[{"_id":"11932","status":"public","type":"dissertation","ddc":["573"],"supervisor":[{"last_name":"Csicsvari","full_name":"Csicsvari, Jozsef L","orcid":"0000-0002-5193-4036","first_name":"Jozsef L","id":"3FA14672-F248-11E8-B48F-1D18A9856A87"}],"date_updated":"2023-09-05T12:02:14Z","department":[{"_id":"GradSch"},{"_id":"JoCs"}],"file_date_updated":"2023-06-20T22:30:04Z","oa_version":"Published Version","abstract":[{"lang":"eng","text":"The ability to form and retrieve memories is central to survival. In mammals, the hippocampus\r\nis a brain region essential to the acquisition and consolidation of new memories. It is also\r\ninvolved in keeping track of one’s position in space and aids navigation. Although this\r\nspace-memory has been a source of contradiction, evidence supports the view that the role of\r\nthe hippocampus in navigation is memory, thanks to the formation of cognitive maps. First\r\nintroduced by Tolman in 1948, cognitive maps are generally used to organize experiences in\r\nmemory; however, the detailed mechanisms by which these maps are formed and stored are not\r\nyet agreed upon. Some influential theories describe this process as involving three fundamental\r\nsteps: initial encoding by the hippocampus, interactions between the hippocampus and other\r\ncortical areas, and long-term extra-hippocampal consolidation. In this thesis, I will show how\r\nthe investigation of cognitive maps of space helped to shed light on each of these three memory\r\nprocesses.\r\nThe first study included in this thesis deals with the initial encoding of spatial memories in\r\nthe hippocampus. Much is known about encoding at the level of single cells, but less about\r\ntheir co-activity or joint contribution to the encoding of novel spatial information. I will\r\ndescribe the structure of an interaction network that allows for efficient encoding of noisy\r\nspatial information during the first exploration of a novel environment.\r\nThe second study describes the interactions between the hippocampus and the prefrontal\r\ncortex (PFC), two areas directly and indirectly connected. It is known that the PFC, in concert\r\nwith the hippocampus, is involved in various processes, including memory storage and spatial\r\nnavigation. Nonetheless, the detailed mechanisms by which PFC receives information from the\r\nhippocampus are not clear. I will show how a transient improvement in theta phase locking of\r\nPFC cells enables interactions of cell pairs across the two regions.\r\nThe third study describes the learning of behaviorally-relevant spatial locations in the hippocampus and the medial entorhinal cortex. I will show how the accumulation of firing around\r\ngoal locations, a correlate of learning, can shed light on the transition from short- to long-term\r\nspatial memories and the speed of consolidation in different brain areas.\r\nThe studies included in this thesis represent the main scientific contributions of my Ph.D. They\r\ninvolve statistical analyses and models of neural responses of cells in different brain areas of\r\nrats executing spatial tasks. I will conclude the thesis by discussing the impact of the findings\r\non principles of memory formation and retention, including the mechanisms, the speed, and\r\nthe duration of these processes."}],"month":"08","alternative_title":["ISTA Thesis"],"file":[{"file_size":13515457,"date_updated":"2023-06-20T22:30:04Z","creator":"mnardin","file_name":"Michele Nardin, Ph.D. Thesis - ISTA (1).zip","date_created":"2022-08-19T16:31:34Z","embargo_to":"open_access","content_type":"application/zip","relation":"source_file","access_level":"closed","checksum":"2dbb70c74aaa3b64c1f463e943baf09c","file_id":"11935"},{"date_updated":"2023-06-20T22:30:04Z","file_size":9906458,"creator":"mnardin","date_created":"2022-08-22T09:43:50Z","file_name":"Michele_Nardin_Phd_Thesis_PDFA.pdf","content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"0ec94035ea35a47a9f589ed168e60b48","file_id":"11941","embargo":"2023-06-19"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2663-337X"]},"degree_awarded":"PhD","publication_status":"published","related_material":{"record":[{"relation":"part_of_dissertation","id":"10077","status":"public"},{"status":"public","id":"6194","relation":"part_of_dissertation"}]},"ec_funded":1,"project":[{"name":"International IST Doctoral Program","grant_number":"665385","call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"}],"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","citation":{"chicago":"Nardin, Michele. “On the Encoding, Transfer, and Consolidation of Spatial Memories.