--- OA_place: publisher _id: '17119' abstract: - lang: eng text: "Genomes are shaped by natural selection at the level of the organism, as genomic variants that\r\nhave a beneficial effect on the viability or fecundity of their carriers are on average expected\r\nto be passed on to more offspring than less beneficial alleles. However, selection also favors\r\ngenomic variants that drive their own transmission to the next generation above the mendelian\r\nexpectation of 50 percent in heterozygotes, even if these self-promoting variants are less\r\nbeneficial to the organism than other variants at the same locus. Such variants, called meiotic\r\ndrivers, are found in diverse taxa, and often impose fitness costs on their host organisms. As\r\nmeiotic drivers often require multiple genes and sequences for transmission ratio distortion,\r\nthey are often found in regions of low recombination, such as inversions, which prevent their\r\nrecombination with the non-driving homologous regions. Reduced recombination rates are\r\nexpected to lead to the accumulation of deleterious mutations, which may affect hundreds\r\nof genes trapped in the inversions of meiotic drivers. Although the observed fitness costs of\r\nself-promoting haplotypes are thought to possibly reflect sequence degeneration, no study has\r\nsystematically investigated the level of degeneration on a meiotic driver. Further, the low\r\nrates of recombination between driving and non-driving haplotypes have limited the power of\r\ntraditional genetic studies in uncovering the gene content of meiotic drivers, and made the\r\nthe identification of the genes causing transmission ratio distortion difficult.\r\nAfter an introduction to meiotic drivers in Chapter 1, this thesis presents three studies that\r\nmake use of next generation sequencing data to characterize the sequence and expression\r\nevolution of genes on the t-haplotype, a large and ancient meiotic driver in house mice that is\r\ntransmitted to up to 100% of the offspring in males heterozygous for it. Chapter 2 presents\r\na comprehensive assessment of the t-haplotype’s sequence evolution, which shows signs of\r\nsequence degeneration counteracted by occasional recombination with the non-driving homolog\r\nover large parts of the meiotic driver, proposing an explanation for its long-term survival.\r\nChapter 3 investigates the sequence and expression evolution of genes on the t-haplotype,\r\nand finds widespread expression and copy number changes and signs of less efficient purifying\r\nselection compared to the genes on the non-driving homolog. Further, this chapter finds\r\ncandidates for involvment in drive: two positively selected genes on the t-haplotype, and\r\nthe discovery of a t-specific gene duplicate, which was gained from another chromosome,\r\nand which acquired novel sequence and testis-specific expression on the t-haplotype. Finally,\r\nChapter 4 provides unprecedented insights into the gene expression landscape in testes of\r\nt-carrier mice, using single nucleus sequencing. Cell-resolved RNA-sequencing allows the\r\ncomparison of expression in spermatids carrying or not carrying the t-haplotype as well as the\r\ntiming of t-haplotype-induced expression changes along spermatogenesis. This study shows\r\nthe timing of previously found drive-associated genes, and uncovers novel candidate genes and\r\nbiological processes that may underlie the complex biology of transmission ratio distortion of\r\nthe t-haplotype. Chapter 5 synthesizes the findings of the three studies, and discusses them in\r\nthe context of the current state of meiotic drive research." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Réka K full_name: Kelemen, Réka K id: 48D3F8DE-F248-11E8-B48F-1D18A9856A87 last_name: Kelemen orcid: 0000-0002-8489-9281 citation: ama: Kelemen RK. Characterizing the sequence and expression evolution of the t-haplotype, a model meiotic driver. 2024. doi:10.15479/at:ista:17119 apa: Kelemen, R. K. (2024). Characterizing the sequence and expression evolution of the t-haplotype, a model meiotic driver. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:17119 chicago: Kelemen, Réka K. “Characterizing the Sequence and Expression Evolution of the T-Haplotype, a Model Meiotic Driver.” Institute of Science and Technology Austria, 2024. https://doi.org/10.15479/at:ista:17119. ieee: R. K. Kelemen, “Characterizing the sequence and expression evolution of the t-haplotype, a model meiotic driver,” Institute of Science and Technology Austria, 2024. ista: Kelemen RK. 2024. Characterizing the sequence and expression evolution of the t-haplotype, a model meiotic driver. Institute of Science and Technology Austria. mla: Kelemen, Réka K. Characterizing the Sequence and Expression Evolution of the T-Haplotype, a Model Meiotic Driver. Institute of Science and Technology Austria, 2024, doi:10.15479/at:ista:17119. short: R.K. Kelemen, Characterizing the Sequence and Expression Evolution of the T-Haplotype, a Model Meiotic Driver, Institute of Science and Technology Austria, 2024. corr_author: '1' date_created: 2024-06-07T16:14:13Z date_published: 2024-06-20T00:00:00Z date_updated: 2026-04-07T13:21:37Z day: '20' ddc: - '576' degree_awarded: PhD department: - _id: GradSch - _id: BeVi doi: 10.15479/at:ista:17119 ec_funded: 1 file: - access_level: closed checksum: fab59146e3b3dc2e5d214576984a2a63 content_type: application/zip creator: rkelemen date_created: 2024-06-07T16:09:17Z date_updated: 2025-01-10T23:30:10Z embargo_to: open_access file_id: '17121' file_name: thesis.zip file_size: 180557931 relation: source_file - access_level: open_access checksum: 91cc4c25a792239e8a7688e8aec7c62a content_type: application/pdf creator: rkelemen date_created: 2024-07-10T08:00:20Z date_updated: 2025-01-10T23:30:10Z embargo: 2025-01-10 file_id: '17213' file_name: thesis_to_archive.pdf file_size: 19405484 relation: main_file file_date_updated: 2025-01-10T23:30:10Z has_accepted_license: '1' keyword: - meiotic driver - neofunctionalization - single nucleus sequencing language: - iso: eng month: '06' oa: 1 oa_version: Published Version page: '105' project: - _id: 250BDE62-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '715257' name: Prevalence and Influence of Sexual Antagonism on Genome Evolution - _id: 34ae1506-11ca-11ed-8bc3-c14f4c474396 grant_number: F8810 name: The highjacking of meiosis for asexual reproduction publication_identifier: isbn: - 978-3-99078-039-8 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '542' relation: part_of_dissertation status: public - id: '10767' relation: part_of_dissertation status: public status: public supervisor: - first_name: Beatriz full_name: Vicoso, Beatriz id: 49E1C5C6-F248-11E8-B48F-1D18A9856A87 last_name: Vicoso orcid: 0000-0002-4579-8306 title: Characterizing the sequence and expression evolution of the t-haplotype, a model meiotic driver tmp: image: /images/cc_by_nc_sa.png legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) short: CC BY-NC-SA (4.0) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2024' ... --- OA_place: publisher _id: '18477' abstract: - lang: eng text: "ADAR1 is broadly expressed across various tissues and is vital in regulating pathways\r\nassociated with innate immune responses. ADAR1 marks double-stranded RNA as \"self\"\r\nthrough its A-to-I editing activity, effectively repressing autoimmunity and maintaining\r\nimmune tolerance. This editing process has been detected at millions of sites across the\r\nhuman genome. However, the mechanism underlying ADAR1's substrate selectivity\r\nproperties remains largely unclear, with much of the current knowledge derived from\r\ncomparisons to its more extensively studied homolog, ADAR2. By studying ADAR1 in complex\r\nwith its RNA substrates and applying a combination of biochemical techniques and structural\r\nstudies using CryoEM, we aim to gain a more comprehensive understanding of the substrate\r\nselectivity characteristics of ADAR1.\r\nIn this thesis, the purification protocol for ADAR1 was successfully optimized, resulting in the\r\nfirst report in the literature to achieve high protein purity and activity. This advancement\r\nenabled the investigation of complex formation between ADAR1 and various RNA substrates,\r\nleading to the identification of optimal conditions for preparing the cryoEM sample. However,\r\ndespite comprehensive optimization of the cryo-EM conditions, the resulting data lacked the\r\ndesired quality, highlighting the need for similar rigorous optimization of the RNA substrates\r\nto facilitate structural studies of the ADAR1-RNA complex. The study was complemented by\r\nAlphaFold predictions, which provided some insights into this mechanism.\r\nMoreover, during this project I established a collaboration with a research group focused on\r\nstudying ADAR homologs. Notably ADAR homologs were identified in bivalve species, and it\r\nwas further demonstrated that ADAR and its A-to-I editing activity are upregulated in Pacific\r\noysters during infections with Ostreid herpesvirus-1—a highly infectious virus that leads to\r\nsignificant losses in oyster populations globally. I successfully purified oyster ADAR and\r\nprepared in vitro edited RNA for nanopore sequencing—a direct sequencing technology\r\ncapable of detecting modified nucleotides without the need for reverse transcription. The\r\ncollaborators initiated optimization of this nanopore-based approach. However, current\r\ntechnological limitations still constrain the reliable detection of modified nucleotides.\r\nThe project also examined the impact of RNA editing on RNA binding and filament formation\r\nby MDA5, a key cytosolic dsRNA sensor that triggers an interferon response. A primary target\r\nof ADAR1's editing activity is RNA derived from repetitive elements present in the genome,\r\nparticularly Alu elements forming double-stranded RNA. When unedited, these RNA\r\nsequences are recognized by MDA5. However, the mechanisms by which MDA5 interacts with\r\nAlu RNAs, as well as the role of A-to-I editing in influencing this binding, are still not well\r\nunderstood.\r\nThe interaction between MDA5 and Alu elements, was successfully established. This was\r\nachieved through the testing of different RNA variants and the evaluation of filament\r\nformation using binding techniques and electron microscopy imaging. This groundwork has\r\nset the conditions for further evaluation using CryoEM. Furthermore, the effects of A-to-I\r\nediting on the binding properties of MDA5 with Alu RNA were investigated. Given the recent\r\nresearch that has provided new insights into MDA5's interaction with dsRNA, it is essential to\r\nrevise the experimental setup to integrate these findings before moving forward with the\r\nCryoEM sample analysis." acknowledged_ssus: - _id: EM-Fac - _id: LifeSc alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Beata M full_name: Kaczmarek, Beata M id: 36FA4AFA-F248-11E8-B48F-1D18A9856A87 last_name: Kaczmarek citation: ama: Kaczmarek BM. Biochemical and structural insights into ADAR1 RNA editing. 2024. doi:10.15479/at:ista:18477 apa: Kaczmarek, B. M. (2024). Biochemical and structural insights into ADAR1 RNA editing. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:18477 chicago: Kaczmarek, Beata M. “Biochemical and Structural Insights into ADAR1 RNA Editing.” Institute of Science and Technology Austria, 2024. https://doi.org/10.15479/at:ista:18477. ieee: B. M. Kaczmarek, “Biochemical and structural insights into ADAR1 RNA editing,” Institute of Science and Technology Austria, 2024. ista: Kaczmarek BM. 2024. Biochemical and structural insights into ADAR1 RNA editing. Institute of Science and Technology Austria. mla: Kaczmarek, Beata M. Biochemical and Structural Insights into ADAR1 RNA Editing. Institute of Science and Technology Austria, 2024, doi:10.15479/at:ista:18477. short: B.M. Kaczmarek, Biochemical and Structural Insights into ADAR1 RNA Editing, Institute of Science and Technology Austria, 2024. corr_author: '1' date_created: 2024-10-27T07:35:13Z date_published: 2024-10-29T00:00:00Z date_updated: 2026-04-07T13:23:59Z day: '29' ddc: - '572' degree_awarded: PhD department: - _id: GradSch - _id: CaBe doi: 10.15479/at:ista:18477 file: - access_level: closed checksum: 2053294ea4d770c495e4cc501e2a218b content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: bkaczmar date_created: 2024-10-29T11:56:36Z date_updated: 2025-10-29T23:30:02Z embargo_to: open_access file_id: '18485' file_name: 20241029_PhD_thesis_BKaczmarek.docx file_size: 23136626 relation: source_file - access_level: open_access checksum: 8ce857a4cd44b776791eaf180ac9dbb3 content_type: application/pdf creator: bkaczmar date_created: 2024-10-29T11:56:44Z date_updated: 2025-10-29T23:30:02Z embargo: 2025-10-29 file_id: '18486' file_name: 20241029_PhD_thesis_BKaczmarek.pdf file_size: 11707360 relation: main_file file_date_updated: 2025-10-29T23:30:02Z has_accepted_license: '1' language: - iso: eng month: '10' oa: 1 oa_version: Published Version page: '124' publication_identifier: isbn: - 978-3-99078-045-9 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria status: public supervisor: - first_name: Carrie A full_name: Bernecky, Carrie A id: 2CB9DFE2-F248-11E8-B48F-1D18A9856A87 last_name: Bernecky orcid: 0000-0003-0893-7036 title: Biochemical and structural insights into ADAR1 RNA editing tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2024' ... --- OA_place: publisher _id: '15352' abstract: - lang: eng text: "Epilepsy affects about 50 to 65 million people globally. It summarizes a spectrum of neurological\r\ndisorders that have in common a hyperactivity of the neuronal network resulting in seizures. A common\r\nassumption is that an imbalance between neuronal excitation and inhibition is a key mechanism in\r\nseizure generation and epileptogeneisis. In at least one-third of the patients, current therapies have\r\nproven unsuccessful in treating seizure progression. One potential reason could be that the therapies\r\nonly focus on neurons. Recent studies suggest that neuronal hyperactivity causes a microglial\r\nresponse, which reinstates brain homeostasis. Additionally, interactions between microglia and neurons\r\nhave been shown to inhibit neuronal firing and dampen seizure activity. However, the exact relationship\r\nbetween microglia and seizure progression in epilepsy is yet to be elucidated. A main bottleneck is that\r\nseveral studies investigate microglia dynamics in ex vivo slice models, which can severely affect the\r\nmicroglia dynamics due to their rapid response to environmental changes. On the other hand, in vivo\r\nstudies focus mostly on behavior characterization of the epileptic seizure phenotype and their long-term\r\nconsequences on microglia activity leaving out the direct consequences of acute seizure activity on\r\nmicroglia dynamics.