[{"oa_version":"Published Version","abstract":[{"lang":"eng","text":"The process of detecting and evaluating sensory information to guide behaviour is termed perceptual decision-making (PDM), and is critical for the ability of an organism to interact with its external world. Individuals with autism, a neurodevelopmental condition primarily characterised by social and communication difficulties, frequently exhibit altered sensory processing and PDM difficulties are widely reported. Recent technological advancements have pushed forward our understanding of the genetic changes accompanying this condition, however our understanding of how these mutations affect the function of specific neuronal circuits and bring about the corresponding behavioural changes remains limited. Here, we use an innate PDM task, the looming avoidance response (LAR) paradigm, to identify a convergent behavioural abnormality across three molecularly distinct genetic mouse models of autism (Cul3, Setd5 and Ptchd1). Although mutant mice can rapidly detect threatening visual stimuli, their responses are consistently delayed, requiring longer to initiate an appropriate response than their wild-type siblings. Mutant animals show abnormal adaptation in both their stimulus- evoked escape responses and exploratory dynamics following repeated stimulus presentations. Similarly delayed behavioural responses are observed in wild-type animals when faced with more ambiguous threats, suggesting the mutant phenotype could arise from a dysfunction in the flexible control of this PDM process.\r\nOur knowledge of the core neuronal circuitry mediating the LAR facilitated a detailed dissection of the neuronal mechanisms underlying the behavioural impairment. In vivo extracellular recording revealed that visual responses were unaffected within a key brain region for the rapid processing of visual threats, the superior colliculus (SC), indicating that the behavioural delay was unlikely to originate from sensory impairments. Delayed behavioural responses were recapitulated in the Setd5 model following optogenetic stimulation of the excitatory output neurons of the SC, which are known to mediate escape initiation through the activation of cells in the underlying dorsal periaqueductal grey (dPAG). In vitro patch-clamp recordings of dPAG cells uncovered a stark hypoexcitability phenotype in two out of the three genetic models investigated (Setd5 and Ptchd1), that in Setd5, is mediated by the misregulation of voltage-gated potassium channels. Overall, our results show that the ability to use visual information to drive efficient escape responses is impaired in three diverse genetic mouse models of autism and that, in one of the models studied, this behavioural delay likely originates from differences in the intrinsic excitability of a key subcortical node, the dPAG. Furthermore, this work showcases the use of an innate behavioural paradigm to mechanistically dissect PDM processes in autism."}],"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"CampIT"}],"month":"03","alternative_title":["ISTA Thesis"],"language":[{"iso":"eng"}],"file":[{"file_id":"12717","checksum":"6c6d9cc2c4cdacb74e6b1047a34d7332","relation":"source_file","access_level":"closed","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_name":"Burnett_Thesis_2023.docx","date_created":"2023-03-08T15:08:46Z","creator":"lburnett","file_size":23029260,"date_updated":"2023-03-08T15:08:46Z"},{"file_name":"Burnett_Thesis_2023_pdfA.pdf","date_created":"2023-03-08T15:08:46Z","creator":"lburnett","file_size":11959869,"date_updated":"2023-03-08T15:08:46Z","success":1,"file_id":"12718","checksum":"cebc77705288bf4382db9b3541483cd0","relation":"main_file","access_level":"open_access","content_type":"application/pdf"}],"publication_status":"published","degree_awarded":"PhD","publication_identifier":{"issn":["2663-337X"]},"ec_funded":1,"_id":"12716","status":"public","type":"dissertation","ddc":["599","573"],"date_updated":"2023-04-05T10:59:04Z","supervisor":[{"last_name":"Jösch","full_name":"Jösch, Maximilian A","orcid":"0000-0002-3937-1330","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87","first_name":"Maximilian A"}],"department":[{"_id":"GradSch"},{"_id":"MaJö"}],"file_date_updated":"2023-03-08T15:08:46Z","oa":1,"publisher":"Institute of Science and Technology Austria","day":"10","year":"2023","has_accepted_license":"1","date_created":"2023-03-08T15:19:45Z","date_published":"2023-03-10T00:00:00Z","doi":"10.15479/at:ista:12716","page":"178","project":[{"call_identifier":"H2020","_id":"2634E9D2-B435-11E9-9278-68D0E5697425","name":"Circuits of Visual Attention","grant_number":"756502"}],"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","citation":{"ieee":"L. Burnett, “To flee, or not to flee? Using innate defensive behaviours to investigate rapid perceptual decision-making through subcortical circuits in mouse models of autism,” Institute of Science and Technology Austria, 2023.","short":"L. Burnett, To Flee, or Not to Flee? Using Innate Defensive Behaviours to Investigate Rapid Perceptual Decision-Making through Subcortical Circuits in Mouse Models of Autism, Institute of Science and Technology Austria, 2023.","ama":"Burnett L. To flee, or not to flee? Using innate defensive behaviours to investigate rapid perceptual decision-making through subcortical circuits in mouse models of autism. 2023. doi:10.15479/at:ista:12716","apa":"Burnett, L. (2023). To flee, or not to flee? Using innate defensive behaviours to investigate rapid perceptual decision-making through subcortical circuits in mouse models of autism. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12716","mla":"Burnett, Laura. To Flee, or Not to Flee? Using Innate Defensive Behaviours to Investigate Rapid Perceptual Decision-Making through Subcortical Circuits in Mouse Models of Autism. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:12716.","ista":"Burnett L. 2023. To flee, or not to flee? Using innate defensive behaviours to investigate rapid perceptual decision-making through subcortical circuits in mouse models of autism. Institute of Science and Technology Austria.","chicago":"Burnett, Laura. “To Flee, or Not to Flee? Using Innate Defensive Behaviours to Investigate Rapid Perceptual Decision-Making through Subcortical Circuits in Mouse Models of Autism.