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:11932.","ista":"Nardin M. 2022. On the encoding, transfer, and consolidation of spatial memories. Institute of Science and Technology Austria.","mla":"Nardin, Michele. On the Encoding, Transfer, and Consolidation of Spatial Memories. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:11932.","apa":"Nardin, M. (2022). On the encoding, transfer, and consolidation of spatial memories. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:11932","ama":"Nardin M. On the encoding, transfer, and consolidation of spatial memories. 2022. doi:10.15479/at:ista:11932","ieee":"M. Nardin, “On the encoding, transfer, and consolidation of spatial memories,” Institute of Science and Technology Austria, 2022.","short":"M. Nardin, On the Encoding, Transfer, and Consolidation of Spatial Memories, Institute of Science and Technology Austria, 2022."},"title":"On the encoding, transfer, and consolidation of spatial memories","author":[{"orcid":"0000-0001-8849-6570","full_name":"Nardin, Michele","last_name":"Nardin","first_name":"Michele","id":"30BD0376-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"No","acknowledgement":"I acknowledge the support from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Grant Agreement No. 665385.","publisher":"Institute of Science and Technology Austria","oa":1,"day":"19","has_accepted_license":"1","year":"2022","date_published":"2022-08-19T00:00:00Z","doi":"10.15479/at:ista:11932","date_created":"2022-08-19T08:52:30Z","page":"136"},{"project":[{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"International IST Doctoral Program","grant_number":"665385"}],"title":"MorphOMICs, a tool for mapping microglial morphology, reveals brain region- and sex-dependent phenotypes","article_processing_charge":"No","author":[{"last_name":"Colombo","orcid":"0000-0001-9434-8902","full_name":"Colombo, Gloria","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","first_name":"Gloria"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"ista":"Colombo G. 2022. MorphOMICs, a tool for mapping microglial morphology, reveals brain region- and sex-dependent phenotypes. Institute of Science and Technology Austria.","chicago":"Colombo, Gloria. “MorphOMICs, a Tool for Mapping Microglial Morphology, Reveals Brain Region- and Sex-Dependent Phenotypes.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:12378.","short":"G. Colombo, MorphOMICs, a Tool for Mapping Microglial Morphology, Reveals Brain Region- and Sex-Dependent Phenotypes, Institute of Science and Technology Austria, 2022.","ieee":"G. Colombo, “MorphOMICs, a tool for mapping microglial morphology, reveals brain region- and sex-dependent phenotypes,” Institute of Science and Technology Austria, 2022.","apa":"Colombo, G. (2022). MorphOMICs, a tool for mapping microglial morphology, reveals brain region- and sex-dependent phenotypes. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12378","ama":"Colombo G. MorphOMICs, a tool for mapping microglial morphology, reveals brain region- and sex-dependent phenotypes. 2022. doi:10.15479/at:ista:12378","mla":"Colombo, Gloria. MorphOMICs, a Tool for Mapping Microglial Morphology, Reveals Brain Region- and Sex-Dependent Phenotypes. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:12378."},"oa":1,"publisher":"Institute of Science and Technology Austria","date_created":"2023-01-25T14:27:43Z","doi":"10.15479/at:ista:12378","date_published":"2022-11-11T00:00:00Z","page":"142","day":"11","year":"2022","has_accepted_license":"1","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"dissertation","_id":"12378","department":[{"_id":"GradSch"},{"_id":"SaSi"}],"file_date_updated":"2023-04-12T22:30:03Z","ddc":["570"],"date_updated":"2023-08-04T09:40:37Z","supervisor":[{"orcid":"0000-0001-8635-0877","full_name":"Siegert, Sandra","last_name":"Siegert","first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"}],"month":"11","alternative_title":["ISTA Thesis"],"oa_version":"Published Version","abstract":[{"text":"Environmental cues influence the highly dynamic morphology of microglia. Strategies to \r\ncharacterize these changes usually involve user-selected morphometric features, which \r\npreclude the identification of a spectrum of context-dependent morphological phenotypes. \r\nHere, we develop MorphOMICs, a topological data analysis approach, which enables semi\u0002automatic mapping of microglial morphology into an atlas of cue-dependent phenotypes,\r\novercomes feature-selection bias and minimizes biological variability. \r\nFirst, with MorphOMICs we derive the morphological spectrum of microglia across seven \r\nbrain regions during postnatal development and in two distinct Alzheimer’s disease \r\ndegeneration mouse models. We uncover region-specific and sexually dimorphic\r\nmorphological trajectories, with females showing an earlier morphological shift than males in \r\nthe degenerating brain. Overall, we demonstrate that both long primary- and short terminal \r\nprocesses provide distinct insights to morphological phenotypes. Moreover, using machine \r\nlearning to map novel condition on the spectrum, we observe that microglia morphologies \r\nreflect a dose-dependent adaptation upon ketamine anesthesia and do not recover to control \r\nmorphologies.