\r\nHere, we perform a pilot study to combine electroencephalography (EEG) and in vivo live imaging to\r\ndirectly monitor and correlate the onset of seizure activity with microglia response. To induce seizures,\r\nwe take advantage of the kainic acid (KA) model, which represents similar neuropathological and\r\nelectroencephalographic features seen in human patients with temporal lobe epilepsy (TLE). After\r\nconfirmation of induction of the seizure and microglia activity in the hippocampus as a focal point, we\r\ninvestigated whether these changes also reached the primary visual cortex (V1) as a secondary\r\ngeneralized seizure activity. Indeed, we found that microglia changed their morphology at high doses\r\nof KA in the V1. Next, we optimized each of the two methodological components: for the EEG recording,\r\nour initial attempts under the microscope suffered from extensive electrical noise, which overlaid the\r\nactual signal. Thus, we built a customized Faraday-cage and confirmed that the signal-to-noise ratio\r\nwas sufficiently reduced to be able to record brain oscillatory activity. For the in vivo live imaging of\r\nmicroglia, we had to optimize the imaging parameters, so that we would be able to detect microglial\r\nprocesses in a sufficient resolution to track their process changes. Finally, we combined both\r\nmethodologies with the KA model. We confirmed that KA induced seizure activity and found first\r\nindication that those correlate with microglia volume changes.\r\nOverall, we have developed a first methodological approach, which allows the analysis of the acute\r\neffects of seizure onset on microglia. Future studies will have to continue to optimize the drift during\r\nimaging recording and the post-image analysis. " acknowledged_ssus: - _id: Bio - _id: LifeSc - _id: PreCl alternative_title: - ISTA Master's Thesis article_processing_charge: No author: - first_name: Julie Stefanie full_name: Murmann, Julie Stefanie id: 1d390868-f128-11eb-9611-a0ca5f7833b5 last_name: Murmann citation: ama: 'Murmann JS. Investigating acute microglia response to seizure activity in vivo: Combining 2-Photon imaging and EEG recording. 2024. doi:10.15479/at:ista:15352' apa: 'Murmann, J. S. (2024). Investigating acute microglia response to seizure activity in vivo: Combining 2-Photon imaging and EEG recording. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:15352' chicago: 'Murmann, Julie Stefanie. “Investigating Acute Microglia Response to Seizure Activity in Vivo: Combining 2-Photon Imaging and EEG Recording.” Institute of Science and Technology Austria, 2024. https://doi.org/10.15479/at:ista:15352.' ieee: 'J. S. Murmann, “Investigating acute microglia response to seizure activity in vivo: Combining 2-Photon imaging and EEG recording,” Institute of Science and Technology Austria, 2024.' ista: 'Murmann JS. 2024. Investigating acute microglia response to seizure activity in vivo: Combining 2-Photon imaging and EEG recording. Institute of Science and Technology Austria.' mla: 'Murmann, Julie Stefanie. Investigating Acute Microglia Response to Seizure Activity in Vivo: Combining 2-Photon Imaging and EEG Recording. Institute of Science and Technology Austria, 2024, doi:10.15479/at:ista:15352.' short: 'J.S. Murmann, Investigating Acute Microglia Response to Seizure Activity in Vivo: Combining 2-Photon Imaging and EEG Recording, Institute of Science and Technology Austria, 2024.' corr_author: '1' date_created: 2024-05-02T08:31:38Z date_published: 2024-05-02T00:00:00Z date_updated: 2026-04-07T13:05:00Z day: '02' ddc: - '570' degree_awarded: MS department: - _id: SaSi - _id: GradSch doi: 10.15479/at:ista:15352 file: - access_level: open_access checksum: 095817a6c944954ac3f277e547031a33 content_type: application/pdf creator: cchlebak date_created: 2024-05-02T12:26:13Z date_updated: 2025-05-02T22:30:04Z embargo: 2025-05-02 file_id: '15354' file_name: Murmann_Thesis_final_2024_2.pdf file_size: 5936142 relation: main_file - access_level: closed checksum: 43b632255372973a437ac87739cfd4db content_type: application/x-zip-compressed creator: cchlebak date_created: 2024-05-02T12:37:56Z date_updated: 2025-05-02T22:30:04Z embargo_to: open_access file_id: '15355' file_name: Murmann_Thesis_final_2024.zip file_size: 20645510 relation: source_file file_date_updated: 2025-05-02T22:30:04Z has_accepted_license: '1' language: - iso: eng month: '05' oa: 1 oa_version: Published Version page: '54' publication_identifier: issn: - 2791-4585 publication_status: published publisher: Institute of Science and Technology Austria status: public supervisor: - first_name: Sandra full_name: Siegert, Sandra id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 title: 'Investigating acute microglia response to seizure activity in vivo: Combining 2-Photon imaging and EEG recording' tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2024' ... --- OA_place: publisher _id: '14821' abstract: - lang: eng text: "The hippocampus is central to memory formation, storage and retrieval over many\r\ntimescales. Neurons in this brain area are highly selective to spatial position as well as to many\r\nother variables of the environment. It is believed that the selectivity patterns of hippocampal\r\nneurons reflect the structure of tasks an animal performs. However, especially at timescales\r\nlonger than a few minutes or hours it is not fully known how these representations evolve, nor\r\nhow they map to behaviour in the process. In this thesis, I monitored the evolution of\r\nhippocampal representations in a novel spatial-associative memory task for rats. Reward\r\nlocations were associated with global sensory cues (i.e. context); animals had to remember the\r\nassociations and dig for food in those locations only. I used in vivo electrophysiology to record\r\nthe activity of the hippocampus dorsal CA1 neurons during the learning period of a few days.\r\nI report here a novel and simple method to classify behaviour performance to account\r\nfor individual variability in learning speed and spurious performance unrelated to true task rule\r\nlearning. Using this classification I was then able to investigate neural responses on different\r\nstages of learning matched across animals. On the first day of learning, I observed a fast\r\nformation of single-cell selectivity to task variables which remained stable over days. I also\r\nobserved that reward tuning was not a single process but dependent on task-related cognitive\r\nload. At the population level, a linear decoding approach revealed a hierarchy in the\r\nrepresentation of task variables that changed with learning. In the high-dimensional space of\r\npopulation activity, the representation of contexts was specific to each position in the maze, and\r\ncould thus be better decoded if the position was known. The decoding of position did not improve\r\nwith knowledge of other variables. As learning progressed, the hippocampal code underwent a\r\nreorganisation of high-variance directions in population activity, identified by principal\r\ncomponent analysis. I found that dominant dimensions started carrying increasing amounts of\r\ninformation about task context specifically at those positions where it mattered for task\r\nperformance. When I contrasted this with variables less relevant to task performance (e.g.\r\nmovement direction), I did not observe differences in decoding quality over positions nor a\r\nreduction of dimensionality with learning.\r\nOverall, the largest changes in CA1 neural response with task learning happened in a\r\nmatter of a few trials; over days, changes undetectable in single-cell statistics were responsible\r\nfor re-structuring the hierarchy of neural representations at the population level; these changes\r\nwere task-specific and reflected different stages of learning. This indicates that complex task\r\nlearning may involve different magnitudes of response modulation in CA1, which happen at\r\nspecific time scales linked to behaviour." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Heloisa full_name: Chiossi, Heloisa id: 2BBA502C-F248-11E8-B48F-1D18A9856A87 last_name: Chiossi orcid: 0009-0004-2973-278X citation: ama: Chiossi HSC. Adaptive hierarchical representations in the hippocampus. 2024. doi:10.15479/at:ista:14821 apa: Chiossi, H. S. C. (2024). Adaptive hierarchical representations in the hippocampus. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:14821 chicago: Chiossi, Heloisa S. C. “Adaptive Hierarchical Representations in the Hippocampus.” Institute of Science and Technology Austria, 2024. https://doi.org/10.15479/at:ista:14821. ieee: H. S. C. Chiossi, “Adaptive hierarchical representations in the hippocampus,” Institute of Science and Technology Austria, 2024. ista: Chiossi HSC. 2024. Adaptive hierarchical representations in the hippocampus. Institute of Science and Technology Austria. mla: Chiossi, Heloisa S. C. Adaptive Hierarchical Representations in the Hippocampus. Institute of Science and Technology Austria, 2024, doi:10.15479/at:ista:14821. short: H.S.C. Chiossi, Adaptive Hierarchical Representations in the Hippocampus, Institute of Science and Technology Austria, 2024. corr_author: '1' date_created: 2024-01-16T14:25:21Z date_published: 2024-01-19T00:00:00Z date_updated: 2026-04-07T13:21:56Z day: '19' ddc: - '570' degree_awarded: PhD department: - _id: GradSch - _id: JoCs doi: 10.15479/at:ista:14821 ec_funded: 1 file: - access_level: closed checksum: d3fa3de1abd5af5204c13e9d55375615 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: hchiossi date_created: 2024-01-19T11:04:05Z date_updated: 2025-01-19T23:30:04Z embargo_to: open_access file_id: '14838' file_name: PhD_Thesis_190124.docx file_size: 8656268 relation: source_file - access_level: open_access checksum: 13adc8dcfb5b6b18107f89f0a98fa8bd content_type: application/pdf creator: hchiossi date_created: 2024-01-19T11:03:59Z date_updated: 2025-01-19T23:30:04Z embargo: 2025-01-19 file_id: '14839' file_name: PhD_Thesis_190124.pdf file_size: 6567275 relation: main_file file_date_updated: 2025-01-19T23:30:04Z has_accepted_license: '1' language: - iso: eng month: '01' oa: 1 oa_version: Published Version page: '89' project: - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria status: public supervisor: - first_name: Jozsef L full_name: Csicsvari, Jozsef L id: 3FA14672-F248-11E8-B48F-1D18A9856A87 last_name: Csicsvari orcid: 0000-0002-5193-4036 title: Adaptive hierarchical representations in the hippocampus type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2024' ... --- OA_place: publisher OA_type: hybrid PlanS_conform: '1' _id: '14843' abstract: - lang: eng text: The coupling between Ca2+ channels and release sensors is a key factor defining the signaling properties of a synapse. However, the coupling nanotopography at many synapses remains unknown, and it is unclear how it changes during development. To address these questions, we examined coupling at the cerebellar inhibitory basket cell (BC)-Purkinje cell (PC) synapse. Biophysical analysis of transmission by paired recording and intracellular pipette perfusion revealed that the effects of exogenous Ca2+ chelators decreased during development, despite constant reliance of release on P/Q-type Ca2+ channels. Structural analysis by freeze-fracture replica labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked vesicles were only clustered at later developmental stages. Modeling suggested a developmental transformation from a more random to a more clustered coupling nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic transmission. acknowledged_ssus: - _id: EM-Fac - _id: PreCl - _id: M-Shop acknowledgement: We thank Drs. David DiGregorio and Erwin Neher for critically reading an earlier version of the manuscript, Ralf Schneggenburger for helpful discussions, Benjamin Suter and Katharina Lichter for support with image analysis, Chris Wojtan for advice on numerical solution of partial differential equations, Maria Reva for help with Ripley analysis, Alois Schlögl for programming, and Akari Hagiwara and Toshihisa Ohtsuka for anti-ELKS antibody. We are grateful to Florian Marr, Christina Altmutter, and Vanessa Zheden for excellent technical assistance and to Eleftheria Kralli-Beller for manuscript editing. This research was supported by the Scientific Services Units (SSUs) of ISTA (Electron Microscopy Facility, Preclinical Facility, and Machine Shop). The project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 692692), the Fonds zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award; P 36232-B), all to P.J., and a DOC fellowship of the Austrian Academy of Sciences to J.-J.C. article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: JingJing full_name: Chen, JingJing id: 2C4E65C8-F248-11E8-B48F-1D18A9856A87 last_name: Chen - first_name: Walter full_name: Kaufmann, Walter id: 3F99E422-F248-11E8-B48F-1D18A9856A87 last_name: Kaufmann orcid: 0000-0001-9735-5315 - first_name: Chong full_name: Chen, Chong id: 3DFD581A-F248-11E8-B48F-1D18A9856A87 last_name: Chen - first_name: Itaru full_name: Arai, Itaru id: 32A73F6C-F248-11E8-B48F-1D18A9856A87 last_name: Arai - first_name: Olena full_name: Kim, Olena id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87 last_name: Kim orcid: 0000-0003-2344-1039 - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 citation: ama: Chen J, Kaufmann W, Chen C, et al. Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. Neuron. 2024;112(5):755-771.e9. doi:10.1016/j.neuron.2023.12.002 apa: Chen, J., Kaufmann, W., Chen, C., Arai, itaru, Kim, O., Shigemoto, R., & Jonas, P. M. (2024). Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2023.12.002 chicago: Chen, JingJing, Walter Kaufmann, Chong Chen, itaru Arai, Olena Kim, Ryuichi Shigemoto, and Peter M Jonas. “Developmental Transformation of Ca2+ Channel-Vesicle Nanotopography at a Central GABAergic Synapse.” Neuron. Elsevier, 2024. https://doi.org/10.1016/j.neuron.2023.12.002. ieee: J. Chen et al., “Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse,” Neuron, vol. 112, no. 5. Elsevier, p. 755–771.e9, 2024. ista: Chen J, Kaufmann W, Chen C, Arai itaru, Kim O, Shigemoto R, Jonas PM. 2024. Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. Neuron. 112(5), 755–771.e9. mla: Chen, JingJing, et al. “Developmental Transformation of Ca2+ Channel-Vesicle Nanotopography at a Central GABAergic Synapse.” Neuron, vol. 112, no. 5, Elsevier, 2024, p. 755–771.e9, doi:10.1016/j.neuron.2023.12.002. short: J. Chen, W. Kaufmann, C. Chen, itaru Arai, O. Kim, R. Shigemoto, P.M. Jonas, Neuron 112 (2024) 755–771.e9. corr_author: '1' date_created: 2024-01-21T23:00:56Z date_published: 2024-03-06T00:00:00Z date_updated: 2026-08-29T22:30:33Z day: '06' ddc: - '570' department: - _id: PeJo - _id: EM-Fac - _id: RySh doi: 10.1016/j.neuron.2023.12.002 ec_funded: 1 external_id: isi: - '001202925700001' pmid: - '38215739' file: - access_level: open_access checksum: 30098b4f0209556ddfb3540a23d07ca5 content_type: application/pdf creator: dernst date_created: 2025-04-23T14:02:08Z date_updated: 2025-04-23T14:02:08Z file_id: '19614' file_name: 2024_Neuron_Chen.pdf file_size: 8192355 relation: main_file success: 1 file_date_updated: 2025-04-23T14:02:08Z has_accepted_license: '1' intvolume: ' 112' isi: 1 issue: '5' language: - iso: eng month: '03' oa: 1 oa_version: Published Version page: 755-771.e9 pmid: 1 project: - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glutamatergic synapse - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: Synaptic communication in neuronal microcircuits - _id: bd88be38-d553-11ed-ba76-81d5a70a6ef5 grant_number: P36232 name: Mechanisms of GABA release in hippocampal circuits - _id: 26B66A3E-B435-11E9-9278-68D0E5697425 grant_number: '25383' name: Development of nanodomain coupling between Ca2+ channels and release sensors at a central inhibitory synapse publication: Neuron publication_identifier: eissn: - 1097-4199 issn: - 0896-6273 publication_status: published publisher: Elsevier quality_controlled: '1' related_material: link: - description: News on ISTA Website relation: press_release url: https://ista.ac.at/en/news/synapses-brought-to-the-point/ record: - id: '15101' relation: dissertation_contains status: public scopus_import: '1' status: public title: Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 112 year: '2024' ... --- OA_place: publisher _id: '15101' abstract: - lang: eng text: "The coupling between presynaptic Ca2+ channels and release sensors is a key factor that\r\ndetermines speed and efficacy of synapse transmission. At some excitatory synapses,\r\nchannel–sensor coupling becomes tighter during development, and tightening is often\r\nassociated with a switch in the reliance on different Ca2+ channel subtypes. However, the\r\ncoupling topography at many synapses remains unknown, and it is unclear how it changes\r\nduring development. To address this question, we analyzed the coupling configuration at the\r\ncerebellar basket cell (BC) to Purkinje cell (PC) synapse at different developmental stages,\r\ncombining biophysical analysis, structural analysis, and modeling.