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:12716."},"title":"To flee, or not to flee? Using innate defensive behaviours to investigate rapid perceptual decision-making through subcortical circuits in mouse models of autism","article_processing_charge":"No","author":[{"last_name":"Burnett","orcid":"0000-0002-8937-410X","full_name":"Burnett, Laura","id":"3B717F68-F248-11E8-B48F-1D18A9856A87","first_name":"Laura"}]},{"project":[{"_id":"238A0A5A-32DE-11EA-91FC-C7463DDC885E","grant_number":"25541","name":"Structural characterization of E. coli complex I: an important mechanistic model"},{"grant_number":"101020697","name":"Structure and mechanism of respiratory chain molecular machines","call_identifier":"H2020","_id":"627abdeb-2b32-11ec-9570-ec31a97243d3"}],"title":"Structural and mechanistic study of bacterial complex I and its cyanobacterial ortholog","author":[{"first_name":"Vladyslav","id":"4D62F2A6-F248-11E8-B48F-1D18A9856A87","last_name":"Kravchuk","full_name":"Kravchuk, Vladyslav"}],"article_processing_charge":"No","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","citation":{"ista":"Kravchuk V. 2023. Structural and mechanistic study of bacterial complex I and its cyanobacterial ortholog. Institute of Science and Technology Austria.","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.","short":"V. Kravchuk, Structural and Mechanistic Study of Bacterial Complex I and Its Cyanobacterial Ortholog, Institute of Science and Technology Austria, 2023.","ieee":"V. Kravchuk, “Structural and mechanistic study of bacterial complex I and its cyanobacterial ortholog,” Institute of Science and Technology Austria, 2023.","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","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."},"publisher":"Institute of Science and Technology Austria","doi":"10.15479/at:ista:12781","date_published":"2023-03-23T00:00:00Z","date_created":"2023-03-31T12:24:42Z","page":"127","day":"23","has_accepted_license":"1","year":"2023","status":"public","type":"dissertation","_id":"12781","department":[{"_id":"GradSch"},{"_id":"LeSa"}],"file_date_updated":"2023-04-20T07:02:59Z","ddc":["570","572"],"supervisor":[{"last_name":"Sazanov","full_name":"Sazanov, Leonid A","orcid":"0000-0002-0977-7989","first_name":"Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87"}],"date_updated":"2023-08-04T08:54:51Z","month":"03","alternative_title":["ISTA Thesis"],"oa_version":"Published Version","abstract":[{"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","lang":"eng"}],"acknowledged_ssus":[{"_id":"EM-Fac"}],"related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"12138"}]},"ec_funded":1,"file":[{"date_created":"2023-04-19T14:33:41Z","file_name":"VladyslavKravchuk_PhD_Thesis_PostSub_Final_1.pdf","creator":"vkravchu","date_updated":"2023-04-19T14:33:41Z","file_size":6071553,"checksum":"5ebb6345cb4119f93460c81310265a6d","file_id":"12852","embargo":"2024-04-20","access_level":"closed","relation":"main_file","content_type":"application/pdf","embargo_to":"local"},{"embargo":"2024-04-20","file_id":"12853","checksum":"c12055c48411d030d2afa51de2166221","embargo_to":"local","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","relation":"source_file","access_level":"closed","file_name":"VladyslavKravchuk_PhD_Thesis_PostSub_Final.docx","date_created":"2023-04-19T14:33:52Z","file_size":19468766,"date_updated":"2023-04-20T07:02:59Z","creator":"vkravchu"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2663-337X"],"isbn":["978-3-99078-029-9"]},"publication_status":"published","degree_awarded":"PhD"},{"author":[{"last_name":"Peste","full_name":"Peste, Elena-Alexandra","first_name":"Elena-Alexandra","id":"32D78294-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"No","title":"Efficiency and generalization of sparse neural networks","citation":{"mla":"Peste, Elena-Alexandra. Efficiency and Generalization of Sparse Neural Networks. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:13074.","ama":"Peste E-A. Efficiency and generalization of sparse neural networks. 2023. doi:10.15479/at:ista:13074","apa":"Peste, E.-A. (2023). Efficiency and generalization of sparse neural networks. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:13074","ieee":"E.-A. Peste, “Efficiency and generalization of sparse neural networks,” Institute of Science and Technology Austria, 2023.","short":"E.-A. Peste, Efficiency and Generalization of Sparse Neural Networks, Institute of Science and Technology Austria, 2023.","chicago":"Peste, Elena-Alexandra. “Efficiency and Generalization of Sparse Neural Networks.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:13074.","ista":"Peste E-A. 2023. Efficiency and generalization of sparse neural networks. Institute of Science and Technology Austria."},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","project":[{"grant_number":"665385","name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"grant_number":"805223","name":"Elastic Coordination for Scalable Machine Learning","call_identifier":"H2020","_id":"268A44D6-B435-11E9-9278-68D0E5697425"}],"page":"147","date_published":"2023-05-23T00:00:00Z","doi":"10.15479/at:ista:13074","date_created":"2023-05-23T17:07:53Z","has_accepted_license":"1","year":"2023","day":"23","publisher":"Institute of Science and Technology Austria","oa":1,"department":[{"_id":"GradSch"},{"_id":"DaAl"},{"_id":"ChLa"}],"file_date_updated":"2023-05-24T16:12:59Z","supervisor":[{"last_name":"Lampert","orcid":"0000-0001-8622-7887","full_name":"Lampert, Christoph","first_name":"Christoph","id":"40C20FD2-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Dan-Adrian","id":"4A899BFC-F248-11E8-B48F-1D18A9856A87","last_name":"Alistarh","full_name":"Alistarh, Dan-Adrian","orcid":"0000-0003-3650-940X"}],"date_updated":"2023-08-04T10:33:27Z","ddc":["000"],"type":"dissertation","status":"public","_id":"13074","related_material":{"record":[{"relation":"part_of_dissertation","id":"11458","status":"public"},{"relation":"part_of_dissertation","id":"13053","status":"public"},{"relation":"part_of_dissertation","id":"12299","status":"public"}]},"ec_funded":1,"publication_identifier":{"issn":["2663-337X"]},"degree_awarded":"PhD","publication_status":"published","file":[{"checksum":"6b3354968403cb9d48cc5a83611fb571","file_id":"13087","success":1,"access_level":"open_access","relation":"main_file","content_type":"application/pdf","date_created":"2023-05-24T16:11:16Z","file_name":"PhD_Thesis_Alexandra_Peste_final.pdf","creator":"epeste","date_updated":"2023-05-24T16:11:16Z","file_size":2152072},{"file_id":"13088","checksum":"8d0df94bbcf4db72c991f22503b3fd60","content_type":"application/zip","access_level":"closed","relation":"source_file","date_created":"2023-05-24T16:12:59Z","file_name":"PhD_Thesis_APeste.zip","date_updated":"2023-05-24T16:12:59Z","file_size":1658293,"creator":"epeste"}],"language":[{"iso":"eng"}],"alternative_title":["ISTA