\r\nNext, we took advantage of MorphOMICs to build a high-resolution and layer-specific map of \r\nmicroglial morphological spectrum in the retina, covering postnatal development and rd10 \r\ndegeneration. Here, following photoreceptor death, microglia assume an early development\u0002like morphology. Finally, we map microglial morphology following optic nerve crush on the \r\nretinal spectrum and observe a layer- and sex-dependent response. \r\nOverall, MorphOMICs opens a new perspective to analyze microglial morphology across \r\nmultiple conditions, and provides a novel tool to characterize microglial morphology beyond \r\nthe traditionally dichotomized view of microglia.","lang":"eng"}],"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"ScienComp"}],"ec_funded":1,"related_material":{"record":[{"id":"12244","status":"public","relation":"part_of_dissertation"}]},"language":[{"iso":"eng"}],"file":[{"file_size":23890382,"date_updated":"2023-04-12T22:30:03Z","creator":"cchlebak","file_name":"Gloria_Colombo_Thesis.docx","date_created":"2023-01-25T14:31:32Z","embargo_to":"open_access","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","relation":"source_file","access_level":"closed","checksum":"8cd3ddfe9b53381dcf086023d8d8893a","file_id":"12379"},{"creator":"cchlebak","date_updated":"2023-04-12T22:30:03Z","file_size":13802421,"date_created":"2023-01-25T14:31:36Z","file_name":"Gloria_Colombo_Thesis.pdf","access_level":"open_access","relation":"main_file","content_type":"application/pdf","file_id":"12380","checksum":"8af4319c18b516e8758e9a6cb02b103b","embargo":"2023-04-11"}],"degree_awarded":"PhD","publication_status":"published","publication_identifier":{"issn":["2663-337X"]}},{"has_accepted_license":"1","year":"2022","day":"18","page":"98","date_published":"2022-05-18T00:00:00Z","doi":"10.15479/at:ista:11388","date_created":"2022-05-16T16:49:18Z","publisher":"Institute of Science and Technology Austria","oa":1,"citation":{"ama":"Belohlavy S. The genetic basis of complex traits studied via analysis of evolve and resequence experiments. 2022. doi:10.15479/at:ista:11388","apa":"Belohlavy, S. (2022). The genetic basis of complex traits studied via analysis of evolve and resequence experiments. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:11388","ieee":"S. Belohlavy, “The genetic basis of complex traits studied via analysis of evolve and resequence experiments,” Institute of Science and Technology Austria, 2022.","short":"S. Belohlavy, The Genetic Basis of Complex Traits Studied via Analysis of Evolve and Resequence Experiments, Institute of Science and Technology Austria, 2022.","mla":"Belohlavy, Stefanie. The Genetic Basis of Complex Traits Studied via Analysis of Evolve and Resequence Experiments. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:11388.","ista":"Belohlavy S. 2022. The genetic basis of complex traits studied via analysis of evolve and resequence experiments. Institute of Science and Technology Austria.","chicago":"Belohlavy, Stefanie. “The Genetic Basis of Complex Traits Studied via Analysis of Evolve and Resequence Experiments.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:11388."},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","author":[{"id":"43FE426A-F248-11E8-B48F-1D18A9856A87","first_name":"Stefanie","orcid":"0000-0002-9849-498X","full_name":"Belohlavy, Stefanie","last_name":"Belohlavy"}],"article_processing_charge":"No","title":"The genetic basis of complex traits studied via analysis of evolve and resequence experiments","publication_identifier":{"isbn":["978-3-99078-018-3"]},"publication_status":"published","degree_awarded":"PhD","file":[{"date_created":"2022-05-19T13:03:13Z","file_name":"thesis_sb_final_pdfa.pdf","creator":"sbelohla","date_updated":"2023-05-20T22:30:03Z","file_size":8247240,"checksum":"4d75e6a619df7e8a9d6e840aee182380","file_id":"11398","embargo":"2023-05-19","access_level":"open_access","relation":"main_file","content_type":"application/pdf"},{"relation":"source_file","access_level":"closed","embargo_to":"open_access","content_type":"application/x-zip-compressed","checksum":"7a5d8b6dd0ca00784f860075b0a7d8f0","file_id":"11399","creator":"sbelohla","file_size":7094,"date_updated":"2023-05-20T22:30:03Z","file_name":"thesis_sb_final.zip","date_created":"2022-05-19T13:07:47Z"}],"language":[{"iso":"eng"}],"related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"6713"}]},"abstract":[{"lang":"eng","text":"In evolve and resequence experiments, a population is sequenced, subjected to selection and\r\nthen sequenced again, so that genetic changes before and after selection can be observed at\r\nthe genetic level. Here, I use these studies to better understand the genetic basis of complex\r\ntraits - traits which depend on more than a few genes.