\r\nQuantal analysis of BC–PC indicated that release probability decreased, while the\r\nnumber of functional sites increased during development. Although transmitter release\r\npersistently relied on P/Q-type Ca2+ channels in the time period postnatal day 7–23, effects\r\nof the Ca2+ chelator EGTA and BAPTA applied by intracellular pipette perfusion decreased\r\nduring development, indicative of tightening of source-sensor coupling. Furthermore,\r\npresynaptic action potentials became shorter during development, suggesting reduced\r\nefficacy of Ca2+ channel activation.\r\nStructural analysis by freeze-fracture replica labeling (FRL) and transmission electron\r\nmicroscopy (EM) indicated that presynaptic P/Q-type Ca2+ channels formed nanoclusters\r\nthroughout development, whereas docked vesicles were only clustered at later\r\ndevelopmental stages. The number of functional release sites correlated better with the AZ\r\nnumber early in development, but match better with the Ca2+ channel cluster number at later\r\nstages.\r\nModeling suggested a developmental transformation from a more random to a more\r\nclustered coupling nanotopography. Thus, presynaptic signaling developmentally approaches\r\na point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic\r\ntransmission." acknowledged_ssus: - _id: EM-Fac alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: JingJing full_name: Chen, JingJing id: 2C4E65C8-F248-11E8-B48F-1D18A9856A87 last_name: Chen citation: ama: Chen J. Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse. 2024. doi:10.15479/at:ista:15101 apa: Chen, J. (2024). Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:15101 chicago: Chen, JingJing. “Developmental Transformation of Nanodomain Coupling between Ca2+ Channels and Release Sensors at a Central GABAergic Synapse.” Institute of Science and Technology Austria, 2024. https://doi.org/10.15479/at:ista:15101. ieee: J. Chen, “Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse,” Institute of Science and Technology Austria, 2024. ista: Chen J. 2024. Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse. Institute of Science and Technology Austria. mla: Chen, JingJing. Developmental Transformation of Nanodomain Coupling between Ca2+ Channels and Release Sensors at a Central GABAergic Synapse. Institute of Science and Technology Austria, 2024, doi:10.15479/at:ista:15101. short: J. Chen, Developmental Transformation of Nanodomain Coupling between Ca2+ Channels and Release Sensors at a Central GABAergic Synapse, Institute of Science and Technology Austria, 2024. corr_author: '1' date_created: 2024-03-11T10:09:54Z date_published: 2024-03-11T00:00:00Z date_updated: 2026-04-07T13:24:22Z day: '11' ddc: - '570' degree_awarded: PhD department: - _id: GradSch - _id: PeJo doi: 10.15479/at:ista:15101 ec_funded: 1 file: - access_level: closed checksum: db4947474ffa271e66c254b6fe876a55 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: jchen date_created: 2024-03-11T14:10:58Z date_updated: 2024-04-02T22:30:03Z embargo_to: open_access file_id: '15104' file_name: Thesis_Jingjing CHEN.docx file_size: 11271363 relation: source_file - access_level: open_access checksum: a5eeae8b5702cd540f5d03469bc33dde content_type: application/pdf creator: jchen date_created: 2024-03-11T14:11:06Z date_updated: 2024-04-02T22:30:03Z embargo: 2024-04-01 file_id: '15105' file_name: Thesis_Jingjing CHEN_merged.pdf file_size: 16627311 relation: main_file file_date_updated: 2024-04-02T22:30:03Z has_accepted_license: '1' language: - iso: eng month: '03' oa: 1 oa_version: Published Version page: '84' project: - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glutamatergic synapse - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: Synaptic communication in neuronal microcircuits - _id: bd88be38-d553-11ed-ba76-81d5a70a6ef5 grant_number: P36232 name: Mechanisms of GABA release in hippocampal circuits - _id: 26B66A3E-B435-11E9-9278-68D0E5697425 grant_number: '25383' name: Development of nanodomain coupling between Ca2+ channels and release sensors at a central inhibitory synapse publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '14843' relation: part_of_dissertation status: public status: public supervisor: - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 title: Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2024' ... --- OA_place: publisher _id: '18471' abstract: - lang: eng text: "Spatial omics technologies are enriching our understanding of complex biological samples, by\r\nallowing us to study their molecular composition while preserving the spatial relationships\r\nbetween molecules in their native context. As the field continues to advance, there are\r\ntechnical challenges that need to be addressed in order to take full advantage of the spatial\r\ncapabilities of these methods. In this work, I present two technical developments that I\r\nestablished for multiplexed error robust FISH (MERFISH) throughout my PhD: (1) pushing the\r\nspatial resolution limits to the nanoscale, and (2) adding rich tissue context to the mouse brain\r\ntranscriptome. To achieve nanoscale resolution with MERFISH in cultured cells, I combined it\r\nwith stimulated emission depletion (STED) and expansion microscopy (ExM) to achieve a\r\nspatial resolution as low as ~20 nm, and explored the compatibility of MERFISH with singlemolecule localization microscopy (SMLM) techniques. To visualize targeted mRNAs in mouse\r\nbrain tissue, I applied the comprehensive analysis of tissues across scales (CATS) toolbox, which\r\nprovides an unbiased morphological readout by labeling the extracellular domain. I\r\nsuccessfully established this method, which we call CATS-MERFISH-ExM, to work with thick\r\nmouse brain slices, being able to extract transcriptomics information with 3D tissue context.\r\nCATS-MERFISH-ExM enabled us to identify cell types and further visualize the subcellular\r\ndistribution of transcripts in mouse brain tissue, shedding light on the neuropil-specific\r\ntranscriptome. This method provides integrated information on cellular structure and\r\ntranscriptomes in situ, and could potentially be applied with other modalities, opening new\r\navenues for scientific discovery. " acknowledged_ssus: - _id: Bio - _id: LifeSc - _id: PreCl - _id: M-Shop - _id: ScienComp alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Nathalie full_name: Agudelo Duenas, Nathalie id: 40E7F008-F248-11E8-B48F-1D18A9856A87 last_name: Agudelo Duenas citation: ama: Agudelo Duenas N. Visualizing the neuronal transcriptional landscape with tissue context. 2024. doi:10.15479/at:ista:18471 apa: Agudelo Duenas, N. (2024). Visualizing the neuronal transcriptional landscape with tissue context. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:18471 chicago: Agudelo Duenas, Nathalie. “Visualizing the Neuronal Transcriptional Landscape with Tissue Context.” Institute of Science and Technology Austria, 2024. https://doi.org/10.15479/at:ista:18471. ieee: N. Agudelo Duenas, “Visualizing the neuronal transcriptional landscape with tissue context,” Institute of Science and Technology Austria, 2024. ista: Agudelo Duenas N. 2024. Visualizing the neuronal transcriptional landscape with tissue context. Institute of Science and Technology Austria. mla: Agudelo Duenas, Nathalie. Visualizing the Neuronal Transcriptional Landscape with Tissue Context. Institute of Science and Technology Austria, 2024, doi:10.15479/at:ista:18471. short: N. Agudelo Duenas, Visualizing the Neuronal Transcriptional Landscape with Tissue Context, Institute of Science and Technology Austria, 2024. corr_author: '1' date_created: 2024-10-26T20:02:42Z date_published: 2024-10-28T00:00:00Z date_updated: 2026-04-14T08:34:37Z day: '28' ddc: - '570' degree_awarded: PhD department: - _id: GradSch - _id: JoDa doi: 10.15479/at:ista:18471 ec_funded: 1 file: - access_level: closed checksum: 6d7c7725d040d8debc070dcb35ac965d content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: nagudelo date_created: 2024-10-26T22:29:06Z date_updated: 2025-05-05T22:30:04Z embargo_to: open_access file_id: '18475' file_name: PhD_thesis_Nathalie_Agudelo_Duenas_ISTA_final.docx file_size: 183077763 relation: source_file - access_level: open_access checksum: 52f9c0bf2bdafa3baf827b73814a53ff content_type: application/pdf creator: nagudelo date_created: 2024-10-26T23:13:33Z date_updated: 2025-05-05T22:30:04Z embargo: 2025-05-05 file_id: '18476' file_name: PhD_thesis_Nathalie_Agudelo_Duenas_ISTA_final.pdf file_size: 47027710 relation: main_file file_date_updated: 2025-05-05T22:30:04Z has_accepted_license: '1' language: - iso: eng month: '10' oa: 1 oa_version: Published Version page: '97' project: - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program - _id: 2548AE96-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232 name: Molecular Drug Targets publication_identifier: isbn: - 978-3-99078-044-2 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria status: public supervisor: - first_name: Johann G full_name: Danzl, Johann G id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87 last_name: Danzl orcid: 0000-0001-8559-3973 title: Visualizing the neuronal transcriptional landscape with tissue context tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2024' ... --- OA_embargo: '12' OA_place: publisher _id: '18574' abstract: - lang: eng text: "Biological vision is unlike a camera; rather than transmitting light information faithfully, early\r\nvisual circuits process the visual scene to convey only the relevant information in an efficient\r\nmanner. Consequentially, the nature of this visual processing then depends on what is the\r\nrelevant information in a scene and on the notion of efficiency. In this work, I study how visual\r\nprocessing is modulated by two different variations in the visual scene. First, I discovered that\r\nin the mouse (Mus musculus) retina, Retinal Ganglion Cells in the upper and lower visual\r\nfield have differences in the center surround structure of their receptive fields. Comparison\r\nwith models of efficient coding show that this adaptation likely evolved to cope with the\r\nbrightness gradient from the sky to the ground that is pervasive in natural scenes. In the\r\nsecond project, I study how the downstream neurons in the Superior Colliculus dynamically\r\nchange their temporal selectivity depending on the ambient luminance and behavioral state.\r\nAs the scene gets darker or when the animal is is less aroused, the neuronal responses get\r\nlaggier, while still maintaining their relative timing with respect to the population. Overall, this\r\nwork emphasises the need to understand visual processing in the context of specific demands\r\nof the animal in its the environment. The adaptive changes in the visual system, from the\r\nretinal ganglion cells to the superior colliculus, highlight the intricate ways in which biological\r\nvision optimizes the processing of visual information.\r\n" acknowledged_ssus: - _id: Bio - _id: ScienComp - _id: PreCl - _id: LifeSc - _id: M-Shop - _id: E-Lib acknowledgement: "This work would have been impossible without the Scientific Service Units of IST Austria. The resources and expertise provided by Scientific Computing (especially Alois Schlögl), the MIBA Machine Shop (especially Todor Asenov), the Preclinical Facility (especially Freyja Langer), the Library, the Lab Support Facility and the Imaging and Optics Facility were the essential bedrock I could build upon. I would also like to thank IT support at ISTA for powering through remote work and a cyberattack.\r\nI am grateful for having been funded initially by the European Union Horizon 2020 Marie Skłodowska-Curie grant 665385 and later by Prof. Maximilian Joesch's the European Research Council Starting (756502) and Consolidator (101086580) Grants." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Divyansh full_name: Gupta, Divyansh id: 2A485EBE-F248-11E8-B48F-1D18A9856A87 last_name: Gupta orcid: 0000-0001-7400-6665 citation: ama: Gupta D. Visual adaptations to natural statistics. 2024. doi:10.15479/at:ista:18574 apa: Gupta, D. (2024). Visual adaptations to natural statistics. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:18574 chicago: Gupta, Divyansh. “Visual Adaptations to Natural Statistics.” Institute of Science and Technology Austria, 2024. https://doi.org/10.15479/at:ista:18574. ieee: D. Gupta, “Visual adaptations to natural statistics,” Institute of Science and Technology Austria, 2024. ista: Gupta D. 2024. Visual adaptations to natural statistics. Institute of Science and Technology Austria. mla: Gupta, Divyansh. Visual Adaptations to Natural Statistics. Institute of Science and Technology Austria, 2024, doi:10.15479/at:ista:18574. short: D. Gupta, Visual Adaptations to Natural Statistics, Institute of Science and Technology Austria, 2024. corr_author: '1' date_created: 2024-11-20T21:30:44Z date_published: 2024-11-22T00:00:00Z date_updated: 2026-04-07T13:24:48Z day: '22' ddc: - '573' degree_awarded: PhD department: - _id: GradSch - _id: MaJö doi: 10.15479/at:ista:18574 ec_funded: 1 file: - access_level: closed checksum: ebb000d361c36b22ed6e639a931c6b7c content_type: application/zip creator: dgupta date_created: 2024-11-25T14:44:03Z date_updated: 2025-11-11T23:30:02Z embargo_to: open_access file_id: '18589' file_name: PhD Thesis - Divyansh Gupta.zip file_size: 75512262 relation: source_file - access_level: open_access checksum: 1282401eb71598bc311058b0fcefc6a1 content_type: application/pdf creator: dgupta date_created: 2024-11-26T11:43:19Z date_updated: 2025-11-11T23:30:02Z embargo: 2025-11-11 file_id: '18591' file_name: PDFA_PhD_Thesis___Divyansh_Gupta-26_11_24.pdf file_size: 6412619 relation: main_file file_date_updated: 2025-11-11T23:30:02Z has_accepted_license: '1' language: - iso: eng month: '11' oa: 1 oa_version: Published Version page: '86' project: - _id: bdaf81a8-d553-11ed-ba76-c95961984540 grant_number: '101086580' name: 'Action Selection in the Midbrain: Neuromodulation of Visuomotor Senses' - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program - _id: 2634E9D2-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '756502' name: Circuits of Visual Attention publication_identifier: isbn: - 978-3-99078-050-3 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '12349' relation: part_of_dissertation status: public - id: '12370' relation: research_data status: public status: public supervisor: - first_name: Maximilian A full_name: Jösch, Maximilian A id: 2BD278E6-F248-11E8-B48F-1D18A9856A87 last_name: Jösch orcid: 0000-0002-3937-1330 title: Visual adaptations to natural statistics tmp: image: /images/cc_by_nc_sa.png legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) short: CC BY-NC-SA (4.0) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2024' ... --- _id: '15323' abstract: - lang: eng text: Supercomplexes of the respiratory chain are established constituents of the oxidative phosphorylation system, but their role in mammalian metabolism has been hotly debated. Although recent studies have shown that different tissues/organs are equipped with specific sets of supercomplexes, depending on their metabolic needs, the notion that supercomplexes have a role in the regulation of metabolism has been challenged. However, irrespective of the mechanistic conclusions, the composition of various high molecular weight supercomplexes remains uncertain. Here, using cryogenic electron microscopy, we demonstrate that mammalian (mouse) tissues contain three defined types of ‘respirasome’, supercomplexes made of CI, CIII2 and CIV. The stoichiometry and position of CIV differs in the three respirasomes, of which only one contains the supercomplex-associated factor SCAF1, whose involvement in respirasome formation has long been contended. Our structures confirm that the ‘canonical’ respirasome (the C-respirasome, CICIII2CIV) does not contain SCAF1, which is instead associated to a different respirasome (the CS-respirasome), containing a second copy of CIV. We also identify an alternative respirasome (A-respirasome), with CIV bound to the ‘back’ of CI, instead of the ‘toe’. This structural characterization of mouse mitochondrial supercomplexes allows us to hypothesize a mechanistic basis for their specific role in different metabolic conditions. acknowledged_ssus: - _id: EM-Fac - _id: LifeSc - _id: PreCl - _id: ScienComp acknowledgement: Supercomplexes of the respiratory chain are established constituents of the oxidative phosphorylation system, but their role in mammalian metabolism has been hotly debated. Although recent studies have shown that different tissues/organs are equipped with specific sets of supercomplexes, depending on their metabolic needs, the notion that supercomplexes have a role in the regulation of metabolism has been challenged. However, irrespective of the mechanistic conclusions, the composition of various high molecular weight supercomplexes remains uncertain. Here, using cryogenic electron microscopy, we demonstrate that mammalian (mouse) tissues contain three defined types of ‘respirasome’, supercomplexes made of CI, CIII2 and CIV. The stoichiometry and position of CIV differs in the three respirasomes, of which only one contains the supercomplex-associated factor SCAF1, whose involvement in respirasome formation has long been contended. Our structures confirm that the ‘canonical’ respirasome (the C-respirasome, CICIII2CIV) does not contain SCAF1, which is instead associated to a different respirasome (the CS-respirasome), containing a second copy of CIV. We also identify an alternative respirasome (A-respirasome), with CIV bound to the ‘back’ of CI, instead of the ‘toe’. This structural characterization of mouse mitochondrial supercomplexes allows us to hypothesize a mechanistic basis for their specific role in different metabolic conditions. article_processing_charge: No article_type: original author: - first_name: Irene full_name: Vercellino, Irene id: 3ED6AF16-F248-11E8-B48F-1D18A9856A87 last_name: Vercellino orcid: 0000-0001-5618-3449 - first_name: Leonid A full_name: Sazanov, Leonid A id: 338D39FE-F248-11E8-B48F-1D18A9856A87 last_name: Sazanov orcid: 0000-0002-0977-7989 citation: ama: Vercellino I, Sazanov LA. SCAF1 drives the compositional diversity of mammalian respirasomes. Nature Structural and Molecular Biology. 2024;31:1061-1071. doi:10.1038/s41594-024-01255-0 apa: Vercellino, I., & Sazanov, L. A. (2024). SCAF1 drives the compositional diversity of mammalian respirasomes. Nature Structural and Molecular Biology. Springer Nature. https://doi.org/10.1038/s41594-024-01255-0 chicago: Vercellino, Irene, and Leonid A Sazanov. “SCAF1 Drives the Compositional Diversity of Mammalian Respirasomes.” Nature Structural and Molecular Biology. Springer Nature, 2024. https://doi.org/10.1038/s41594-024-01255-0. ieee: I. Vercellino and L. A. Sazanov, “SCAF1 drives the compositional diversity of mammalian respirasomes,” Nature Structural and Molecular Biology, vol. 31. Springer Nature, pp. 1061–1071, 2024. ista: Vercellino I, Sazanov LA. 2024. SCAF1 drives the compositional diversity of mammalian respirasomes. Nature Structural and Molecular Biology. 31, 1061–1071. mla: Vercellino, Irene, and Leonid A. Sazanov. “SCAF1 Drives the Compositional Diversity of Mammalian Respirasomes.” Nature Structural and Molecular Biology, vol. 31, Springer Nature, 2024, pp. 1061–71, doi:10.1038/s41594-024-01255-0. short: I. Vercellino, L.A. Sazanov, Nature Structural and Molecular Biology 31 (2024) 1061–1071. corr_author: '1' date_created: 2024-04-14T22:01:03Z date_published: 2024-07-01T00:00:00Z date_updated: 2025-11-24T08:35:04Z day: '01' ddc: - '572' department: - _id: LeSa doi: 10.1038/s41594-024-01255-0 ec_funded: 1 external_id: isi: - '001196897300001' pmid: - '38575788' file: - access_level: open_access checksum: 21f05d188762acd7f49a97f3d09c8d9f content_type: application/pdf creator: lsazanov date_created: 2024-05-14T11:57:56Z date_updated: 2025-01-01T23:30:03Z embargo: 2025-01-01 file_id: '15392' file_name: megacomplex_submit_NSMB_withFigures.pdf file_size: 24424729 relation: main_file file_date_updated: 2025-01-01T23:30:03Z has_accepted_license: '1' intvolume: ' 31' isi: 1 language: - iso: eng month: '07' oa: 1 oa_version: Submitted Version page: 1061-1071 pmid: 1 project: - _id: 627abdeb-2b32-11ec-9570-ec31a97243d3 call_identifier: H2020 grant_number: '101020697' name: Structure and mechanism of respiratory chain molecular machines publication: Nature Structural and Molecular Biology publication_identifier: eissn: - 1545-9985 issn: - 1545-9993 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - relation: erratum url: https://doi.org/10.1038/s41594-025-01721-3 scopus_import: '1' status: public title: SCAF1 drives the compositional diversity of mammalian respirasomes tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 31 year: '2024' ... --- APC_amount: 5887,8 EUR OA_place: publisher OA_type: hybrid _id: '15084' abstract: - lang: eng text: "GABAB receptor (GBR) activation inhibits neurotransmitter release in axon terminals in the brain, except in medial habenula (MHb) terminals, which show robust potentiation. However, mechanisms underlying this enigmatic potentiation remain elusive. Here, we report that GBR activation on MHb terminals induces an activity-dependent transition from a facilitating, tonic to a depressing, phasic neurotransmitter release mode. This transition is accompanied by a 4.1-fold increase in readily releasable vesicle pool (RRP) size and a 3.5-fold increase of docked synaptic vesicles (SVs) at the presynaptic active zone (AZ). Strikingly, the depressing phasic release exhibits looser coupling distance than the tonic release. Furthermore, the tonic and phasic release are selectively affected by deletion of synaptoporin (SPO) and Ca\r\n 2+\r\n -dependent activator protein for secretion 2 (CAPS2), respectively. SPO modulates augmentation, the short-term plasticity associated with tonic release, and CAPS2 retains the increased RRP for initial responses in phasic response trains. The cytosolic protein CAPS2 showed a SV-associated distribution similar to the vesicular transmembrane protein SPO, and they were colocalized in the same terminals. We developed the “Flash and Freeze-fracture” method, and revealed the release of SPO-associated vesicles in both tonic and phasic modes and activity-dependent recruitment of CAPS2 to the AZ during phasic release, which lasted several minutes. Overall, these results indicate that GBR activation translocates CAPS2 to the AZ along with the fusion of CAPS2-associated SVs, contributing to persistency of the RRP increase. Thus, we identified structural and molecular mechanisms underlying tonic and phasic neurotransmitter release and their transition by GBR activation in MHb terminals." acknowledged_ssus: - _id: M-Shop - _id: PreCl - _id: EM-Fac acknowledgement: We thank Erwin Neher and Ipe Ninan for critical comments on the manuscript. This project has received funding from the European Research Council (ERC) and European Commission, under the European Union’s Horizon 2020 research and innovation program (ERC grant agreement no. 694539 to R.S. and the Marie Skłodowska-Curie grant agreement no. 665385 to C.Ö.). This study was supported by the Cooperative Study Program of Center for Animal Resources and Collaborative Study of NINS. We thank Kohgaku Eguchi for statistical analysis, Yu Kasugai for additional EM imaging, Robert Beattie for the design of the slice recovery chamber for Flash and Freeze experiments, Todor Asenov from the ISTA machine shop for custom part preparations for high-pressure freezing, the ISTA preclinical facility for animal caretaking, and the ISTA EM facilities for technical support. article_number: e2301449121 article_processing_charge: Yes (in subscription journal) article_type: original author: - first_name: Peter full_name: Koppensteiner, Peter id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87 last_name: Koppensteiner orcid: 0000-0002-3509-1948 - first_name: Pradeep full_name: Bhandari, Pradeep id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87 last_name: Bhandari orcid: 0000-0003-0863-4481 - first_name: Hüseyin C full_name: Önal, Hüseyin C id: 4659D740-F248-11E8-B48F-1D18A9856A87 last_name: Önal orcid: 0000-0002-2771-2011 - first_name: Carolina full_name: Borges Merjane, Carolina id: 4305C450-F248-11E8-B48F-1D18A9856A87 last_name: Borges Merjane orcid: 0000-0003-0005-401X - first_name: Elodie full_name: Le Monnier, Elodie id: 3B59276A-F248-11E8-B48F-1D18A9856A87 last_name: Le Monnier - first_name: Utsa full_name: Roy, Utsa id: 4d26cf11-5355-11ee-ae5a-eb05e255b9b2 last_name: Roy - first_name: Yukihiro full_name: Nakamura, Yukihiro last_name: Nakamura - first_name: Tetsushi full_name: Sadakata, Tetsushi last_name: Sadakata - first_name: Makoto full_name: Sanbo, Makoto last_name: Sanbo - first_name: Masumi full_name: Hirabayashi, Masumi last_name: Hirabayashi - first_name: JeongSeop full_name: Rhee, JeongSeop last_name: Rhee - first_name: Nils full_name: Brose, Nils last_name: Brose - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 citation: ama: Koppensteiner P, Bhandari P, Önal C, et al. GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles. Proceedings of the National Academy of Sciences of the United States of America. 2024;121(8). doi:10.1073/pnas.2301449121 apa: Koppensteiner, P., Bhandari, P., Önal, C., Borges Merjane, C., Le Monnier, E., Roy, U., … Shigemoto, R. (2024). GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles. Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences. https://doi.org/10.1073/pnas.2301449121 chicago: Koppensteiner, Peter, Pradeep Bhandari, Cihan Önal, Carolina Borges Merjane, Elodie Le Monnier, Utsa Roy, Yukihiro Nakamura, et al. “GABAB Receptors Induce Phasic Release from Medial Habenula Terminals through Activity-Dependent Recruitment of Release-Ready Vesicles.” Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences, 2024. https://doi.org/10.1073/pnas.2301449121. ieee: P. Koppensteiner et al., “GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles,” Proceedings of the National Academy of Sciences of the United States of America, vol. 121, no. 8. National Academy of Sciences, 2024. ista: Koppensteiner P, Bhandari P, Önal C, Borges Merjane C, Le Monnier E, Roy U, Nakamura Y, Sadakata T, Sanbo M, Hirabayashi M, Rhee J, Brose N, Jonas PM, Shigemoto R. 2024. GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles. Proceedings of the National Academy of Sciences of the United States of America. 121(8), e2301449121. mla: Koppensteiner, Peter, et al. “GABAB Receptors Induce Phasic Release from Medial Habenula Terminals through Activity-Dependent Recruitment of Release-Ready Vesicles.” Proceedings of the National Academy of Sciences of the United States of America, vol. 121, no. 8, e2301449121, National Academy of Sciences, 2024, doi:10.1073/pnas.2301449121. short: P. Koppensteiner, P. Bhandari, C. Önal, C. Borges Merjane, E. Le Monnier, U. Roy, Y. Nakamura, T. Sadakata, M. Sanbo, M. Hirabayashi, J. Rhee, N. Brose, P.M. Jonas, R. Shigemoto, Proceedings of the National Academy of Sciences of the United States of America 121 (2024). corr_author: '1' date_created: 2024-03-05T09:23:55Z date_published: 2024-02-20T00:00:00Z date_updated: 2026-08-29T22:30:37Z day: '20' ddc: - '570' department: - _id: RySh - _id: PeJo doi: 10.1073/pnas.2301449121 ec_funded: 1 external_id: isi: - '001208567300006' pmid: - '38346189' file: - access_level: open_access checksum: b25b2a057c266ff317a48b0d54d6fc8a content_type: application/pdf creator: dernst date_created: 2024-03-12T13:42:42Z date_updated: 2024-03-12T13:42:42Z file_id: '15110' file_name: 2024_PNAS_Koppensteiner.pdf file_size: 13648221 relation: main_file success: 1 file_date_updated: 2024-03-12T13:42:42Z has_accepted_license: '1' intvolume: ' 121' isi: 1 issue: '8' language: - iso: eng month: '02' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 25CA28EA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '694539' name: 'In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour' - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program publication: Proceedings of the National Academy of Sciences of the United States of America publication_identifier: eissn: - 1091-6490 issn: - 0027-8424 publication_status: published publisher: National Academy of Sciences quality_controlled: '1' related_material: link: - description: News on ISTA Website relation: press_release url: https://ista.ac.at/en/news/neuronal-insights-flash-and-freeze-fracture/ record: - id: '13173' relation: research_data status: public - id: '19271' relation: dissertation_contains status: public scopus_import: '1' status: public title: GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 121 year: '2024' ... --- OA_place: publisher OA_type: hybrid _id: '17148' abstract: - lang: eng text: During neural tube (NT) development, the notochord induces an organizer, the floorplate, which secretes Sonic Hedgehog (SHH) to pattern neural progenitors. Conversely, NT organoids (NTOs) from embryonic stem cells (ESCs) spontaneously form floorplates without the notochord, demonstrating that stem cells can self-organize without embryonic inducers. Here, we investigated floorplate self-organization in clonal mouse NTOs. Expression of the floorplate marker FOXA2 was initially spatially scattered before resolving into multiple clusters, which underwent competition and sorting, resulting in a stable “winning” floorplate. We identified that BMP signaling governed long-range cluster competition. FOXA2+ clusters expressed BMP4, suppressing FOXA2 in receiving cells while simultaneously expressing the BMP-inhibitor NOGGIN, promoting cluster persistence. Noggin mutation perturbed floorplate formation in NTOs and in the NT in vivo at mid/hindbrain regions, demonstrating how the floorplate can form autonomously without the notochord. Identifying the pathways governing organizer self-organization is critical for harnessing the developmental plasticity of stem cells in tissue engineering. acknowledgement: We thank P. Pasierbek, A.C. Moreno, T. Lendl, and K. Aumayr for microscopy support; G. Schmauss for FACS support; M. Novatchkova for assistance with Bioinformatic analyses; J. Ahel, A. Polikarpova, S. Horer, E. Cesare, and E. Norouzi for technical assistance; A. Meinhardt for supervision; DRESDEN-concept Genome Center, A. Vogt, A. Sommer, and the Vienna BioCenter NGS facility for RNA sequencing. We are grateful to M. Placzek and E. Martí for discussions about the floorplate; to S. Shvartsman for valuable input; to A. Aszodi, W. Masselink, and S. Raiders for advice on statistical analyses; to J. Cornwall Scoones, G. Martello, and Tanaka lab members for critical reading of the manuscript; E. Bassat and E. Chatzidaki for contributing schematics; and to K. Lust for support. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement ERC AdG 742046) to E.M.T. This research was funded in whole or in part by the Austrian Science Fund (FWF) (10.55776/F7803-B) (Stem Cell Modulation) to E.M.T. and A.K., Sir Henry Wellcome postdoctoral fellowship to H.T.S., ELBE fellowship to K.I., and National Science Foundation (US) Phy 2013131 to E.S. The A.K. lab is also supported by ISTA and the European Research Council under Horizon Europe grant 101044579, and S.L. is supported by Gesellschaft für Forschungsförderung Niederösterreich m.b.H. fellowship SC19-011. This work was supported in part by the Francis Crick Institute, which receives its core funding from Cancer Research UK (CC001051), the UK Medical Research Council (CC001051), and the Wellcome Trust (CC001051). For the purpose of open access, the authors have applied a CC BY public copyright license to any author accepted manuscript (AAM) version arising from this submission. article_processing_charge: Yes (in subscription journal) article_type: original author: - first_name: Teresa full_name: Krammer, Teresa last_name: Krammer - first_name: Hannah T. full_name: Stuart, Hannah T. last_name: Stuart - first_name: Elena full_name: Gromberg, Elena last_name: Gromberg - first_name: Keisuke full_name: Ishihara, Keisuke last_name: Ishihara - first_name: Dillon full_name: Cislo, Dillon last_name: Cislo - first_name: Manuela full_name: Melchionda, Manuela last_name: Melchionda - first_name: Fernando full_name: Becerril Perez, Fernando last_name: Becerril Perez - first_name: Jingkui full_name: Wang, Jingkui last_name: Wang - first_name: Elena full_name: Costantini, Elena last_name: Costantini - first_name: Stefanie full_name: Rus, Stefanie id: 4D9EC9B6-F248-11E8-B48F-1D18A9856A87 last_name: Rus orcid: 0000-0001-8703-1093 - first_name: Laura full_name: Arbanas, Laura last_name: Arbanas - first_name: Alexandra full_name: Hörmann, Alexandra last_name: Hörmann - first_name: Ralph A. full_name: Neumüller, Ralph A. last_name: Neumüller - first_name: Nicola full_name: Elvassore, Nicola last_name: Elvassore - first_name: Eric full_name: Siggia, Eric last_name: Siggia - first_name: James full_name: Briscoe, James last_name: Briscoe - first_name: Anna full_name: Kicheva, Anna id: 3959A2A0-F248-11E8-B48F-1D18A9856A87 last_name: Kicheva orcid: 0000-0003-4509-4998 - first_name: Elly M. full_name: Tanaka, Elly M. last_name: Tanaka citation: ama: Krammer T, Stuart HT, Gromberg E, et al. Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition. Developmental Cell. 2024;59(15):1940-1953.e10. doi:10.1016/j.devcel.2024.04.021 apa: Krammer, T., Stuart, H. T., Gromberg, E., Ishihara, K., Cislo, D., Melchionda, M., … Tanaka, E. M. (2024). Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition. Developmental Cell. Elsevier. https://doi.org/10.1016/j.devcel.2024.04.021 chicago: Krammer, Teresa, Hannah T. Stuart, Elena Gromberg, Keisuke Ishihara, Dillon Cislo, Manuela Melchionda, Fernando Becerril Perez, et al. “Mouse Neural Tube Organoids Self-Organize Floorplate through BMP-Mediated Cluster Competition.” Developmental Cell. Elsevier, 2024. https://doi.org/10.1016/j.devcel.2024.04.021. ieee: T. Krammer et al., “Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition,” Developmental Cell, vol. 59, no. 15. Elsevier, p. 1940–1953.e10, 2024. ista: Krammer T, Stuart HT, Gromberg E, Ishihara K, Cislo D, Melchionda M, Becerril Perez F, Wang J, Costantini E, Rus S, Arbanas L, Hörmann A, Neumüller RA, Elvassore N, Siggia E, Briscoe J, Kicheva A, Tanaka EM. 2024. Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition. Developmental Cell. 59(15), 1940–1953.e10. mla: Krammer, Teresa, et al. “Mouse Neural Tube Organoids Self-Organize Floorplate through BMP-Mediated Cluster Competition.” Developmental Cell, vol. 59, no. 15, Elsevier, 2024, p. 1940–1953.e10, doi:10.1016/j.devcel.2024.04.021. short: T. Krammer, H.T. Stuart, E. Gromberg, K. Ishihara, D. Cislo, M. Melchionda, F. Becerril Perez, J. Wang, E. Costantini, S. Rus, L. Arbanas, A. Hörmann, R.A. Neumüller, N. Elvassore, E. Siggia, J. Briscoe, A. Kicheva, E.M. Tanaka, Developmental Cell 59 (2024) 1940–1953.e10. date_created: 2024-06-16T22:01:07Z date_published: 2024-08-01T00:00:00Z date_updated: 2026-08-29T22:30:39Z day: '01' ddc: - '570' department: - _id: AnKi doi: 10.1016/j.devcel.2024.04.021 external_id: isi: - '001289684800001' pmid: - '38776925' file: - access_level: open_access checksum: fefdea9c02862b4bb74de49b65ce638a content_type: application/pdf creator: dernst date_created: 2025-01-13T10:59:12Z date_updated: 2025-01-13T10:59:12Z file_id: '18841' file_name: 2024_DevelopmentalCell_Krammer.pdf file_size: 6249076 relation: main_file success: 1 file_date_updated: 2025-01-13T10:59:12Z has_accepted_license: '1' intvolume: ' 59' isi: 1 issue: '15' language: - iso: eng month: '08' oa: 1 oa_version: Published Version page: 1940-1953.e10 pmid: 1 project: - _id: bd7e737f-d553-11ed-ba76-d69ffb5ee3aa grant_number: '101044579' name: Mechanisms of tissue size regulation in spinal cord development - _id: 9B9B39FA-BA93-11EA-9121-9846C619BF3A grant_number: SC19-011 name: The regulatory logic of pattern formation in the vertebrate dorsal neural tube publication: Developmental Cell publication_identifier: eissn: - 1878-1551 issn: - 1534-5807 publication_status: published publisher: Elsevier quality_controlled: '1' related_material: record: - id: '19763' relation: dissertation_contains status: public scopus_import: '1' status: public title: Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 59 year: '2024' ... --- APC_amount: 804 EUR DOAJ_listed: '1' OA_place: publisher OA_type: gold _id: '18601' abstract: - lang: eng text: "Geometrically controlled stem cell differentiation promotes reproducible pattern formation. Here, we present a protocol to fabricate elastomeric stencils for patterned stem cell differentiation. We describe procedures for using photolithography to produce molds, followed by molding polydimethylsiloxane (PDMS) to obtain stencils with through holes. We then provide instructions for culturing cells on stencils and, finally, removing stencils to allow colony growth and cell migration. This approach yields reproducible two-dimensional organoids tailored for quantitative studies of growth and pattern formation.\r\nFor complete details on the use and execution of this protocol, please refer to Lehr et al.1" acknowledged_ssus: - _id: NanoFab acknowledgement: We thank the nanofabrication facility at ISTA for technical assistance. Work in the A.K. lab is supported by ISTA, the European Research Council under Horizon Europe (grant 101044579), and the Austrian Science Fund (FWF) (grant https://doi.org/10.55776/F78). S.L. is supported by Gesellschaft für Forschungsförderung Niederösterreich m.b.H. fellowship SC19-011. article_number: '103187' article_processing_charge: Yes article_type: original author: - first_name: Stefanie full_name: Rus, Stefanie id: 4D9EC9B6-F248-11E8-B48F-1D18A9856A87 last_name: Rus orcid: 0000-0001-8703-1093 - first_name: Jack full_name: Merrin, Jack id: 4515C308-F248-11E8-B48F-1D18A9856A87 last_name: Merrin orcid: 0000-0001-5145-4609 - first_name: Monika Aleksandra full_name: Kulig, Monika Aleksandra id: 3331f5ae-e896-11ec-af79-eeb79769bcb7 last_name: Kulig - first_name: Thomas full_name: Minchington, Thomas id: 7d1648cb-19e9-11eb-8e7a-f8c037fb3e3f last_name: Minchington - first_name: Anna full_name: Kicheva, Anna id: 3959A2A0-F248-11E8-B48F-1D18A9856A87 last_name: Kicheva orcid: 0000-0003-4509-4998 citation: ama: Rus S, Merrin J, Kulig MA, Minchington T, Kicheva A. Protocol for fabricating elastomeric stencils for patterned stem cell differentiation. STAR Protocols. 2024;5(4). doi:10.1016/j.xpro.2024.103187 apa: Rus, S., Merrin, J., Kulig, M. A., Minchington, T., & Kicheva, A. (2024). Protocol for fabricating elastomeric stencils for patterned stem cell differentiation. STAR Protocols. Elsevier. https://doi.org/10.1016/j.xpro.2024.103187 chicago: Rus, Stefanie, Jack Merrin, Monika Aleksandra Kulig, Thomas Minchington, and Anna Kicheva. “Protocol for Fabricating Elastomeric Stencils for Patterned Stem Cell Differentiation.” STAR Protocols. Elsevier, 2024. https://doi.org/10.1016/j.xpro.2024.103187. ieee: S. Rus, J. Merrin, M. A. Kulig, T. Minchington, and A. Kicheva, “Protocol for fabricating elastomeric stencils for patterned stem cell differentiation,” STAR Protocols, vol. 5, no. 4. Elsevier, 2024. ista: Rus S, Merrin J, Kulig MA, Minchington T, Kicheva A. 2024. Protocol for fabricating elastomeric stencils for patterned stem cell differentiation. STAR Protocols. 5(4), 103187. mla: Rus, Stefanie, et al. “Protocol for Fabricating Elastomeric Stencils for Patterned Stem Cell Differentiation.” STAR Protocols, vol. 5, no. 4, 103187, Elsevier, 2024, doi:10.1016/j.xpro.2024.103187. short: S. Rus, J. Merrin, M.A. Kulig, T. Minchington, A. Kicheva, STAR Protocols 5 (2024). corr_author: '1' date_created: 2024-12-01T23:01:53Z date_published: 2024-12-20T00:00:00Z date_updated: 2026-08-29T22:30:39Z day: '20' ddc: - '570' department: - _id: AnKi - _id: NanoFab doi: 10.1016/j.xpro.2024.103187 external_id: pmid: - '39602310' file: - access_level: open_access checksum: 0c61a6f9978608a103865905e06f4581 content_type: application/pdf creator: dernst date_created: 2024-12-03T10:53:23Z date_updated: 2024-12-03T10:53:23Z file_id: '18610' file_name: 2024_STARProtoc_Lehr.pdf file_size: 4989169 relation: main_file success: 1 file_date_updated: 2024-12-03T10:53:23Z has_accepted_license: '1' intvolume: ' 5' issue: '4' language: - iso: eng month: '12' oa: 1 oa_version: Published Version pmid: 1 project: - _id: bd7e737f-d553-11ed-ba76-d69ffb5ee3aa grant_number: '101044579' name: Mechanisms of tissue size regulation in spinal cord development - _id: 9B9B39FA-BA93-11EA-9121-9846C619BF3A grant_number: SC19-011 name: The regulatory logic of pattern formation in the vertebrate dorsal neural tube publication: STAR Protocols publication_identifier: eissn: - 2666-1667 publication_status: published publisher: Elsevier quality_controlled: '1' related_material: record: - id: '19763' relation: dissertation_contains status: public scopus_import: '1' status: public title: Protocol for fabricating elastomeric stencils for patterned stem cell differentiation tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 5 year: '2024' ... --- OA_place: repository OA_type: green _id: '14796' abstract: - lang: eng text: Key innovations are fundamental to biological diversification, but their genetic basis is poorly understood. A recent transition from egg-laying to live-bearing in marine snails (Littorina spp.) provides the opportunity to study the genetic architecture of an innovation that has evolved repeatedly across animals. Individuals do not cluster by reproductive mode in a genome-wide phylogeny, but local genealogical analysis revealed numerous small genomic regions where all live-bearers carry the same core haplotype. Candidate regions show evidence for live-bearer–specific positive selection and are enriched for genes that are differentially expressed between egg-laying and live-bearing reproductive systems. Ages of selective sweeps suggest that live-bearer–specific alleles accumulated over more than 200,000 generations. Our results suggest that new functions evolve through the recruitment of many alleles rather than in a single evolutionary step. acknowledgement: "We thank J. Galindo, M. Montaño-Rendón, N. Mikhailova, A. Blakeslee, E. Arnason, and P. Kemppainen for providing samples; R. Turney, G. Sotelo, J. Larsson, T. Broquet, and S. Loisel for help collecting samples; Science Animated for providing the snail cartoons shown in Fig. 1; M. Dunning for help in developing bioinformatic pipelines; R. Faria, H. Morales, and V. Sousa for advice; and M. Hahn, J. Slate, M. Ravinet, J. Raeymaekers, A. Comeault, and N. Barton for feedback on a draft manuscript.\r\nThis work was supported by the Natural Environment Research Council (grant NE/P001610/1 to R.K.B.), the European Research Council (grant ERC-2015-AdG693030-BARRIERS to R.K.B.), the Norwegian Research Council (RCN Project 315287 to A.M.W.), and the Swedish Research Council (grant 2020-05385 to E.L.)." article_processing_charge: No article_type: original author: - first_name: Sean full_name: Stankowski, Sean id: 43161670-5719-11EA-8025-FABC3DDC885E last_name: Stankowski - first_name: Zuzanna B. full_name: Zagrodzka, Zuzanna B. last_name: Zagrodzka - first_name: Martin D. full_name: Garlovsky, Martin D. last_name: Garlovsky - first_name: Arka full_name: Pal, Arka id: 6AAB2240-CA9A-11E9-9C1A-D9D1E5697425 last_name: Pal orcid: 0000-0002-4530-8469 - first_name: Daria full_name: Shipilina, Daria id: 428A94B0-F248-11E8-B48F-1D18A9856A87 last_name: Shipilina orcid: 0000-0002-1145-9226 - first_name: Diego Fernando full_name: Garcia Castillo, Diego Fernando id: ae681a14-dc74-11ea-a0a7-c6ef18161701 last_name: Garcia Castillo - first_name: Hila full_name: Lifchitz, Hila id: d6ab5470-2fb3-11ed-8633-986a9b84edac last_name: Lifchitz - first_name: Alan full_name: Le Moan, Alan last_name: Le Moan - first_name: Erica full_name: Leder, Erica last_name: Leder - first_name: James full_name: Reeve, James last_name: Reeve - first_name: Kerstin full_name: Johannesson, Kerstin last_name: Johannesson - first_name: Anja M full_name: Westram, Anja M id: 3C147470-F248-11E8-B48F-1D18A9856A87 last_name: Westram orcid: 0000-0003-1050-4969 - first_name: Roger K. full_name: Butlin, Roger K. last_name: Butlin citation: ama: Stankowski S, Zagrodzka ZB, Garlovsky MD, et al. The genetic basis of a recent transition to live-bearing in marine snails. Science. 2024;383(6678):114-119. doi:10.1126/science.adi2982 apa: Stankowski, S., Zagrodzka, Z. B., Garlovsky, M. D., Pal, A., Shipilina, D., Garcia Castillo, D. F., … Butlin, R. K. (2024). The genetic basis of a recent transition to live-bearing in marine snails. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.adi2982 chicago: Stankowski, Sean, Zuzanna B. Zagrodzka, Martin D. Garlovsky, Arka Pal, Daria Shipilina, Diego Fernando Garcia Castillo, Hila Lifchitz, et al. “The Genetic Basis of a Recent Transition to Live-Bearing in Marine Snails.” Science. American Association for the Advancement of Science, 2024. https://doi.org/10.1126/science.adi2982. ieee: S. Stankowski et al., “The genetic basis of a recent transition to live-bearing in marine snails,” Science, vol. 383, no. 6678. American Association for the Advancement of Science, pp. 114–119, 2024. ista: Stankowski S, Zagrodzka ZB, Garlovsky MD, Pal A, Shipilina D, Garcia Castillo DF, Lifchitz H, Le Moan A, Leder E, Reeve J, Johannesson K, Westram AM, Butlin RK. 2024. The genetic basis of a recent transition to live-bearing in marine snails. Science. 