Thesis"],"month":"05","abstract":[{"text":"Deep learning has become an integral part of a large number of important applications, and many of the recent breakthroughs have been enabled by the ability to train very large models, capable to capture complex patterns and relationships from the data. At the same time, the massive sizes of modern deep learning models have made their deployment to smaller devices more challenging; this is particularly important, as in many applications the users rely on accurate deep learning predictions, but they only have access to devices with limited memory and compute power. One solution to this problem is to prune neural networks, by setting as many of their parameters as possible to zero, to obtain accurate sparse models with lower memory footprint. Despite the great research progress in obtaining sparse models that preserve accuracy, while satisfying memory and computational constraints, there are still many challenges associated with efficiently training sparse models, as well as understanding their generalization properties.\r\n\r\nThe focus of this thesis is to investigate how the training process of sparse models can be made more efficient, and to understand the differences between sparse and dense models in terms of how well they can generalize to changes in the data distribution. We first study a method for co-training sparse and dense models, at a lower cost compared to regular training. With our method we can obtain very accurate sparse networks, and dense models that can recover the baseline accuracy. Furthermore, we are able to more easily analyze the differences, at prediction level, between the sparse-dense model pairs. Next, we investigate the generalization properties of sparse neural networks in more detail, by studying how well different sparse models trained on a larger task can adapt to smaller, more specialized tasks, in a transfer learning scenario. Our analysis across multiple pruning methods and sparsity levels reveals that sparse models provide features that can transfer similarly to or better than the dense baseline. However, the choice of the pruning method plays an important role, and can influence the results when the features are fixed (linear finetuning), or when they are allowed to adapt to the new task (full finetuning). Using sparse models with fixed masks for finetuning on new tasks has an important practical advantage, as it enables training neural networks on smaller devices. However, one drawback of current pruning methods is that the entire training cycle has to be repeated to obtain the initial sparse model, for every sparsity target; in consequence, the entire training process is costly and also multiple models need to be stored. In the last part of the thesis we propose a method that can train accurate dense models that are compressible in a single step, to multiple sparsity levels, without additional finetuning. Our method results in sparse models that can be competitive with existing pruning methods, and which can also successfully generalize to new tasks.","lang":"eng"}],"acknowledged_ssus":[{"_id":"ScienComp"}],"oa_version":"Published Version"},{"project":[{"grant_number":"665385","name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"citation":{"ista":"Boocock DR. 2023. Mechanochemical pattern formation across biological scales. Institute of Science and Technology Austria.","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.","short":"D.R. Boocock, Mechanochemical Pattern Formation across Biological Scales, Institute of Science and Technology Austria, 2023.","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","ama":"Boocock DR. Mechanochemical pattern formation across biological scales. 2023. doi:10.15479/at:ista:12964","mla":"Boocock, Daniel R. Mechanochemical Pattern Formation across Biological Scales. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:12964."},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","author":[{"last_name":"Boocock","orcid":"0000-0002-1585-2631","full_name":"Boocock, Daniel R","id":"453AF628-F248-11E8-B48F-1D18A9856A87","first_name":"Daniel R"}],"article_processing_charge":"No","title":"Mechanochemical pattern formation across biological scales","publisher":"Institute of Science and Technology Austria","has_accepted_license":"1","year":"2023","day":"17","page":"146","doi":"10.15479/at:ista:12964","date_published":"2023-05-17T00:00:00Z","date_created":"2023-05-15T14:52:36Z","_id":"12964","type":"dissertation","tmp":{"name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","image":"/images/cc_by_nc_sa.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","short":"CC BY-NC-SA (4.0)"},"status":"public","supervisor":[{"last_name":"Hannezo","full_name":"Hannezo, Edouard B","orcid":"0000-0001-6005-1561","first_name":"Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87"}],"date_updated":"2023-08-04T11:02:40Z","ddc":["530"],"file_date_updated":"2023-05-19T07:04:25Z","department":[{"_id":"GradSch"},{"_id":"EdHa"}],"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."