\r\nIn the first chapter, I discuss the first evolve and resequence experiment, in which a population\r\nof mice, the so-called \"Longshanks\" mice, were selected for tibia length while their body mass\r\nwas kept constant. The full pedigree is known. We observed a selection response on all\r\nchromosomes and used the infinitesimal model with linkage, a model which assumes an infinite\r\nnumber of genes with infinitesimally small effect sizes, as a null model. Results implied a very\r\npolygenic basis with a few loci of major effect standing out and changing in parallel. There\r\nwas large variability between the different chromosomes in this study, probably due to LD.\r\nIn chapter two, I go on to discuss the impact of LD, on the variability in an allele-frequency\r\nbased summary statistic, giving an equation based on the initial allele frequencies, average\r\npairwise LD, and the first four moments of the haplotype block copy number distribution. I\r\ndescribe this distribution by referring back to the founder generation. I then demonstrate\r\nhow to infer selection via a maximum likelihood scheme on the example of a single locus and\r\ndiscuss how to extend this to more realistic scenarios.\r\nIn chapter three, I discuss the second evolve and resequence experiment, in which a small\r\npopulation of Drosophila melanogaster was selected for increased pupal case size over 6\r\ngenerations. The experiment was highly replicated with 27 lines selected within family and a\r\nknown pedigree. We observed a phenotypic selection response of over one standard deviation.\r\nI describe the patterns in allele frequency data, including allele frequency changes and patterns\r\nof heterozygosity, and give ideas for future work."}],"oa_version":"Published Version","alternative_title":["ISTA Thesis"],"month":"05","supervisor":[{"first_name":"Nicholas H","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8548-5240","full_name":"Barton, Nicholas H","last_name":"Barton"}],"date_updated":"2023-08-29T06:41:51Z","ddc":["576"],"department":[{"_id":"GradSch"},{"_id":"NiBa"}],"file_date_updated":"2023-05-20T22:30:03Z","_id":"11388","type":"dissertation","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public"},{"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","citation":{"chicago":"Tasciyan, Saren. “Role of Microenvironment Heterogeneity in Cancer Cell Invasion.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:12401.","ista":"Tasciyan S. 2022. Role of microenvironment heterogeneity in cancer cell invasion. Institute of Science and Technology Austria.","mla":"Tasciyan, Saren. Role of Microenvironment Heterogeneity in Cancer Cell Invasion. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:12401.","apa":"Tasciyan, S. (2022). Role of microenvironment heterogeneity in cancer cell invasion. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12401","ama":"Tasciyan S. Role of microenvironment heterogeneity in cancer cell invasion. 2022. doi:10.15479/at:ista:12401","short":"S. Tasciyan, Role of Microenvironment Heterogeneity in Cancer Cell Invasion, Institute of Science and Technology Austria, 2022.","ieee":"S. Tasciyan, “Role of microenvironment heterogeneity in cancer cell invasion,” Institute of Science and Technology Austria, 2022."},"title":"Role of microenvironment heterogeneity in cancer cell invasion","article_processing_charge":"No","author":[{"first_name":"Saren","id":"4323B49C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1671-393X","full_name":"Tasciyan, Saren","last_name":"Tasciyan"}],"oa":1,"publisher":"Institute of Science and Technology Austria","day":"22","year":"2022","has_accepted_license":"1","date_created":"2023-01-26T11:55:16Z","doi":"10.15479/at:ista:12401","date_published":"2022-12-22T00:00:00Z","page":"105","_id":"12401","status":"public","type":"dissertation","ddc":["610"],"date_updated":"2023-12-21T23:30:04Z","supervisor":[{"full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","last_name":"Sixt","first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"}],"file_date_updated":"2023-12-21T23:30:03Z","department":[{"_id":"GradSch"},{"_id":"MiSi"}],"oa_version":"Published Version","abstract":[{"text":"Detachment of the cancer cells from the bulk of the tumor is the first step of metastasis, which\r\nis the primary cause of cancer related deaths. It is unclear, which factors contribute to this step.