383(6678), 114–119. mla: Stankowski, Sean, et al. “The Genetic Basis of a Recent Transition to Live-Bearing in Marine Snails.” Science, vol. 383, no. 6678, American Association for the Advancement of Science, 2024, pp. 114–19, doi:10.1126/science.adi2982. short: S. Stankowski, Z.B. Zagrodzka, M.D. Garlovsky, A. Pal, D. Shipilina, D.F. Garcia Castillo, H. Lifchitz, A. Le Moan, E. Leder, J. Reeve, K. Johannesson, A.M. Westram, R.K. Butlin, Science 383 (2024) 114–119. corr_author: '1' date_created: 2024-01-14T23:00:56Z date_published: 2024-01-05T00:00:00Z date_updated: 2026-08-29T22:30:43Z day: '05' department: - _id: NiBa - _id: GradSch doi: 10.1126/science.adi2982 external_id: isi: - '001138156400003' pmid: - '38175895' intvolume: ' 383' isi: 1 issue: '6678' language: - iso: eng main_file_link: - open_access: '1' url: https://figshare.com/articles/journal_contribution/The_genetic_basis_of_a_recent_transition_to_live-bearing_in_marine_snails/26356054?file=47868241 month: '01' oa: 1 oa_version: Submitted Version page: 114-119 pmid: 1 publication: Science publication_identifier: eissn: - 1095-9203 publication_status: published publisher: American Association for the Advancement of Science quality_controlled: '1' related_material: link: - description: News on ISTA Website relation: press_release url: https://ista.ac.at/en/news/the-snail-or-the-egg/ record: - id: '14812' relation: research_data status: public - id: '20694' relation: dissertation_contains status: public scopus_import: '1' status: public title: The genetic basis of a recent transition to live-bearing in marine snails type: journal_article user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 383 year: '2024' ... --- DOAJ_listed: '1' OA_place: publisher OA_type: gold _id: '15009' abstract: - lang: eng text: Since the commercialization of brine shrimp (genus Artemia) in the 1950s, this lineage, and in particular the model species Artemia franciscana, has been the subject of extensive research. However, our understanding of the genetic mechanisms underlying various aspects of their reproductive biology, including sex determination, is still lacking. This is partly due to the scarcity of genomic resources for Artemia species and crustaceans in general. Here, we present a chromosome-level genome assembly of A. franciscana (Kellogg 1906), from the Great Salt Lake, United States. The genome is 1 GB, and the majority of the genome (81%) is scaffolded into 21 linkage groups using a previously published high-density linkage map. We performed coverage and FST analyses using male and female genomic and transcriptomic reads to quantify the extent of differentiation between the Z and W chromosomes. Additionally, we quantified the expression levels in male and female heads and gonads and found further evidence for dosage compensation in this species. article_number: evae006 article_processing_charge: Yes article_type: original author: - first_name: Vincent K full_name: Bett, Vincent K id: 57854184-AAE0-11E9-8D04-98D6E5697425 last_name: Bett - first_name: Ariana full_name: Macon, Ariana id: 2A0848E2-F248-11E8-B48F-1D18A9856A87 last_name: Macon - first_name: Beatriz full_name: Vicoso, Beatriz id: 49E1C5C6-F248-11E8-B48F-1D18A9856A87 last_name: Vicoso orcid: 0000-0002-4579-8306 - first_name: Marwan N full_name: Elkrewi, Marwan N id: 0B46FACA-A8E1-11E9-9BD3-79D1E5697425 last_name: Elkrewi orcid: 0000-0002-5328-7231 citation: ama: Bett VK, Macon A, Vicoso B, Elkrewi MN. Chromosome-level assembly of Artemia franciscana sheds light on sex chromosome differentiation. Genome Biology and Evolution. 2024;16(1). doi:10.1093/gbe/evae006 apa: Bett, V. K., Macon, A., Vicoso, B., & Elkrewi, M. N. (2024). Chromosome-level assembly of Artemia franciscana sheds light on sex chromosome differentiation. Genome Biology and Evolution. Oxford University Press. https://doi.org/10.1093/gbe/evae006 chicago: Bett, Vincent K, Ariana Macon, Beatriz Vicoso, and Marwan N Elkrewi. “Chromosome-Level Assembly of Artemia Franciscana Sheds Light on Sex Chromosome Differentiation.” Genome Biology and Evolution. Oxford University Press, 2024. https://doi.org/10.1093/gbe/evae006. ieee: V. K. Bett, A. Macon, B. Vicoso, and M. N. Elkrewi, “Chromosome-level assembly of Artemia franciscana sheds light on sex chromosome differentiation,” Genome Biology and Evolution, vol. 16, no. 1. Oxford University Press, 2024. ista: Bett VK, Macon A, Vicoso B, Elkrewi MN. 2024. Chromosome-level assembly of Artemia franciscana sheds light on sex chromosome differentiation. Genome Biology and Evolution. 16(1), evae006. mla: Bett, Vincent K., et al. “Chromosome-Level Assembly of Artemia Franciscana Sheds Light on Sex Chromosome Differentiation.” Genome Biology and Evolution, vol. 16, no. 1, evae006, Oxford University Press, 2024, doi:10.1093/gbe/evae006. short: V.K. Bett, A. Macon, B. Vicoso, M.N. Elkrewi, Genome Biology and Evolution 16 (2024). corr_author: '1' date_created: 2024-02-18T23:01:02Z date_published: 2024-01-20T00:00:00Z date_updated: 2026-08-29T22:30:46Z day: '20' ddc: - '570' department: - _id: BeVi doi: 10.1093/gbe/evae006 external_id: isi: - '001153952800001' pmid: - '38245839' file: - access_level: open_access checksum: 106a40f10443b2e7ba66749844ebbdf1 content_type: application/pdf creator: dernst date_created: 2024-02-26T09:54:59Z date_updated: 2024-02-26T09:54:59Z file_id: '15029' file_name: 2024_GBE_Bett.pdf file_size: 5213306 relation: main_file success: 1 file_date_updated: 2024-02-26T09:54:59Z has_accepted_license: '1' intvolume: ' 16' isi: 1 issue: '1' language: - iso: eng month: '01' oa: 1 oa_version: Published Version pmid: 1 publication: Genome Biology and Evolution publication_identifier: eissn: - 1759-6653 publication_status: published publisher: Oxford University Press quality_controlled: '1' related_material: record: - id: '14705' relation: research_data status: public - id: '19386' relation: dissertation_contains status: public - id: '20449' relation: dissertation_contains status: public - id: '20444' relation: dissertation_contains status: deleted scopus_import: '1' status: public title: Chromosome-level assembly of Artemia franciscana sheds light on sex chromosome differentiation tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 16 year: '2024' ... --- OA_place: publisher _id: '17206' abstract: - lang: eng text: "Males and females exhibit numerous differences, from the initial stages of sex determination to the\r\ndevelopment of secondary sexual characteristics. In Drosophila, these differences have been\r\nthoroughly studied. Extensive research has been performed to understand the role and molecular\r\nmode of action of central sex in determining switch genes, such as transformer (tra) and Sex-lethal\r\n(Sxl). Furthermore, studies have highlighted differential gene expression as an essential mechanism to\r\ncreate sexual dimorphism. An alternative path to sexual dimorphism that has been less explored is\r\nalternative splicing, the mechanism through which genes can produce multiple transcripts with\r\ndistinct properties and functions. The primary switch sex-determining gene Sxl is a good example of\r\nthe role of alternative splicing for sex-specific functions: the inclusion of a specific exon determines\r\nthe male or female form of the protein, which in turn switches on either the male or female\r\ndevelopmental pathway. The genes that act upstream of Sxl and determine which form is expressed -\r\nthe counter genes - have received less attention. This thesis addresses two critical questions about\r\nthe molecular encoding of sexes in the Drosophila melanogaster genome: First, the use of splice forms\r\nin male and female tissues in D. melanogaster is examined, inferring the molecular and evolutionary\r\nparameters shaping the diversity of the splicing landscape. Second, the behaviour of counter genes in\r\nDrosophila-related species is investigated, shedding light on potential changes leading to their\r\nincorporation into the sex-determination pathway.\r\nFor the alternative splicing analyses, long-read RNA sequencing of testes, ovaries, female and male\r\nmidguts, heads, and whole bodies was performed. A novel pipeline was developed to assign unique\r\ntranscript identifiers for each sequence of exons and introns in the read, enabling detailed\r\ncomparisons of splicing variants in each tissue/sex. Alternative splicing was found to be more\r\npervasive in females than males (22,201 exclusive splice forms in females versus 12,631 in males),\r\nespecially when comparing ovaries to other tissues. The ovaries alone displayed 15,299 exclusive\r\nsplice forms, suggesting most female exclusive splice forms originate there. Genome location and gene\r\nage were also correlated with the number of splice forms per gene. In particular, the X and 4th\r\nchromosomes (Muller elements A and F) showed more splice forms per gene than other\r\nchromosomes. Additionally, genes older than 63 million years exhibited more splice forms per gene\r\nthan younger genes. Our results suggest that alternative splicing is more prevalent than previously\r\nbelieved, with numerous female-exclusive forms, age, and location playing significant roles in shaping\r\nits prevalence.\r\nFor the counter genes analyses, we combined published gene expression, genomic, and gene\r\ninteraction data from various clades (Bactrocera jarvisi, B. oleae, Ceratitis capitata, Mus musculus,\r\nCaenorhabditis elegans, Homo sapiens, and D. melanogaster). The counter genes scute (sc), extra\r\nmacrochaetae (emc), groucho (gro), deadpan (dpn), daughterless (da), runt (run), Sxl, hermaphrodite\r\n(her), and tra maintain conserved Muller element locations between C. capitata and D. melanogaster,\r\nwhich are most of the counter genes identified in the C. capitata genome. Their expression patterns\r\nduring early embryogenesis in B. jarvisi and D. melanogaster are also similar for counter genes dpn,\r\ngro, da, and emc. However, Sxl and sc are also found to have more extreme expression ratios between\r\nthe species. Lastly, gene interactions within the counter genes are conserved, with da-sc and gro-dpn\r\ninteractions occurring in Drosophila, worms, humans, and mice. Interactions such as dpn-sc, dpn-da,\r\nda-emc, and gro-run are present in Drosophila, mice, and humans, suggesting these genes were\r\nrecruited by ancestral characteristics, primarily during embryogenesis. The conserved expression,\r\nlocation, and interactions of counter genes suggest serendipitous recruitment of such genes instead\r\nof a change in those characteristics as they were recruited for this function. " acknowledged_ssus: - _id: ScienComp alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Julia full_name: Raices, Julia id: 3EE67F22-F248-11E8-B48F-1D18A9856A87 last_name: Raices citation: ama: 'Raices J. Novel approaches to studying alternative splicing in Drosophila Melanogaster : Insights into sex-specific gene expression and the evolution of sex determination. 2024. doi:10.15479/at:ista:17206' apa: 'Raices, J. (2024). Novel approaches to studying alternative splicing in Drosophila Melanogaster : Insights into sex-specific gene expression and the evolution of sex determination. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:17206' chicago: 'Raices, Julia. “Novel Approaches to Studying Alternative Splicing in Drosophila Melanogaster : Insights into Sex-Specific Gene Expression and the Evolution of Sex Determination.” Institute of Science and Technology Austria, 2024. https://doi.org/10.15479/at:ista:17206.' ieee: 'J. Raices, “Novel approaches to studying alternative splicing in Drosophila Melanogaster : Insights into sex-specific gene expression and the evolution of sex determination,” Institute of Science and Technology Austria, 2024.' ista: 'Raices J. 2024. Novel approaches to studying alternative splicing in Drosophila Melanogaster : Insights into sex-specific gene expression and the evolution of sex determination. Institute of Science and Technology Austria.' mla: 'Raices, Julia. Novel Approaches to Studying Alternative Splicing in Drosophila Melanogaster : Insights into Sex-Specific Gene Expression and the Evolution of Sex Determination. Institute of Science and Technology Austria, 2024, doi:10.15479/at:ista:17206.' short: 'J. Raices, Novel Approaches to Studying Alternative Splicing in Drosophila Melanogaster : Insights into Sex-Specific Gene Expression and the Evolution of Sex Determination, Institute of Science and Technology Austria, 2024.' corr_author: '1' date_created: 2024-07-05T14:15:29Z date_published: 2024-07-05T00:00:00Z date_updated: 2026-04-07T13:03:22Z day: '05' ddc: - '570' degree_awarded: PhD department: - _id: BeVi - _id: GradSch doi: 10.15479/at:ista:17206 ec_funded: 1 file: - access_level: closed checksum: d5e9234bde8667b005a8cfe18bb467d3 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: cchlebak date_created: 2024-07-11T07:18:01Z date_updated: 2025-01-11T23:30:04Z embargo_to: open_access file_id: '17223' file_name: ThesisRaices2024_postDefense.docx file_size: 13788479 relation: source_file - access_level: open_access checksum: f5ed0139aa3e11ce58369f0915647c5c content_type: application/pdf creator: cchlebak date_created: 2024-07-11T07:22:32Z date_updated: 2025-01-11T23:30:04Z embargo: 2025-01-11 file_id: '17224' file_name: ThesisRaices2024_nosignature.pdf file_size: 5580296 relation: main_file file_date_updated: 2025-01-11T23:30:04Z has_accepted_license: '1' language: - iso: eng month: '07' oa: 1 oa_version: Published Version page: '82' project: - _id: 250BDE62-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '715257' name: Prevalence and Influence of Sexual Antagonism on Genome Evolution publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria status: public supervisor: - first_name: Beatriz full_name: Vicoso, Beatriz id: 49E1C5C6-F248-11E8-B48F-1D18A9856A87 last_name: Vicoso orcid: 0000-0002-4579-8306 title: 'Novel approaches to studying alternative splicing in Drosophila Melanogaster : Insights into sex-specific gene expression and the evolution of sex determination' tmp: image: /images/cc_by_sa.png legal_code_url: https://creativecommons.org/licenses/by-sa/4.0/legalcode name: Creative Commons Attribution-ShareAlike 4.0 International Public License (CC BY-SA 4.0) short: CC BY-SA (4.0) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2024' ... --- OA_place: publisher _id: '18101' abstract: - lang: eng text: "The Retroviridae family consists of two sub-families, the Orthoretrovirinae and the\r\nSpumaretrovirinae. The Orthoretroviruses contain important human pathogens, such as the\r\nhuman immunodeficiency virus 1 (HIV-1). They also harbor other retrovirus species which\r\nare regularly used as model systems to study the retroviral life cycle. The main structural\r\ncomponent of the retroviruses, is the Gag protein and its truncation derivatives occurring\r\nduring viral maturation. Orthoretroviral Gag assemblies have been extensively studied to\r\nunderstand the interactions that confer stability and morphology to viral particles.