}],"oa_version":"Published Version","alternative_title":["ISTA Thesis"],"month":"05","publication_identifier":{"issn":["2663-337X"],"isbn":["978-3-99078-032-9"]},"publication_status":"published","degree_awarded":"PhD","file":[{"content_type":"application/pdf","embargo_to":"open_access","access_level":"closed","relation":"main_file","checksum":"d51240675fc6dc0e3f5dc0c902695d3a","file_id":"12988","embargo":"2024-05-17","date_updated":"2023-05-19T07:04:25Z","file_size":40414730,"creator":"dboocock","date_created":"2023-05-17T13:39:54Z","file_name":"thesis_boocock.pdf"},{"content_type":"application/zip","relation":"source_file","access_level":"closed","checksum":"581a2313ffeb40fe77e8a122a25a7795","file_id":"12989","file_size":34338567,"date_updated":"2023-05-17T14:35:13Z","creator":"dboocock","file_name":"thesis_boocock.zip","date_created":"2023-05-17T13:39:53Z"}],"language":[{"iso":"eng"}],"related_material":{"record":[{"status":"public","id":"8602","relation":"part_of_dissertation"}]},"ec_funded":1},{"acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"NanoFab"}],"abstract":[{"lang":"eng","text":"High-performance semiconductors rely upon precise control of heat and charge transport. This can be achieved by precisely engineering defects in polycrystalline solids. There are multiple approaches to preparing such polycrystalline semiconductors, and the transformation of solution-processed colloidal nanoparticles is appealing because colloidal nanoparticles combine low cost with structural and compositional tunability along with rich surface chemistry. However, the multiple processes from nanoparticle synthesis to the final bulk nanocomposites are very complex. They involve nanoparticle purification, post-synthetic modifications, and finally consolidation (thermal treatments and densification). All these properties dictate the final material’s composition and microstructure, ultimately affecting its functional properties. This thesis explores the synthesis, surface chemistry and consolidation of colloidal semiconductor nanoparticles into dense solids. In particular, the transformations that take place during these processes, and their effect on the material’s transport properties are evaluated. "}],"oa_version":"Published Version","alternative_title":["ISTA Thesis"],"month":"04","publication_status":"published","degree_awarded":"PhD","publication_identifier":{"isbn":["978-3-99078-028-2"],"issn":["2663-337X"]},"language":[{"iso":"eng"}],"file":[{"date_created":"2023-05-02T07:43:18Z","file_name":"Thesis_Calcabrini.docx","date_updated":"2023-05-02T07:43:18Z","file_size":99627036,"creator":"mcalcabr","checksum":"9347b0e09425f56fdcede5d3528404dc","file_id":"12887","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","access_level":"closed","relation":"source_file"},{"file_id":"12888","checksum":"2d188b76621086cd384f0b9264b0a576","success":1,"access_level":"open_access","relation":"main_file","content_type":"application/pdf","date_created":"2023-05-02T07:42:45Z","file_name":"Thesis_Calcabrini_pdfa.pdf","creator":"mcalcabr","date_updated":"2023-05-02T07:42:45Z","file_size":8742220}],"ec_funded":1,"related_material":{"record":[{"id":"10806","status":"public","relation":"part_of_dissertation"},{"id":"10042","status":"public","relation":"part_of_dissertation"},{"status":"public","id":"12237","relation":"part_of_dissertation"},{"id":"9118","status":"public","relation":"part_of_dissertation"},{"status":"public","id":"10123","relation":"part_of_dissertation"}]},"_id":"12885","type":"dissertation","status":"public","date_updated":"2023-08-14T07:25:26Z","supervisor":[{"last_name":"Ibáñez","full_name":"Ibáñez, Maria","orcid":"0000-0001-5013-2843","id":"43C61214-F248-11E8-B48F-1D18A9856A87","first_name":"Maria"}],"ddc":["546","541"],"department":[{"_id":"GradSch"},{"_id":"MaIb"}],"file_date_updated":"2023-05-02T07:43:18Z","oa":1,"publisher":"Institute of Science and Technology Austria","year":"2023","has_accepted_license":"1","day":"28","page":"82","date_created":"2023-05-02T07:58:57Z","date_published":"2023-04-28T00:00:00Z","doi":"10.15479/at:ista:12885","project":[{"grant_number":"665385","name":"International IST Doctoral Program","call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"}],"citation":{"chicago":"Calcabrini, Mariano. “Nanoparticle-Based Semiconductor Solids: From Synthesis to Consolidation.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:12885.","ista":"Calcabrini M. 2023. Nanoparticle-based semiconductor solids: From synthesis to consolidation. Institute of Science and Technology Austria.","mla":"Calcabrini, Mariano. Nanoparticle-Based Semiconductor Solids: From Synthesis to Consolidation. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:12885.","apa":"Calcabrini, M. (2023). Nanoparticle-based semiconductor solids: From synthesis to consolidation. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12885","ama":"Calcabrini M. Nanoparticle-based semiconductor solids: From synthesis to consolidation. 2023. doi:10.15479/at:ista:12885","ieee":"M. Calcabrini, “Nanoparticle-based semiconductor solids: From synthesis to consolidation,” Institute of Science and Technology Austria, 2023.","short":"M. Calcabrini, Nanoparticle-Based Semiconductor Solids: From Synthesis to Consolidation, Institute of Science and Technology Austria, 2023."},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","article_processing_charge":"No","author":[{"first_name":"Mariano","id":"45D7531A-F248-11E8-B48F-1D18A9856A87","last_name":"Calcabrini","full_name":"Calcabrini, Mariano","orcid":"0000-0003-4566-5877"}],"title":"Nanoparticle-based semiconductor solids: From synthesis to consolidation"},{"related_material":{"record":[{"id":"11470","status":"public","relation":"part_of_dissertation"},{"status":"public","id":"8308","relation":"part_of_dissertation"},{"relation":"part_of_dissertation","status":"public","id":"11469"},{"relation":"part_of_dissertation","status":"public","id":"12750"}]},"ec_funded":1,"file":[{"date_created":"2023-03-23T16:42:56Z","file_name":"Thesis_sub_PBrighi.zip","creator":"pbrighi","date_updated":"2023-03-23T16:42:56Z","file_size":42167561,"checksum":"5d2de651ef9449c1b8dc27148ca74777","file_id":"12753","access_level":"closed","relation":"source_file","content_type":"application/zip"},{"date_updated":"2023-03-23T16:43:14Z","file_size":13977000,"creator":"pbrighi","date_created":"2023-03-23T16:43:14Z","file_name":"Thesis_PBrighi.pdf","content_type":"application/pdf","access_level":"open_access","relation":"main_file","file_id":"12754","checksum":"7caa153d4a5b0873a79358787d2dfe1e","success":1}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2663-337X"]},"publication_status":"published","degree_awarded":"PhD","month":"03","alternative_title":["ISTA Thesis"],"oa_version":"None","acknowledged_ssus":[{"_id":"ScienComp"}],"abstract":[{"lang":"eng","text":"Nonergodic systems, whose out-of-equilibrium dynamics fail to thermalize, provide a fascinating research direction both for fundamental reasons and for application in state of the art quantum devices.