Modulating microglia through G protein-coupled receptor (GPCR) signaling publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '11995' relation: dissertation_contains status: public status: public supervisor: - first_name: Sandra full_name: Siegert, Sandra id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 title: Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function 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) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2022' ...