\r\nThe Spumaretrovirinae subfamily represent an early diverging branch of the Retroviridae.\r\nIts members, the Foamy viruses (FV), share most of the conventional features found in\r\nretroviruses. However, they also possess multiple characteristics that make them unique. In\r\nparticular, FV Gag does not get extensively cleaved as in orthoretroviruses. Hence, the Gag\r\narchitecture deviates from the canonical domain arrangement in FV. They also exhibit a\r\npeculiar particle morphology, having no apparent immature state and a seemingly\r\nicosahedral mature particle. Due to this, many fundamental questions on FV structural\r\nassembly mechanisms remain open. To answer these questions, was the main focus of this\r\nthesis.\r\nMainly, it is not known how FV assemble their core in a virus particle and what are the\r\nimportant assembly interaction sites within said core. What is the minimum assembly\r\ncompetent domain of FV Gag? Is there a morphological change in the assembly type of FVGag lattices? If so, what is defining these morphological shifts? Finally, it would be\r\ninteresting to know what is the evolutionary relationship between FV and the rest of the\r\nretrotranscribing elements, from a structural point of view?\r\nTo answer these questions, membrane-enveloped mammalian cell-derived FV virus-like\r\nparticles (VLPs) were produced. Cryo-electron tomography (cryo-ET) analysis suggested\r\nthese FV VLPs do not form a canonical retroviral Gag lattice structure, which is in line with\r\nearlier observations. To further evaluate FV Gag assembly competence and morphology,\r\nthe first bacterial cell-derived in vitro VLP assembly system was designed and optimized.\r\nUsing this system with different truncation variants, the minimum assembly competent\r\ndomain of FV Gag was found to be the putative CA300-477 domain. Varying VLP\r\nmorphologies were also observed and strongly suggested residues upstream of CA300-477\r\nplay a role in morphology determination. Finally, a combined cryo-electron microscopy (cryoEM) and cryo-ET approach was taken to analyze tubular assemblies from the minimal\r\nassembly competent domain. This revealed an unexpectedly unique non-canonical\r\nassembly architecture. Three novel lattice stabilizing interfaces were described which\r\nproved to be as unique as the lattice arrangement. Comparison to a newly published FV CA\r\ncore structure revealed the CA-CA interactions in the atypical assembly do not recapitulate\r\nwhat is described for the FV core lattice. However, the new in vitro VLP assembly system\r\nobtained in this thesis also provides an exciting opportunity to study still unresolved FV\r\nassembly features in a potentially facilitated approach compared to conventional methods.\r\nIn summary, this work provided a deeper understanding of the basic FV Gag assembly unit,\r\nas well as presenting the first FV Gag-derived in vitro VLP assembly system. This system\r\nreveals a novel and unique assembly architecture among retroviral in vitro assemblies." acknowledged_ssus: - _id: EM-Fac - _id: LifeSc - _id: ScienComp alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Dario J full_name: Porley, Dario J id: 2FD6EA6C-F248-11E8-B48F-1D18A9856A87 last_name: Porley citation: ama: Porley Esteves D. Structural characterization of spumavirus capsid assemblies. 2024. doi:10.15479/at:ista:18101 apa: Porley Esteves, D. (2024). Structural characterization of spumavirus capsid assemblies. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:18101 chicago: Porley Esteves, Darío. “Structural Characterization of Spumavirus Capsid Assemblies.” Institute of Science and Technology Austria, 2024. https://doi.org/10.15479/at:ista:18101. ieee: D. Porley Esteves, “Structural characterization of spumavirus capsid assemblies,” Institute of Science and Technology Austria, 2024. ista: Porley Esteves D. 2024. Structural characterization of spumavirus capsid assemblies. Institute of Science and Technology Austria. mla: Porley Esteves, Darío. Structural Characterization of Spumavirus Capsid Assemblies. Institute of Science and Technology Austria, 2024, doi:10.15479/at:ista:18101. short: D. Porley Esteves, Structural Characterization of Spumavirus Capsid Assemblies, Institute of Science and Technology Austria, 2024. corr_author: '1' date_created: 2024-09-20T10:21:03Z date_published: 2024-09-26T00:00:00Z date_updated: 2026-04-07T13:21:01Z day: '26' ddc: - '570' degree_awarded: PhD department: - _id: GradSch - _id: FlSc doi: 10.15479/at:ista:18101 ec_funded: 1 file: - access_level: closed checksum: 3b8b0bacfe61112f3852744f3170e468 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: dporley date_created: 2024-09-26T13:40:33Z date_updated: 2025-03-25T23:30:03Z embargo_to: open_access file_id: '18149' file_name: PhD_thesis_DPorley_final_20240919.docx file_size: 14213128 relation: source_file - access_level: open_access checksum: 6c3a652a8eede874118e11d66a63652f content_type: application/pdf creator: dporley date_created: 2024-09-26T13:41:39Z date_updated: 2025-03-25T23:30:03Z embargo: 2025-03-25 file_id: '18150' file_name: PhD_thesis_DPorley_final_20240926_pdfa1.pdf file_size: 18583031 relation: main_file file_date_updated: 2025-03-25T23:30:03Z has_accepted_license: '1' language: - iso: eng month: '09' oa: 1 oa_version: Published Version page: '131' project: - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program - _id: 9B9C98E0-BA93-11EA-9121-9846C619BF3A grant_number: '25762' name: Structural characterization of spumavirus capsid assemblies to understand conserved Ortervirales assembly mechanisms publication_identifier: isbn: - 978-3-99078-041-1 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria status: public supervisor: - first_name: Florian KM full_name: Schur, Florian KM id: 48AD8942-F248-11E8-B48F-1D18A9856A87 last_name: Schur orcid: 0000-0003-4790-8078 title: Structural characterization of spumavirus capsid assemblies type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2024' ... --- OA_place: publisher _id: '17319' abstract: - lang: eng text: "This thesis comprises two distinct projects, each offering unique insights into fundamental\r\ncellular processes. While distinct in their focus, these different perspectives have a common\r\ntheme: chemiosmotic theory and utilisation of the proton gradient for driving the essential\r\nprocesses like auxin efflux and ATP synthesis, effectively bridging the membrane protein\r\nstructure and function from the realms of plant biology and cellular bioenergetics.\r\nThe first project of this thesis centres on the characterisation of PIN proteins, a class of\r\ntransmembrane transporters pivotal in the regulation of auxin transport and distribution in\r\nplants. PINs form a conserved and phylogenetically abundant group of transporters present in\r\nland plants and certain algae. Despite their great importance, they were one of the few elusive\r\nproteins essential for plant development not to be structurally and mechanistically\r\ncharacterised since their discovery almost 30 years ago. This work aimed to uncover the\r\nstructural and functional dynamics of the PIN protein-mediated auxin transport using an array\r\nof experimental techniques, including protein purification, biochemical assays and structural\r\nanalysis. Through an exhaustive screening process that took several years and included testing\r\ndifferent PIN homologues, expression systems, constructs, and purification conditions, we\r\ndeveloped a robust protocol for isolating the pure, stable, and monodisperse PIN8 protein.\r\nMoreover, utilising biophysical methods and buffer screening, we demonstrated that PIN8\r\nexhibits detergent and pH-dependent stability, with mild detergents and lower pH (5.0 and 6.0)\r\nbeing optimal for the stability of the protein. Using SEC-MALS and crosslinking, we\r\ndetermined that PIN8 forms dimers, which was confirmed by our structural studies. We\r\nobtained a cryo-EM map of PIN8 at pH 6.0, and, compared to recently published structures,\r\nour map implies major pH-dependent conformational changes and possibly utilisation of the\r\nproton gradient in the transport mechanism.\r\nThe subject of the second project was F1Fo-ATP synthase, an enzyme complex fundamental\r\nto cellular energy metabolism. Through an approach integrating biochemical assays and\r\nstructural analysis, this research aimed to unveil the molecular mechanism of inhibition of ATP\r\nsynthase by yaku´amide, a bioactive compound with potential therapeutic implications. Using\r\nsubmitochondrial particles and purified F1Fo-ATP synthase, we demonstrated that, contrary to\r\npublished data, yaku´amide inhibits both ATP hydrolysis and ATP synthesis reactions.\r\nMoreover, we found that yaku´amide inhibitory activity is proton motive force (pmf)\r\ndependent, with lower inhibition in a more coupled system. Utilising cryo-EM, we obtained\r\nmaps and models for the three main rotational states of murine ATP synthase (State 1 at 3.0 Å,\r\n8\r\nState 2 at 3.1 Å, and State 3 at 3.2 Å, overall). We observed several new features in our maps;\r\nhowever, we cannot definitively determine the exact mechanism of yaku amide’s inhibition on\r\nthe protein due to either resolution limits or suboptimal binding of the inhibitor." acknowledged_ssus: - _id: EM-Fac - _id: LifeSc alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Kristina full_name: Lukic, Kristina id: 2B04DB84-F248-11E8-B48F-1D18A9856A87 last_name: Lukic orcid: 0000-0003-1581-881X citation: ama: 'Lukic K. Membrane proteins in plant physiology and bioenergetics : Investigating auxin efflux transporter PIN8 and ATP synthase inhibition by the novel inhibitor Yaku’amide B. 2024. doi:10.15479/at:ista:17319' apa: 'Lukic, K. (2024). Membrane proteins in plant physiology and bioenergetics : Investigating auxin efflux transporter PIN8 and ATP synthase inhibition by the novel inhibitor Yaku’amide B. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:17319' chicago: 'Lukic, Kristina. “Membrane Proteins in Plant Physiology and Bioenergetics : Investigating Auxin Efflux Transporter PIN8 and ATP Synthase Inhibition by the Novel Inhibitor Yaku’amide B.” Institute of Science and Technology Austria, 2024. https://doi.org/10.15479/at:ista:17319.' ieee: 'K. Lukic, “Membrane proteins in plant physiology and bioenergetics : Investigating auxin efflux transporter PIN8 and ATP synthase inhibition by the novel inhibitor Yaku’amide B,” Institute of Science and Technology Austria, 2024.' ista: 'Lukic K. 2024. Membrane proteins in plant physiology and bioenergetics : Investigating auxin efflux transporter PIN8 and ATP synthase inhibition by the novel inhibitor Yaku’amide B. Institute of Science and Technology Austria.' mla: 'Lukic, Kristina. Membrane Proteins in Plant Physiology and Bioenergetics : Investigating Auxin Efflux Transporter PIN8 and ATP Synthase Inhibition by the Novel Inhibitor Yaku’amide B. Institute of Science and Technology Austria, 2024, doi:10.15479/at:ista:17319.' short: 'K. Lukic, Membrane Proteins in Plant Physiology and Bioenergetics : Investigating Auxin Efflux Transporter PIN8 and ATP Synthase Inhibition by the Novel Inhibitor Yaku’amide B, Institute of Science and Technology Austria, 2024.' corr_author: '1' date_created: 2024-07-26T09:05:55Z date_published: 2024-07-26T00:00:00Z date_updated: 2026-04-07T13:20:44Z day: '26' ddc: - '580' degree_awarded: PhD department: - _id: LeSa - _id: GradSch doi: 10.15479/at:ista:17319 file: - access_level: open_access checksum: 95517e697ea6a87e267e649cad560989 content_type: application/pdf creator: cchlebak date_created: 2024-07-26T13:14:24Z date_updated: 2025-01-26T23:30:04Z embargo: 2025-01-26 file_id: '17320' file_name: Thesis_Kristina_Lukic.pdf file_size: 24639084 relation: main_file - access_level: closed checksum: 74325746a9a05078fb9935dbf2aef752 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: cchlebak date_created: 2024-07-26T13:14:50Z date_updated: 2025-01-26T23:30:04Z embargo_to: open_access file_id: '17321' file_name: Thesis_Kristina_Lukic.docx file_size: 96334272 relation: source_file file_date_updated: 2025-01-26T23:30:04Z has_accepted_license: '1' language: - iso: eng month: '07' oa: 1 oa_version: Published Version page: '224' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria status: public supervisor: - first_name: Leonid A full_name: Sazanov, Leonid A id: 338D39FE-F248-11E8-B48F-1D18A9856A87 last_name: Sazanov orcid: 0000-0002-0977-7989 title: 'Membrane proteins in plant physiology and bioenergetics : Investigating auxin efflux transporter PIN8 and ATP synthase inhibition by the novel inhibitor Yaku''amide B' type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2024' ... --- OA_place: publisher _id: '17346' abstract: - lang: eng text: "Acquiring, retaining, and retrieving information over a wide range of timescales are crucial\r\nfunctions of the brain. The successful processing of memories affects many aspects of our\r\nlives and enables us and many other organisms to operate in a complex environment and\r\nto interact with it. In this context, the hippocampus and functionally connected brain\r\nareas, such as the prefrontal cortex, are central and have been subject to intensive research\r\nin the past decades. Storage of memories is believed to rely on distributed neural activity\r\nwithin these neural circuits. Additionally, neural memory traces of recent experience are\r\nreinstated during periods of rest or sleep. These reactivations are thought to play an\r\noutstanding role in the consolidation of memories and potentially facilitate the transfer of\r\ninformation from the hippocampus to cortical areas for long-term storage and integration\r\ninto existing knowledge.\r\nHowever, there is growing evidence that memory-related neural representations in the\r\nhippocampus are not as stable as initially thought and that they change even in the\r\nabsence of learning. It has been suggested that these changes reflect the accumulation of\r\nexperience, but the influence of interspersed consolidation periods has not been considered.\r\nPrevious studies have analyzed consolidation periods by detecting activity that strongly\r\nresembled neural activity during the acquisition of memory. Besides being often limited\r\nto only non-rapid eye movement (NREM) sleep, the used approaches were not capable of\r\ntracking changes in neural representations over extended temporal periods. More fluid\r\nrepresentations do not only challenge our understanding of how information is stored, but\r\nthey also affect the transfer of information between brain areas during the consolidation\r\nprocess.\r\nFor this thesis, I investigated the evolution of memory-related activity during sleep\r\nperiods expected to be involved in consolidation in the hippocampus and between the\r\nhippocampus and prefrontal cortex. I found that reactivated activity in the hippocampus\r\ngradually transformed during prolonged periods of sleep and inactivity. In the beginning,\r\nneural activity strongly resembled acquisition activity, whereas, with the progression of\r\ntime, it became more similar to the subsequent recall activity. NREM periods drove\r\nthis process, while rapid-eye movement (REM) periods showed a resetting effect. This\r\nreactivation drift was due to firing rate changes of a subset of cells and mirrored the\r\nrepresentational changes from the acquisition to the recall. A stable subset of cells\r\nwithstood the drift and maintained their activity. Therefore, my results indicate that\r\nmemory-related representations undergo spontaneous modifications during consolidation\r\nperiods and that these changes are predictive of representational drift.