\r\nGoing beyond the description of statistical mechanics, ergodicity breaking yields a new paradigm in quantum many-body physics, introducing novel phases of matter with no counterpart at equilibrium.\r\nIn this Thesis, we address different open questions in the field, focusing on disorder-induced many-body localization (MBL) and on weak ergodicity breaking in kinetically constrained models.\r\nIn particular, we contribute to the debate about transport in kinetically constrained models, studying the effect of $U(1)$ conservation and inversion-symmetry breaking in a family of quantum East models.\r\nUsing tensor network techniques, we analyze the dynamics of large MBL systems beyond the limit of exact numerical methods.\r\nIn this setting, we approach the debated topic of the coexistence of localized and thermal eigenstates separated by energy thresholds known as many-body mobility edges.\r\nInspired by recent experiments, our work further investigates the localization of a small bath induced by the coupling to a large localized chain, the so-called MBL proximity effect.\r\n\r\nIn the first Chapter, we introduce a family of particle-conserving kinetically constrained models, inspired by the quantum East model.\r\nThe system we study features strong inversion-symmetry breaking, due to the nature of the correlated hopping.\r\nWe show that these models host so-called quantum Hilbert space fragmentation, consisting of disconnected subsectors in an entangled basis, and further provide an analytical description of this phenomenon.\r\nWe further probe its effect on dynamics of simple product states, showing revivals in fidelity and local observalbes.\r\nThe study of dynamics within the largest subsector reveals an anomalous transient superdiffusive behavior crossing over to slow logarithmic dynamics at later times.\r\nThis work suggests that particle conserving constrained models with inversion-symmetry breaking realize new universality classes of dynamics and invite their further theoretical and experimental studies.\r\n\r\nNext, we use kinetic constraints and disorder to design a model with many-body mobility edges in particle density.\r\nThis feature allows to study the dynamics of localized and thermal states in large systems beyond the limitations of previous studies.\r\nThe time-evolution shows typical signatures of localization at small densities, replaced by thermal behavior at larger densities.\r\nOur results provide evidence in favor of the stability of many-body mobility edges, which was recently challenged by a theoretical argument.\r\nTo support our findings, we probe the mechanism proposed as a cause of delocalization in many-body localized systems with mobility edges suggesting its ineffectiveness in the model studied.\r\n\r\nIn the last Chapter of this Thesis, we address the topic of many-body localization proximity effect.\r\nWe study a model inspired by recent experiments, featuring Anderson localized coupled to a small bath of free hard-core bosons.\r\nThe interaction among the two particle species results in non-trivial dynamics, which we probe using tensor network techniques.\r\nOur simulations show convincing evidence of many-body localization proximity effect when the bath is composed by a single free particle and interactions are strong.\r\nWe furthter observe an anomalous entanglement dynamics, which we explain through a phenomenological theory.\r\nFinally, we extract highly excited eigenstates of large systems, providing supplementary evidence in favor of our findings."}],"department":[{"_id":"GradSch"},{"_id":"MaSe"}],"file_date_updated":"2023-03-23T16:43:14Z","ddc":["530"],"supervisor":[{"first_name":"Maksym","id":"47809E7E-F248-11E8-B48F-1D18A9856A87","last_name":"Serbyn","full_name":"Serbyn, Maksym","orcid":"0000-0002-2399-5827"}],"date_updated":"2023-09-20T10:44:12Z","status":"public","type":"dissertation","tmp":{"name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","image":"/images/cc_by_nc_sa.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","short":"CC BY-NC-SA (4.0)"},"_id":"12732","date_published":"2023-03-21T00:00:00Z","doi":"10.15479/at:ista:12732","date_created":"2023-03-17T13:30:48Z","page":"158","day":"21","has_accepted_license":"1","year":"2023","publisher":"Institute of Science and Technology Austria","oa":1,"title":"Ergodicity breaking in disordered and kinetically constrained quantum many-body systems","author":[{"first_name":"Pietro","id":"4115AF5C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7969-2729","full_name":"Brighi, Pietro","last_name":"Brighi"}],"article_processing_charge":"No","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","citation":{"ama":"Brighi P. Ergodicity breaking in disordered and kinetically constrained quantum many-body systems. 2023. doi:10.15479/at:ista:12732","apa":"Brighi, P. (2023). Ergodicity breaking in disordered and kinetically constrained quantum many-body systems. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12732","short":"P. Brighi, Ergodicity Breaking in Disordered and Kinetically Constrained Quantum Many-Body Systems, Institute of Science and Technology Austria, 2023.","ieee":"P. Brighi, “Ergodicity breaking in disordered and kinetically constrained quantum many-body systems,” Institute of Science and Technology Austria, 2023.","mla":"Brighi, Pietro. Ergodicity Breaking in Disordered and Kinetically Constrained Quantum Many-Body Systems. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:12732.","ista":"Brighi P. 2023. Ergodicity breaking in disordered and kinetically constrained quantum many-body systems. Institute of Science and Technology Austria.","chicago":"Brighi, Pietro. “Ergodicity Breaking in Disordered and Kinetically Constrained Quantum Many-Body Systems.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:12732."},"project":[{"name":"Non-Ergodic Quantum Matter: Universality, Dynamics and Control","grant_number":"850899","call_identifier":"H2020","_id":"23841C26-32DE-11EA-91FC-C7463DDC885E"}]},{"has_accepted_license":"1","year":"2023","day":"23","page":"260","doi":"10.15479/at:ista:12726","date_published":"2023-03-23T00:00:00Z","date_created":"2023-03-15T13:22:13Z","publisher":"Institute of Science and Technology Austria","citation":{"chicago":"Riedl, Michael. “Synchronization in Collectively Moving Active Matter.