--- _id: '179' abstract: - lang: eng text: An asymptotic formula is established for the number of rational points of bounded anticanonical height which lie on a certain Zariski dense subset of the biprojective hypersurface x1y21+⋯+x4y24=0 in ℙ3×ℙ3. This confirms the modified Manin conjecture for this variety, in which the removal of a thin set of rational points is allowed. article_processing_charge: No article_type: original arxiv: 1 author: - first_name: Timothy D full_name: Browning, Timothy D id: 35827D50-F248-11E8-B48F-1D18A9856A87 last_name: Browning orcid: 0000-0002-8314-0177 - first_name: Roger full_name: Heath Brown, Roger last_name: Heath Brown citation: ama: Browning TD, Heath Brown R. Density of rational points on a quadric bundle in ℙ3×ℙ3. Duke Mathematical Journal. 2020;169(16):3099-3165. doi:10.1215/00127094-2020-0031 apa: Browning, T. D., & Heath Brown, R. (2020). Density of rational points on a quadric bundle in ℙ3×ℙ3. Duke Mathematical Journal. Duke University Press. https://doi.org/10.1215/00127094-2020-0031 chicago: Browning, Timothy D, and Roger Heath Brown. “Density of Rational Points on a Quadric Bundle in ℙ3×ℙ3.” Duke Mathematical Journal. Duke University Press, 2020. https://doi.org/10.1215/00127094-2020-0031. ieee: T. D. Browning and R. Heath Brown, “Density of rational points on a quadric bundle in ℙ3×ℙ3,” Duke Mathematical Journal, vol. 169, no. 16. Duke University Press, pp. 3099–3165, 2020. ista: Browning TD, Heath Brown R. 2020. Density of rational points on a quadric bundle in ℙ3×ℙ3. Duke Mathematical Journal. 169(16), 3099–3165. mla: Browning, Timothy D., and Roger Heath Brown. “Density of Rational Points on a Quadric Bundle in ℙ3×ℙ3.” Duke Mathematical Journal, vol. 169, no. 16, Duke University Press, 2020, pp. 3099–165, doi:10.1215/00127094-2020-0031. short: T.D. Browning, R. Heath Brown, Duke Mathematical Journal 169 (2020) 3099–3165. date_created: 2018-12-11T11:45:02Z date_published: 2020-09-10T00:00:00Z date_updated: 2024-10-21T06:02:33Z day: '10' department: - _id: TiBr doi: 10.1215/00127094-2020-0031 external_id: arxiv: - '1805.10715' isi: - '000582676300002' intvolume: ' 169' isi: 1 issue: '16' language: - iso: eng main_file_link: - open_access: '1' url: https://arxiv.org/abs/1805.10715 month: '09' oa: 1 oa_version: Preprint page: 3099-3165 publication: Duke Mathematical Journal publication_identifier: issn: - 0012-7094 publication_status: published publisher: Duke University Press quality_controlled: '1' scopus_import: '1' status: public title: Density of rational points on a quadric bundle in ℙ3×ℙ3 type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 169 year: '2020' ... --- OA_place: publisher _id: '8340' abstract: - lang: eng text: Mitochondria are sites of oxidative phosphorylation in eukaryotic cells. Oxidative phosphorylation operates by a chemiosmotic mechanism made possible by redox-driven proton pumping machines which establish a proton motive force across the inner mitochondrial membrane. This electrochemical proton gradient is used to drive ATP synthesis, which powers the majority of cellular processes such as protein synthesis, locomotion and signalling. In this thesis I investigate the structures and molecular mechanisms of two inner mitochondrial proton pumping enzymes, respiratory complex I and transhydrogenase. I present the first high-resolution structure of the full transhydrogenase from any species, and a significantly improved structure of complex I. Improving the resolution from 3.3 Å available previously to up to 2.3 Å in this thesis allowed us to model bound water molecules, crucial in the proton pumping mechanism. For both enzymes, up to five cryo-EM datasets with different substrates and inhibitors bound were solved to delineate the catalytic cycle and understand the proton pumping mechanism. In transhydrogenase, the proton channel is gated by reversible detachment of the NADP(H)-binding domain which opens the proton channel to the opposite sites of the membrane. In complex I, the proton channels are gated by reversible protonation of key glutamate and lysine residues and breaking of the water wire connecting the proton pumps with the quinone reduction site. The tight coupling between the redox