\r\nFurthermore, I found that the amount of change in the neural activity during subsequent\r\nsleep periods was biased by prior behavioral performance. Observed changes in the\r\nhippocampus and the prefrontal cortex were synchronized and increased after poor\r\nperformance, highlighting a potential role in the exchange of information. Low-variance\r\nvii\r\nperiods with distinct, more stable activity from a subset of cells significantly contributed\r\nto the heightened synchrony between both areas. Hence, interleaved phases of more stable\r\nneural activity could facilitate the information transfer between brain areas.\r\nIn conclusion, my investigations underline the fluidity of memory-related representations\r\nand assign a prominent role to sleep reactivation periods in their evolution. In addition, I\r\nidentified a potential mechanism of stable activity phases that might facilitate the synchronization across hippocampal-prefrontal activity despite ongoing changes. Reconciling\r\nand integrating findings from both spontaneous and behaviorally-related representational\r\nchanges in functionally related brain areas will help to broaden our understanding of how\r\nknowledge is stored, maintained, updated, and transferred between brain areas." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Lars full_name: Bollmann, Lars id: 47AD3038-F248-11E8-B48F-1D18A9856A87 last_name: Bollmann citation: ama: Bollmann L. Stability and change in the memory system during rest. 2024. doi:10.15479/at:ista:17346 apa: Bollmann, L. (2024). Stability and change in the memory system during rest. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:17346 chicago: Bollmann, Lars. “Stability and Change in the Memory System during Rest.” Institute of Science and Technology Austria, 2024. https://doi.org/10.15479/at:ista:17346. ieee: L. Bollmann, “Stability and change in the memory system during rest,” Institute of Science and Technology Austria, 2024. ista: Bollmann L. 2024. Stability and change in the memory system during rest. Institute of Science and Technology Austria. mla: Bollmann, Lars. Stability and Change in the Memory System during Rest. Institute of Science and Technology Austria, 2024, doi:10.15479/at:ista:17346. short: L. Bollmann, Stability and Change in the Memory System during Rest, Institute of Science and Technology Austria, 2024. corr_author: '1' date_created: 2024-07-29T15:08:42Z date_published: 2024-07-31T00:00:00Z date_updated: 2026-04-07T13:21:20Z day: '31' ddc: - '573' degree_awarded: PhD department: - _id: GradSch - _id: JoCs doi: 10.15479/at:ista:17346 file: - access_level: open_access checksum: 12c76297cc27449da80c60d79127770d content_type: application/pdf creator: lbollman date_created: 2024-07-31T18:37:19Z date_updated: 2025-01-31T23:30:03Z embargo: 2025-01-31 file_id: '17359' file_name: PhD_Thesis_Lars_Bollmann.pdf file_size: 12920169 relation: main_file - access_level: closed checksum: 19a0265079dec8038830ad6e35c5106e content_type: application/zip creator: lbollman date_created: 2024-07-31T18:38:39Z date_updated: 2025-01-31T23:30:03Z embargo_to: open_access file_id: '17360' file_name: Latex_source.zip file_size: 27568807 relation: source_file file_date_updated: 2025-01-31T23:30:03Z has_accepted_license: '1' keyword: - Memory - Hippocampus - Consolidation language: - iso: eng month: '07' oa: 1 oa_version: Published Version page: '103' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria status: public supervisor: - first_name: Jozsef L full_name: Csicsvari, Jozsef L id: 3FA14672-F248-11E8-B48F-1D18A9856A87 last_name: Csicsvari orcid: 0000-0002-5193-4036 title: Stability and change in the memory system during rest type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2024' ... --- OA_place: publisher _id: '18129' abstract: - lang: eng text: "State-of-the-art quantum computers, with roughly a thousand qubits, face a crucial technological challenge of scaling up. Spins confined in quantum dots (QDs) are a promising candidate\r\nfor qubits due to their long coherence, tunability, control, and readout. However, their natural\r\ncoupling is the short-ranged (∼ 100 nm) exchange interaction, limited to nearest neighbours.\r\nLong-ranged (∼ 1 mm) qubit interactions mediated by a photon could be engineered through a\r\ncoherent spin-photon coupling. Achieving a strong coupling to a photon is inherently challenging in QDs due to the small dipole moment of the confined charge. However, the potential of\r\nhigh-impedance resonators to compensate for this has gained significant attention in the past\r\ndecade. Nevertheless, previous QD circuit quantum electrodynamics implementations have not\r\nexceeded the impedance of ∼ 3.8 kΩ, leaving opportunities for significant improvement. The\r\nlarge kinetic inductance of granular aluminium (grAl) could provide an order-of-magnitude\r\nenhancement. However, fully exploiting the potential of disordered or granular superconductors\r\nis challenging as their impedances close to the superconductor-to-insulator transition are\r\ndifficult to control reproducibly. We report on the realization of a wireless ohmmeter which\r\nallows in situ resistance measurements during film deposition and, therefore, indirect control\r\nof the kinetic inductance of grAl films. This allows us to reproducibly fabricate resonators\r\nwith characteristic impedance exceeding the resistance quantum, even reaching 22.3 kW, due\r\nto the large sheet kinetic inductance of up to 3 nH □−1\r\n. By integrating an 8 kW resonator\r\nwith a germanium double QD, we demonstrate a strong charge-photon coupling with the\r\nhighest rate reported, 566 MHz. The demonstrated method and grAl properties make these\r\nresonators suitable for boosting the spin-photon coupling strength, a crucial requirement for\r\nfast, high-fidelity, long-distance two-qubit gates.\r\n" acknowledged_ssus: - _id: M-Shop - _id: NanoFab alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Marian full_name: Janik, Marian id: 396A1950-F248-11E8-B48F-1D18A9856A87 last_name: Janik orcid: 0009-0003-9037-8831 citation: ama: Janik M. Strong charge-photon coupling in Germanium enabled by granular aluminium superinductors. 2024. doi:10.15479/at:ista:18129 apa: Janik, M. (2024). Strong charge-photon coupling in Germanium enabled by granular aluminium superinductors. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:18129 chicago: Janik, Marian. “Strong Charge-Photon Coupling in Germanium Enabled by Granular Aluminium Superinductors.” Institute of Science and Technology Austria, 2024. https://doi.org/10.15479/at:ista:18129. ieee: M. Janik, “Strong charge-photon coupling in Germanium enabled by granular aluminium superinductors,” Institute of Science and Technology Austria, 2024. ista: Janik M. 2024. Strong charge-photon coupling in Germanium enabled by granular aluminium superinductors. Institute of Science and Technology Austria. mla: Janik, Marian. Strong Charge-Photon Coupling in Germanium Enabled by Granular Aluminium Superinductors. Institute of Science and Technology Austria, 2024, doi:10.15479/at:ista:18129. short: M. Janik, Strong Charge-Photon Coupling in Germanium Enabled by Granular Aluminium Superinductors, Institute of Science and Technology Austria, 2024. corr_author: '1' date_created: 2024-09-23T17:25:43Z date_published: 2024-09-24T00:00:00Z date_updated: 2026-06-03T07:16:03Z day: '24' ddc: - '539' degree_awarded: PhD department: - _id: GradSch - _id: GeKa doi: 10.15479/at:ista:18129 file: - access_level: closed checksum: dc15958f6400b5bdaa28bf58fc7a4056 content_type: application/x-zip-compressed creator: mjanik date_created: 2024-09-23T17:15:09Z date_updated: 2025-05-23T22:30:09Z embargo_to: open_access file_id: '18130' file_name: janik_thesis.zip file_size: 156207943 relation: source_file - access_level: open_access checksum: 74737aee285dc1f491643327350efe9c content_type: application/pdf creator: mjanik date_created: 2024-09-23T17:15:30Z date_updated: 2025-05-23T22:30:09Z embargo: 2025-05-23 file_id: '18131' file_name: janik_thesis_pdfa.pdf file_size: 96195684 relation: main_file file_date_updated: 2025-05-23T22:30:09Z has_accepted_license: '1' language: - iso: eng month: '09' oa: 1 oa_version: Published Version page: '164' project: - _id: c0977eea-5a5b-11eb-8a69-a862db0cf4d1 grant_number: I05060 name: High impedance circuit quantum electrodynamics with hole spins - _id: bd8bd29e-d553-11ed-ba76-f0070d4b237a grant_number: P36507 name: Merging spin and superconducting qubits in planar Ge - _id: 237B3DA4-32DE-11EA-91FC-C7463DDC885E call_identifier: FWF grant_number: P32235 name: Towards scalable hut wire quantum devices - _id: 34c0acea-11ca-11ed-8bc3-8775e10fd452 grant_number: '101069515' name: Integrated Germanium Quantum Technology - _id: eb9b30ac-77a9-11ec-83b8-871f581d53d2 name: Protected states of quantum matter publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '18144' relation: part_of_dissertation status: public status: public supervisor: - first_name: Georgios full_name: Katsaros, Georgios id: 38DB5788-F248-11E8-B48F-1D18A9856A87 last_name: Katsaros orcid: 0000-0001-8342-202X title: Strong charge-photon coupling in Germanium enabled by granular aluminium superinductors tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2024' ... --- OA_place: publisher _id: '17368' abstract: - lang: eng text: "Recent advancements in molecular diagnostic techniques have enabled the collection of\r\nmultiple types of omics data from patients, including genomics, epigenomics, proteomics,\r\nand transcriptomics. However, we lack effective methods for integrating all these different\r\ndata types and combining them with clinical outcomes to study the molecular mechanisms\r\nthat govern pathological phenotypes. We present multi-omics BayesW, a penalized Bayesian\r\nregression method that can handle general omics data for survival analysis of time-to-event\r\nphenotypes. Our method can: (1) accommodate incomplete data by allowing censored\r\nindividuals, (2) use continuous time-to-event data to test associations of markers with a\r\nphenotype and (3) estimate effects jointly while allowing for independent groups of biological\r\nmarkers. Extensive simulations using planted signals on real data demonstrate that our model\r\naccurately retrieves the true parameters of the model while controlling for false discoveries\r\nand maintaining the expected prediction accuracy. We address data correlations by estimating\r\nthe effects jointly, even between omic groups, while also estimating the individual variance\r\nexplained by each group. We apply our model to two datasets. Using 18,000 individuals from\r\nthe Generation Scotland study we model the association of time at onset of Type 2 Diabetes,\r\nStroke, Ischemic Disease, and Osteoarthritis from baseline study entry, with 831,724 CpG\r\nmethylation probes. We find that large proportions of variation in disease onset times can\r\nbe attributed to methylation as measured in whole blood at baseline in individuals without\r\ndisease symptoms. We then apply our model to The Cancer Genome Atlas (TCGA) pan-cancer\r\ndataset, in which we use 5 types of omics: copy number variation, epigenetics, somatic\r\nmutations, miRNA, and gene expression. For cancer survival age-at-onset we find that, when\r\nfitting the 5 groups together, almost all variation attributable to \"omics\" data is explained by\r\nDNA methylation. When considering progression times, both methylation and gene expression\r\nexplain a large part of the variance. We found 2 genes that are significantly associated (95%\r\nposterior inclusion probability) with cancer survival time, conditional on all other genome-wide\r\nomics data variation. Owing to the vast variability of mechanisms characterizing different\r\ncancers, there are likely few specific genes with a strong signal in a pan-cancer setting. Taken\r\ntogether, we showed the applicability of our multi-omics BayesW model to a wide-range of\r\nbiological questions in multi-omics data.\r\n" alternative_title: - ISTA Master's Thesis article_processing_charge: No author: - first_name: Ariadna full_name: Villanueva Marijuan, Ariadna id: e0ae4864-133f-11ed-8f02-adaa8dd27540 last_name: Villanueva Marijuan citation: ama: Villanueva Marijuan A. Bayesian linear regression for analyzing general omics data with time-to-event phenotypes. 2024. doi:10.15479/at:ista:17368 apa: Villanueva Marijuan, A. (2024). Bayesian linear regression for analyzing general omics data with time-to-event phenotypes. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:17368 chicago: Villanueva Marijuan, Ariadna. “Bayesian Linear Regression for Analyzing General Omics Data with Time-to-Event Phenotypes.” Institute of Science and Technology Austria, 2024. https://doi.org/10.15479/at:ista:17368. ieee: A. Villanueva Marijuan, “Bayesian linear regression for analyzing general omics data with time-to-event phenotypes,” Institute of Science and Technology Austria, 2024. ista: Villanueva Marijuan A. 2024. Bayesian linear regression for analyzing general omics data with time-to-event phenotypes. Institute of Science and Technology Austria. mla: Villanueva Marijuan, Ariadna. Bayesian Linear Regression for Analyzing General Omics Data with Time-to-Event Phenotypes. Institute of Science and Technology Austria, 2024, doi:10.15479/at:ista:17368. short: A. Villanueva Marijuan, Bayesian Linear Regression for Analyzing General Omics Data with Time-to-Event Phenotypes, Institute of Science and Technology Austria, 2024. corr_author: '1' date_created: 2024-08-02T10:52:40Z date_published: 2024-08-13T00:00:00Z date_updated: 2026-04-07T13:03:41Z day: '13' ddc: - '610' degree_awarded: MS department: - _id: GradSch - _id: MaRo doi: 10.15479/at:ista:17368 file: - access_level: open_access checksum: 0c2daa174609f0c00919dccc5701d375 content_type: application/pdf creator: avillanu date_created: 2024-08-14T11:51:24Z date_updated: 2025-02-14T23:30:03Z embargo: 2025-02-14 file_id: '17433' file_name: Masters_thesis_AriadnaVillanueva.pdf file_size: 13052436 relation: main_file - access_level: closed checksum: e9ed4465dfa539ac4c3a8d4d0b6271a1 content_type: application/zip creator: avillanu date_created: 2024-08-14T11:51:57Z date_updated: 2025-02-14T23:30:03Z embargo_to: open_access file_id: '17434' file_name: Masters thesis-AriadnaVillanueva.zip file_size: 45642547 relation: source_file file_date_updated: 2025-02-14T23:30:03Z has_accepted_license: '1' keyword: - Epigenetics - Multi-omics - Bayesian regression language: - iso: eng month: '08' oa: 1 oa_version: Published Version page: '60' publication_identifier: issn: - 2791-4585 publication_status: published publisher: Institute of Science and Technology Austria status: public supervisor: - first_name: Matthew Richard full_name: Robinson, Matthew Richard id: E5D42276-F5DA-11E9-8E24-6303E6697425 last_name: Robinson orcid: 0000-0001-8982-8813 title: Bayesian linear regression for analyzing general omics data with time-to-event phenotypes tmp: image: /images/cc_by_nc_sa.png legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) short: CC BY-NC-SA (4.0) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2024' ...