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:12726.","ista":"Riedl M. 2023. Synchronization in collectively moving active matter. Institute of Science and Technology Austria.","mla":"Riedl, Michael. Synchronization in Collectively Moving Active Matter. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:12726.","apa":"Riedl, M. (2023). Synchronization in collectively moving active matter. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12726","ama":"Riedl M. Synchronization in collectively moving active matter. 2023. doi:10.15479/at:ista:12726","ieee":"M. Riedl, “Synchronization in collectively moving active matter,” Institute of Science and Technology Austria, 2023.","short":"M. Riedl, Synchronization in Collectively Moving Active Matter, Institute of Science and Technology Austria, 2023."},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","author":[{"orcid":"0000-0003-4844-6311","full_name":"Riedl, Michael","last_name":"Riedl","first_name":"Michael","id":"3BE60946-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"No","title":"Synchronization in collectively moving active matter","publication_identifier":{"issn":["2663-337X"]},"degree_awarded":"PhD","publication_status":"published","file":[{"creator":"cchlebak","file_size":63734746,"date_updated":"2023-11-24T11:57:46Z","file_name":"Thesis_Riedl_2023.pdf","date_created":"2023-03-23T12:49:23Z","relation":"main_file","access_level":"closed","description":"the main file is missing the bibliography. See new thesis record 14530 for updated files.","content_type":"application/pdf","checksum":"eba0e19fe57a8c15e7aeab55a845efb7","file_id":"12745"},{"date_created":"2023-03-23T12:54:34Z","file_name":"Thesis_Riedl_2023_source.rar","date_updated":"2023-09-24T22:30:03Z","file_size":339473651,"creator":"cchlebak","checksum":"0eb7b650cc8ae843bcec7c8a6109ae03","file_id":"12746","content_type":"application/octet-stream","embargo_to":"open_access","access_level":"closed","relation":"source_file"}],"language":[{"iso":"eng"}],"related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"10703"},{"status":"public","id":"10791","relation":"part_of_dissertation"},{"status":"public","id":"7932","relation":"part_of_dissertation"},{"relation":"part_of_dissertation","status":"public","id":"461"},{"id":"14530","status":"public","relation":"new_edition"}]},"acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"Bio"}],"abstract":[{"lang":"eng","text":"Most motions of many-body systems at any scale in nature with sufficient degrees\r\nof freedom tend to be chaotic; reaching from the orbital motion of planets, the air\r\ncurrents in our atmosphere, down to the water flowing through our pipelines or\r\nthe movement of a population of bacteria. To the observer it is therefore intriguing\r\nwhen a moving collective exhibits order. Collective motion of flocks of birds, schools\r\nof fish or swarms of self-propelled particles or robots have been studied extensively\r\nover the past decades but the mechanisms involved in the transition from chaos to\r\norder remain unclear. Here, the interactions, that in most systems give rise to chaos,\r\nsustain order. In this thesis we investigate mechanisms that preserve, destabilize\r\nor lead to the ordered state. We show that endothelial cells migrating in circular\r\nconfinements transition to a collective rotating state and concomitantly synchronize\r\nthe frequencies of nucleating actin waves within individual cells. Consequently,\r\nthe frequency dependent cell migration speed uniformizes across the population.\r\nComplementary to the WAVE dependent nucleation of traveling actin waves, we\r\nshow that in leukocytes the actin polymerization depending on WASp generates\r\npushing forces locally at stationary patches. Next, in pipe flows, we study methods\r\nto disrupt the self–sustaining cycle of turbulence and therefore relaminarize the\r\nflow. While we find in pulsating flow conditions that turbulence emerges through a\r\nhelical instability during the decelerating phase. Finally, we show quantitatively in\r\nbrain slices of mice that wild-type control neurons can compensate the migratory\r\ndeficits of a genetically modified neuronal sub–population in the developing cortex."}],"oa_version":"None","alternative_title":["ISTA Thesis"],"month":"03","supervisor":[{"last_name":"Hof","orcid":"0000-0003-2057-2754","full_name":"Hof, Björn","id":"3A374330-F248-11E8-B48F-1D18A9856A87","first_name":"Björn"}],"date_updated":"2023-11-30T10:55:13Z","ddc":["530"],"department":[{"_id":"GradSch"},{"_id":"BjHo"}],"file_date_updated":"2023-11-24T11:57:46Z","_id":"12726","type":"dissertation","status":"public"},{"ec_funded":1,"related_material":{"record":[{"relation":"research_data","status":"public","id":"9803"},{"relation":"research_data","status":"public","id":"12933"},{"relation":"part_of_dissertation","status":"public","id":"6831"},{"id":"14077","status":"public","relation":"part_of_dissertation"}]},"degree_awarded":"PhD","publication_status":"published","publication_identifier":{"isbn":["978-3-99078-035-0"],"issn":["2663-337X"]},"language":[{"iso":"eng"}],"file":[{"file_name":"Thesis_latex_forpdfa.zip","date_created":"2023-08-16T18:15:17Z","creator":"gpuixeus","file_size":10891454,"date_updated":"2023-08-17T06:55:24Z","checksum":"4e44e169f2724ee8c9324cd60bcc2b71","file_id":"14075","relation":"source_file","access_level":"closed","content_type":"application/zip"},{"file_name":"PhDThesis_PuixeuG.pdf","date_created":"2023-08-18T10:47:55Z","file_size":19856686,"date_updated":"2023-08-18T10:47:55Z","creator":"gpuixeus","success":1,"checksum":"e10b04cd8f3fecc0d9ef6e6868b6e1e8","file_id":"14079","content_type":"application/pdf","relation":"main_file","access_level":"open_access"}],"alternative_title":["ISTA Thesis"],"month":"08","abstract":[{"lang":"eng","text":"Females and males across species are subject to divergent selective pressures arising\r\nfrom di↵erent reproductive interests and ecological niches. This often translates into a\r\nintricate array of sex-specific natural and sexual selection on traits that have a shared\r\ngenetic basis between both sexes, causing a genetic sexual conflict. The resolution of\r\nthis conflict mostly relies on the evolution of sex-specific expression of the shared genes,\r\nleading to phenotypic sexual dimorphism. Such sex-specific gene expression is thought\r\nto evolve via modifications of the genetic networks ultimately linked to sex-determining\r\ntranscription factors. Although much empirical and theoretical evidence supports this\r\nstandard picture of the molecular basis of sexual conflict resolution, there still are a\r\nfew open questions regarding the complex array of selective forces driving phenotypic\r\ndi↵erentiation between the sexes, as well as the molecular mechanisms underlying sexspecific adaptation. I address some of these open questions in my PhD thesis.