\r\nRecent studies indicate a crucial role of the tumor microenvironment in malignant\r\ntransformation and metastasis. Studying cancer cell invasion and detachments quantitatively in\r\nthe context of its physiological microenvironment is technically challenging. Especially, precise\r\ncontrol of microenvironmental properties in vivo is currently not possible. Here, I studied the\r\nrole of microenvironment geometry in the invasion and detachment of cancer cells from the\r\nbulk with a simplistic and reductionist approach. In this approach, I engineered microfluidic\r\ndevices to mimic a pseudo 3D extracellular matrix environment, where I was able to\r\nquantitatively tune the geometrical configuration of the microenvironment and follow tumor\r\ncells with fluorescence live imaging. To aid quantitative analysis I developed a widely applicable\r\nsoftware application to automatically analyze and visualize particle tracking data.\r\nQuantitative analysis of tumor cell invasion in isotropic and anisotropic microenvironments\r\nshowed that heterogeneity in the microenvironment promotes faster invasion and more\r\nfrequent detachment of cells. These observations correlated with overall higher speed of cells at\r\nthe edge of the bulk of the cells. In heterogeneous microenvironments cells preferentially\r\npassed through larger pores, thus invading areas of least resistance and generating finger-like\r\ninvasive structures. The detachments occurred mostly at the tips of these structures.\r\nTo investigate the potential mechanism, we established a two dimensional model to simulate\r\nactive Brownian particles representing the cell nuclei dynamics. These simulations backed our in\r\nvitro observations without the need of precise fitting the simulation parameters. Our model\r\nsuggests the importance of the pore heterogeneity in the direction perpendicular to the\r\norientation of bias field (lateral heterogeneity), which causes the interface roughening.","lang":"eng"}],"month":"12","alternative_title":["ISTA Thesis"],"language":[{"iso":"eng"}],"file":[{"creator":"cchlebak","date_updated":"2023-12-21T23:30:03Z","file_size":42059787,"date_created":"2023-01-26T11:58:14Z","file_name":"PhD-Thesis_Saren Tasciyan_formatted_aftercrash_fixed_600dpi_95pc_final_PDFA3b.pdf","access_level":"open_access","relation":"main_file","content_type":"application/pdf","file_id":"12402","checksum":"cc4a2b4a7e3c4ee8ef7f2dbf909b12bd","embargo":"2023-12-20"},{"date_updated":"2023-12-21T23:30:03Z","file_size":261256696,"creator":"cchlebak","date_created":"2023-01-26T12:00:10Z","file_name":"Source Files - Saren Tasciyan - PhD Thesis.zip","content_type":"application/x-zip-compressed","embargo_to":"open_access","access_level":"closed","relation":"source_file","file_id":"12403","checksum":"f1b4ca98b8ab0cb043b1830971e9bd9c"}],"publication_status":"published","degree_awarded":"PhD","publication_identifier":{"issn":["2663-337X"]},"related_material":{"record":[{"id":"679","status":"public","relation":"part_of_dissertation"},{"status":"public","id":"10703","relation":"part_of_dissertation"},{"relation":"part_of_dissertation","status":"public","id":"9429"},{"id":"7885","status":"public","relation":"part_of_dissertation"}]}},{"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","citation":{"chicago":"Wachner, Stephanie. “Transcriptional Regulation by Dfos and BMP-Signaling Support Tissue Invasion of Drosophila Immune Cells.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:11193.","ista":"Wachner S. 2022. Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells. Institute of Science and Technology Austria.","mla":"Wachner, Stephanie. Transcriptional Regulation by Dfos and BMP-Signaling Support Tissue Invasion of Drosophila Immune Cells. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:11193.","ama":"Wachner S. Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells. 2022. doi:10.15479/at:ista:11193","apa":"Wachner, S. (2022). Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:11193","ieee":"S. Wachner, “Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells,” Institute of Science and Technology Austria, 2022.","short":"S. Wachner, Transcriptional Regulation by Dfos and BMP-Signaling Support Tissue Invasion of Drosophila Immune Cells, Institute of Science and Technology Austria, 2022."