\r\nFirst, how do patterns of phenotypic sexual dimorphism vary within populations,\r\nas a response to the temporal and spatial changes in sex-specific selective forces? To\r\ntackle this question, I analyze the patterns of sex-specific phenotypic variation along\r\nthree life stages and across populations spanning the whole geographical range of Rumex\r\nhastatulus, a wind-pollinated angiosperm, in the first Chapter of the thesis.\r\nSecond, how do gene expression patterns lead to phenotypic dimorphism, and what\r\nare the molecular mechanisms underlying the observed transcriptomic variation? I\r\naddress this question by examining the sex- and tissue-specific expression variation in\r\nnewly-generated datasets of sex-specific expression in heads and gonads of Drosophila\r\nmelanogaster. I additionally used two complementary approaches for the study of the\r\ngenetic basis of sex di↵erences in gene expression in the second and third Chapters of\r\nthe thesis.\r\nThird, how does intersex correlation, thought to be one of the main aspects constraining the ability for the two sexes to decouple, interact with the evolution of sexual\r\ndimorphism? I develop models of sex-specific stabilizing selection, mutation and drift\r\nto formalize common intuition regarding the patterns of covariation between intersex\r\ncorrelation and sexual dimorphism in the fourth Chapter of the thesis.\r\nAlltogether, the work described in this PhD thesis provides useful insights into the\r\nlinks between genetic, transcriptomic and phenotypic layers of sex-specific variation,\r\nand contributes to our general understanding of the dynamics of sexual dimorphism\r\nevolution."}],"oa_version":"Published Version","file_date_updated":"2023-08-18T10:47:55Z","department":[{"_id":"GradSch"},{"_id":"NiBa"},{"_id":"BeVi"}],"date_updated":"2023-12-13T12:15:36Z","supervisor":[{"last_name":"Vicoso","full_name":"Vicoso, Beatriz","orcid":"0000-0002-4579-8306","id":"49E1C5C6-F248-11E8-B48F-1D18A9856A87","first_name":"Beatriz"},{"id":"4880FE40-F248-11E8-B48F-1D18A9856A87","first_name":"Nicholas H","last_name":"Barton","full_name":"Barton, Nicholas H","orcid":"0000-0002-8548-5240"}],"ddc":["576"],"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","status":"public","_id":"14058","page":"230","date_created":"2023-08-15T10:20:40Z","doi":"10.15479/at:ista:14058","date_published":"2023-08-15T00:00:00Z","year":"2023","has_accepted_license":"1","day":"15","oa":1,"publisher":"Institute of Science and Technology Austria","article_processing_charge":"No","author":[{"last_name":"Puixeu Sala","full_name":"Puixeu Sala, Gemma","orcid":"0000-0001-8330-1754","first_name":"Gemma","id":"33AB266C-F248-11E8-B48F-1D18A9856A87"}],"title":"The molecular basis of sexual dimorphism: Experimental and theoretical characterization of phenotypic, transcriptomic and genetic patterns of sex-specific adaptation","citation":{"mla":"Puixeu Sala, Gemma. The Molecular Basis of Sexual Dimorphism: Experimental and Theoretical Characterization of Phenotypic, Transcriptomic and Genetic Patterns of Sex-Specific Adaptation. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:14058.","short":"G. Puixeu Sala, The Molecular Basis of Sexual Dimorphism: Experimental and Theoretical Characterization of Phenotypic, Transcriptomic and Genetic Patterns of Sex-Specific Adaptation, Institute of Science and Technology Austria, 2023.","ieee":"G. Puixeu Sala, “The molecular basis of sexual dimorphism: Experimental and theoretical characterization of phenotypic, transcriptomic and genetic patterns of sex-specific adaptation,” Institute of Science and Technology Austria, 2023.","ama":"Puixeu Sala G. The molecular basis of sexual dimorphism: Experimental and theoretical characterization of phenotypic, transcriptomic and genetic patterns of sex-specific adaptation. 2023. doi:10.15479/at:ista:14058","apa":"Puixeu Sala, G. (2023). The molecular basis of sexual dimorphism: Experimental and theoretical characterization of phenotypic, transcriptomic and genetic patterns of sex-specific adaptation. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:14058","chicago":"Puixeu Sala, Gemma. “The Molecular Basis of Sexual Dimorphism: Experimental and Theoretical Characterization of Phenotypic, Transcriptomic and Genetic Patterns of Sex-Specific Adaptation.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:14058.","ista":"Puixeu Sala G. 2023. The molecular basis of sexual dimorphism: Experimental and theoretical characterization of phenotypic, transcriptomic and genetic patterns of sex-specific adaptation. Institute of Science and Technology Austria."},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","project":[{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"International IST Doctoral Program","grant_number":"665385"},{"grant_number":"25817","name":"Sexual conflict: resolution, constraints and biomedical implications","_id":"9B9DFC9E-BA93-11EA-9121-9846C619BF3A"}]},{"project":[{"_id":"2595697A-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Self-Organization of the Bacterial Cell","grant_number":"679239"},{"_id":"fc38323b-9c52-11eb-aca3-ff8afb4a011d","name":"Understanding bacterial cell division by in vitro\r\nreconstitution","grant_number":"P34607"},{"_id":"2596EAB6-B435-11E9-9278-68D0E5697425","name":"Synthesis of bacterial cell wall","grant_number":"ALTF 2015-1163"},{"name":"Reconstitution of bacterial cell wall sythesis","grant_number":"LT000824/2016","_id":"259B655A-B435-11E9-9278-68D0E5697425"}],"citation":{"ista":"Radler P. 2023. Spatiotemporal signaling during assembly of the bacterial divisome. Institute of Science and Technology Austria.","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.","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","ieee":"P. Radler, “Spatiotemporal signaling during assembly of the bacterial divisome,” Institute of Science and Technology Austria, 2023.","short":"P. Radler, Spatiotemporal Signaling during Assembly of the Bacterial Divisome, Institute of Science and Technology Austria, 2023.","mla":"Radler, Philipp. Spatiotemporal Signaling during Assembly of the Bacterial Divisome. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:14280."},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","article_processing_charge":"No","author":[{"first_name":"Philipp","id":"40136C2A-F248-11E8-B48F-1D18A9856A87","full_name":"Radler, Philipp","orcid":"0000-0001-9198-2182 ","last_name":"Radler"}],"title":"Spatiotemporal signaling during assembly of the bacterial divisome","publisher":"Institute of Science and Technology Austria","year":"2023","has_accepted_license":"1","day":"25","page":"156","date_created":"2023-09-06T10:58:25Z","date_published":"2023-09-25T00:00:00Z","doi":"10.15479/at:ista:14280","_id":"14280","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","keyword":["Cell Division","Reconstitution","FtsZ","FtsA","Divisome","E.coli"],"status":"public","date_updated":"2024-02-21T12:35:18Z","supervisor":[{"first_name":"Martin","id":"462D4284-F248-11E8-B48F-1D18A9856A87","last_name":"Loose","orcid":"0000-0001-7309-9724","full_name":"Loose, Martin"}],"ddc":["572"],"file_date_updated":"2023-10-04T10:28:35Z","department":[{"_id":"GradSch"},{"_id":"MaLo"}],"abstract":[{"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.","lang":"eng"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"oa_version":"Published Version","alternative_title":["ISTA Thesis"],"month":"09","degree_awarded":"PhD","publication_status":"published","publication_identifier":{"issn":["2663-337X"],"isbn":["978-3-99078-033-6"]},"language":[{"iso":"eng"}],"file":[{"file_size":114932847,"date_updated":"2023-10-04T10:28:35Z","creator":"pradler","file_name":"PhD Thesis_Philipp Radler_20231004.docx","date_created":"2023-10-04T10:11:53Z","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","relation":"source_file","access_level":"closed","checksum":"87eef11fbc5c7df0826f12a3a629b444","file_id":"14390"},{"file_size":37838778,"date_updated":"2023-10-04T10:28:35Z","creator":"pradler","file_name":"PhD Thesis_Philipp Radler_20231004.pdf","date_created":"2023-10-04T10:11:21Z","embargo_to":"open_access","content_type":"application/pdf","relation":"main_file","access_level":"closed","embargo":"2024-10-04","checksum":"3253e099b7126469d941fd9419d68b4f","file_id":"14391"}],"ec_funded":1,"related_material":{"record":[{"relation":"part_of_dissertation","id":"11373","status":"public"},{"relation":"part_of_dissertation","status":"public","id":"7387"},{"relation":"research_data","status":"public","id":"10934"}]}},{"project":[{"name":"Integrated visual proteomics of reciprocal cell-extracellular matrix interactions","_id":"eba3b5f6-77a9-11ec-83b8-cf0905748aa3"},{"_id":"059B463C-7A3F-11EA-A408-12923DDC885E","name":"NÖ-Fonds Preis für die Jungforscherin des Jahres am IST Austria"}],"article_processing_charge":"No","author":[{"last_name":"Zens","orcid":"0000-0002-9561-1239","full_name":"Zens, Bettina","id":"45FD126C-F248-11E8-B48F-1D18A9856A87","first_name":"Bettina"}],"title":"Ultrastructural characterization of natively preserved extracellular matrix by cryo-electron tomography","citation":{"short":"B. Zens, Ultrastructural Characterization of Natively Preserved Extracellular Matrix by Cryo-Electron Tomography, Institute of Science and Technology Austria, 2023.","ieee":"B. Zens, “Ultrastructural characterization of natively preserved extracellular matrix by cryo-electron tomography,” Institute of Science and Technology Austria, 2023.","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","ama":"Zens B. Ultrastructural characterization of natively preserved extracellular matrix by cryo-electron tomography. 2023. doi:10.15479/at:ista:12491","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.","ista":"Zens B. 2023. Ultrastructural characterization of natively preserved extracellular matrix by cryo-electron tomography. Institute of Science and Technology Austria.","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."},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","oa":1,"publisher":"Institute of Science and Technology Austria","page":"187","date_created":"2023-02-02T14:50:20Z","date_published":"2023-02-02T00:00:00Z","doi":"10.15479/at:ista:12491","year":"2023","has_accepted_license":"1","day":"02","type":"dissertation","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"],"status":"public","_id":"12491","file_date_updated":"2024-02-08T23:30:04Z","department":[{"_id":"GradSch"},{"_id":"FlSc"}],"date_updated":"2024-03-25T23:30:05Z","supervisor":[{"full_name":"Schur, Florian KM","orcid":"0000-0003-4790-8078","last_name":"Schur","first_name":"Florian KM","id":"48AD8942-F248-11E8-B48F-1D18A9856A87"}],"ddc":["570"],"alternative_title":["ISTA Thesis"],"month":"02","abstract":[{"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.","lang":"eng"}],"acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"},{"_id":"Bio"}],"oa_version":"Published Version","related_material":{"record":[{"relation":"part_of_dissertation","id":"8586","status":"public"}]},"degree_awarded":"PhD","publication_status":"published","publication_identifier":{"issn":["2663-337X"],"isbn":["978-3-99078-027-5"]},"language":[{"iso":"eng"}],"file":[{"creator":"bzens","file_size":23082464,"date_updated":"2024-02-08T23:30:04Z","file_name":"PhDThesis_BettinaZens_2023_final.pdf","date_created":"2023-02-07T13:07:38Z","relation":"main_file","access_level":"open_access","content_type":"application/pdf","embargo":"2024-02-07","file_id":"12527","checksum":"069d87f025e0799bf9e3c375664264f2"},{"file_name":"PhDThesis_BettinaZens_2023_final.docx","date_created":"2023-02-07T13:09:05Z","file_size":106169509,"date_updated":"2024-02-08T23:30:04Z","creator":"bzens","file_id":"12528","checksum":"8c66ed203495d6e078ed1002a866520c","embargo_to":"open_access","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","relation":"source_file","access_level":"closed"}]}]