},"title":"Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells","author":[{"full_name":"Wachner, Stephanie","last_name":"Wachner","first_name":"Stephanie","id":"2A95E7B0-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"No","project":[{"_id":"26199CA4-B435-11E9-9278-68D0E5697425","name":"Tissue barrier penetration is crucial for immunity and metastasis","grant_number":"24800"}],"day":"20","has_accepted_license":"1","year":"2022","date_published":"2022-04-20T00:00:00Z","doi":"10.15479/at:ista:11193","date_created":"2022-04-20T08:59:07Z","page":"170","publisher":"Institute of Science and Technology Austria","oa":1,"ddc":["570"],"supervisor":[{"first_name":"Daria E","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","last_name":"Siekhaus","full_name":"Siekhaus, Daria E","orcid":"0000-0001-8323-8353"}],"date_updated":"2023-09-19T10:15:54Z","department":[{"_id":"GradSch"},{"_id":"DaSi"}],"file_date_updated":"2023-04-21T22:30:03Z","_id":"11193","status":"public","type":"dissertation","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"file":[{"file_id":"11195","checksum":"999ab16884c4522486136ebc5ae8dbff","embargo":"2023-04-20","access_level":"open_access","relation":"main_file","content_type":"application/pdf","date_created":"2022-04-20T09:03:57Z","file_name":"Thesis_Stephanie_Wachner_20200414_formatted.pdf","creator":"cchlebak","date_updated":"2023-04-21T22:30:03Z","file_size":8820951},{"creator":"cchlebak","file_size":65864612,"date_updated":"2023-04-21T22:30:03Z","file_name":"Thesis_Stephanie_Wachner_20200414.zip","date_created":"2022-04-22T12:41:00Z","relation":"source_file","access_level":"closed","embargo_to":"open_access","content_type":"application/x-zip-compressed","file_id":"11329","checksum":"fd92b1e38d53bdf8b458213882d41383"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2663-337X"]},"degree_awarded":"PhD","publication_status":"published","related_material":{"record":[{"relation":"part_of_dissertation","id":"10614","status":"public"},{"id":"544","status":"public","relation":"part_of_dissertation"}]},"oa_version":"Published Version","abstract":[{"text":"The infiltration of immune cells into tissues underlies the establishment of tissue-resident\r\nmacrophages and responses to infections and tumors. However, the mechanisms immune\r\ncells utilize to collectively migrate through tissue barriers in vivo are not yet well understood.\r\nIn this thesis, I describe two mechanisms that Drosophila immune cells (hemocytes) use to\r\novercome the tissue barrier of the germband in the embryo. One strategy is the strengthening\r\nof the actin cortex through developmentally controlled transcriptional regulation induced by\r\nthe Drosophila proto-oncogene family member Dfos, which I show in Chapter 2. Dfos induces\r\nexpression of the tetraspanin TM4SF and the filamin Cher leading to higher levels of the\r\nactivated formin Dia at the cortex and increased cortical F-actin. This enhanced cortical\r\nstrength allows hemocytes to overcome the physical resistance of the surrounding tissue and\r\ntranslocate their nucleus to move forward. This mechanism affects the speed of migration\r\nwhen hemocytes face a confined environment in vivo.\r\nAnother aspect of the invasion process is the initial step of the leading hemocytes entering\r\nthe tissue, which potentially guides the follower cells. In Chapter 3, I describe a novel\r\nsubpopulation of hemocytes activated by BMP signaling prior to tissue invasion that leads\r\npenetration into the germband. Hemocytes that are deficient in BMP signaling activation\r\nshow impaired persistence at the tissue entry, while their migration speed remains\r\nunaffected.\r\nThis suggests that there might be different mechanisms controlling immune cell migration\r\nwithin the confined environment in vivo, one of these being the general ability to overcome\r\nthe resistance of the surrounding tissue and another affecting the order of hemocytes that\r\ncollectively invade the tissue in a stream of individual cells.\r\nTogether, my findings provide deeper insights into transcriptional changes in immune\r\ncells that enable efficient tissue invasion and pave the way for future studies investigating the\r\nearly colonization of tissues by macrophages in higher organisms. Moreover, they extend the\r\ncurrent view of Drosophila immune cell heterogeneity and point toward a potentially\r\nconserved role for canonical BMP signaling in specifying immune cells that lead the migration\r\nof tissue resident macrophages during embryogenesis.","lang":"eng"}],"acknowledged_ssus":[{"_id":"LifeSc"}],"month":"04","alternative_title":["ISTA Thesis"]}]