and the proton pumping reactions in transhydrogenase is achieved by controlling the NADP(H) exchange which can only happen when the NADP(H)-binding domain interacts with the membrane domain. In complex I, coupling is achieved by cycling of the whole complex between the closed state, in which quinone can get reduced, and the open state, in which NADH can induce quinol ejection from the binding pocket. On the basis of these results I propose detailed mechanisms for catalytic cycles of transhydrogenase and complex I that are consistent with a large amount of previous work. In both enzymes, conformational and electrostatic mechanisms contribute to the overall catalytic process. Results presented here could be used for better understanding of the human pathologies arising from deficiencies of complex I or transhydrogenase and could be used to develop novel therapies. acknowledged_ssus: - _id: EM-Fac acknowledgement: 'I acknowledge the support of IST facilities, especially the Electron Miscroscopy facility for providing training and resources. Special thanks also go to cryo-EM specialists who helped me to collect the data present here: Dr Valentin Hodirnau (IST Austria), Dr Tom Heuser (IMBA, Vienna), Dr Rebecca Thompson (Uni. of Leeds) and Dr Jirka Nováček (CEITEC). This work has been supported by iNEXT, project number 653706, funded by the Horizon 2020 programme of the European Union. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 665385.' alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Domen full_name: Kampjut, Domen id: 37233050-F248-11E8-B48F-1D18A9856A87 last_name: Kampjut orcid: 0000-0002-6018-3422 citation: ama: Kampjut D. Molecular mechanisms of mitochondrial redox-coupled proton pumping enzymes. 2020. doi:10.15479/AT:ISTA:8340 apa: Kampjut, D. (2020). Molecular mechanisms of mitochondrial redox-coupled proton pumping enzymes. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8340 chicago: Kampjut, Domen. “Molecular Mechanisms of Mitochondrial Redox-Coupled Proton Pumping Enzymes.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8340. ieee: D. Kampjut, “Molecular mechanisms of mitochondrial redox-coupled proton pumping enzymes,” Institute of Science and Technology Austria, 2020. ista: Kampjut D. 2020. Molecular mechanisms of mitochondrial redox-coupled proton pumping enzymes. Institute of Science and Technology Austria. mla: Kampjut, Domen. Molecular Mechanisms of Mitochondrial Redox-Coupled Proton Pumping Enzymes. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8340. short: D. Kampjut, Molecular Mechanisms of Mitochondrial Redox-Coupled Proton Pumping Enzymes, Institute of Science and Technology Austria, 2020. corr_author: '1' date_created: 2020-09-07T18:42:23Z date_published: 2020-09-09T00:00:00Z date_updated: 2026-04-08T07:43:58Z day: '09' ddc: - '572' degree_awarded: PhD department: - _id: LeSa doi: 10.15479/AT:ISTA:8340 ec_funded: 1 file: - access_level: closed checksum: dd270baf82121eb4472ad19d77bf227c content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: dkampjut date_created: 2020-09-08T13:32:06Z date_updated: 2021-09-11T22:30:04Z embargo_to: open_access file_id: '8345' file_name: ThesisFull20200908.docx file_size: 166146359 relation: source_file - access_level: open_access checksum: 82fce6f95ffa47ecc4ebca67ea2cc38c content_type: application/pdf creator: dernst date_created: 2020-09-14T15:02:20Z date_updated: 2021-09-11T22:30:04Z embargo: 2021-09-10 file_id: '8393' file_name: 2020_Thesis_Kampjut.pdf file_size: 13873769 relation: main_file file_date_updated: 2021-09-11T22:30:04Z has_accepted_license: '1' language: - iso: eng month: '09' oa: 1 oa_version: None page: '242' project: - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program publication_identifier: isbn: - 978-3-99078-008-4 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '6848' relation: part_of_dissertation status: public status: public supervisor: - first_name: Leonid A full_name: Sazanov, Leonid A id: 338D39FE-F248-11E8-B48F-1D18A9856A87 last_name: Sazanov orcid: 0000-0002-0977-7989 title: Molecular mechanisms of mitochondrial redox-coupled proton pumping enzymes type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2020' ... --- _id: '8350' abstract: - lang: eng text: "Cytoplasm is a gel-like crowded environment composed of tens of thousands of macromolecules, organelles, cytoskeletal networks and cytosol. The structure of the cytoplasm is thought to be highly organized and heterogeneous due to the crowding of its constituents and their effective compartmentalization. In such an environment, the diffusive dynamics of the molecules is very restricted, an effect that is further amplified by clustering and anchoring of molecules. Despite the jammed nature of the cytoplasm at the microscopic scale, large-scale reorganization of cytoplasm is essential for important cellular functions, such as nuclear positioning and cell division. How such mesoscale reorganization of the cytoplasm is achieved, especially for very large cells such as oocytes or syncytial tissues that can span hundreds of micrometers in size, has only begun to be understood.\r\nIn this thesis, I focus on the recent advances in elucidating the molecular, cellular and biophysical principles underlying cytoplasmic organization across different scales, structures and species. First, I outline which of these principles have been identified by reductionist approaches, such as in vitro reconstitution assays, where boundary conditions and components can be modulated at ease. I then describe how the theoretical and experimental framework established in these reduced systems have been applied to their more complex in vivo counterparts, in particular oocytes and embryonic syncytial structures, and discuss how such complex biological systems can initiate symmetry breaking and establish patterning.\r\nSpecifically, I examine an example of large-scale reorganizations taking place in zebrafish embryos, where extensive cytoplasmic streaming leads to the segregation of cytoplasm from yolk granules along the animal-vegetal axis of the embryo. Using biophysical experimentation and theory, I investigate the forces underlying this process, to show that this process does not rely on cortical actin reorganization, as previously thought, but instead on a cell-cycle-dependent bulk actin polymerization wave traveling from the animal to the vegetal pole of the embryo. This wave functions in segregation by both pulling cytoplasm animally and pushing yolk granules vegetally. Cytoplasm pulling is mediated by bulk actin network flows exerting friction forces on the cytoplasm, while yolk granule pushing is achieved by a mechanism closely resembling actin comet formation on yolk granules. This study defines a novel role of bulk actin polymerization waves in embryo polarization via cytoplasmic segregation. Lastly, I describe the cytoplasmic reorganizations taking place during zebrafish oocyte maturation, where the initial segregation of the cytoplasm and yolk granules occurs. Here, I demonstrate a previously uncharacterized wave of microtubule aster formation, traveling the oocyte along the animal-vegetal axis. Further research is required to determine the role of such microtubule structures in cytoplasmic reorganizations therein.\r\nCollectively, these studies provide further evidence for the coupling between cell cytoskeleton and cell cycle machinery, which can underlie a core self-organizing mechanism for orchestrating large-scale reorganizations in a cell-cycle-tunable manner, where the modulations of the force-generating machinery and cytoplasmic mechanics can be harbored to fulfill cellular functions." acknowledged_ssus: - _id: PreCl - _id: Bio - _id: EM-Fac acknowledgement: "I would have had no fish and hence no results without our wonderful fish facility crew, Verena Mayer, Eva Schlegl, Andreas Mlak and Matthias Nowak. Special thanks to Verena for being always happy to help and dealing with our chaotic schedules in the lab. Danke auch, Verena, für deine Geduld, mit mir auf Deutsch zu sprechen. Das hat mir sehr geholfen.\r\nSpecial thanks to the Bioimaging and EM facilities at IST Austria for supporting us every day. Very special thanks would go to Robert Hauschild for his continuous support on data analysis and also to Jack Merrin for designing and building microfabricated chambers for the project and for the various discussions on making zebrafish extracts." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Shayan full_name: Shamipour, Shayan id: 40B34FE2-F248-11E8-B48F-1D18A9856A87 last_name: Shamipour citation: ama: Shamipour S. Bulk actin dynamics drive phase segregation in zebrafish oocytes . 2020. doi:10.15479/AT:ISTA:8350 apa: Shamipour, S. (2020). Bulk actin dynamics drive phase segregation in zebrafish oocytes . Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8350 chicago: Shamipour, Shayan. “Bulk Actin Dynamics Drive Phase Segregation in Zebrafish Oocytes .” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8350. ieee: S. Shamipour, “Bulk actin dynamics drive phase segregation in zebrafish oocytes ,” Institute of Science and Technology Austria, 2020. ista: Shamipour S. 2020. Bulk actin dynamics drive phase segregation in zebrafish oocytes . Institute of Science and Technology Austria. mla: Shamipour, Shayan. Bulk Actin Dynamics Drive Phase Segregation in Zebrafish Oocytes . Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8350. short: S. Shamipour, Bulk Actin Dynamics Drive Phase Segregation in Zebrafish Oocytes , Institute of Science and Technology Austria, 2020. corr_author: '1' date_created: 2020-09-09T11:12:10Z date_published: 2020-09-09T00:00:00Z date_updated: 2025-09-11T07:08:52Z day: '09' ddc: - '570' degree_awarded: PhD department: - _id: BjHo - _id: CaHe doi: 10.15479/AT:ISTA:8350 file: - access_level: closed checksum: 6e47871c74f85008b9876112eb3fcfa1 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: sshamip date_created: 2020-09-09T11:06:27Z date_updated: 2021-09-11T22:30:05Z embargo_to: open_access file_id: '8351' file_name: Shayan-Thesis-Final.docx file_size: 65194814 relation: source_file - access_level: open_access checksum: 1b44c57f04d7e8a6fe41b1c9c55a52a3 content_type: application/pdf creator: sshamip date_created: 2020-09-09T11:06:13Z date_updated: 2021-09-11T22:30:05Z embargo: 2021-09-10 file_id: '8352' file_name: Shayan-Thesis-Final.pdf file_size: 23729605 relation: main_file file_date_updated: 2021-09-11T22:30:05Z has_accepted_license: '1' language: - iso: eng month: '09' oa: 1 oa_version: None page: '107' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '7001' relation: part_of_dissertation status: public - id: '6508' relation: part_of_dissertation status: public - id: '735' relation: part_of_dissertation status: public - id: '661' relation: part_of_dissertation status: public status: public supervisor: - first_name: Carl-Philipp J full_name: Heisenberg, Carl-Philipp J id: 39427864-F248-11E8-B48F-1D18A9856A87 last_name: Heisenberg orcid: 0000-0002-0912-4566 - first_name: Björn full_name: Hof, Björn id: 3A374330-F248-11E8-B48F-1D18A9856A87 last_name: Hof orcid: 0000-0003-2057-2754 title: 'Bulk actin dynamics drive phase segregation in zebrafish oocytes ' type: dissertation user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2020' ... --- OA_place: publisher _id: '8620' abstract: - lang: eng text: "The development of the human brain occurs through a tightly regulated series of dynamic and adaptive processes during prenatal and postnatal life. A disruption of this strictly orchestrated series of events can lead to a number of neurodevelopmental conditions, including Autism Spectrum Disorders (ASDs). ASDs are a very common, etiologically and phenotypically heterogeneous group of disorders sharing the core symptoms of social interaction and communication deficits and restrictive and repetitive interests and behaviors. They are estimated to affect one in 59 individuals in the U.S. and, over the last three decades, mutations in more than a hundred genetic loci have been convincingly linked to ASD pathogenesis. Yet, for the vast majority of these ASD-risk genes their role during brain development and precise molecular function still remain elusive.\r\nDe novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin 3 (CUL3) lead to ASD. In the study described here, we used Cul3 mouse models to evaluate the consequences of Cul3 mutations in vivo. Our results show that Cul3 heterozygous knockout mice exhibit deficits in motor coordination as well as ASD-relevant social and cognitive impairments. Cul3+/-, Cul3+/fl Emx1-Cre and Cul3fl/fl Emx1-Cre mutant brains display cortical lamination abnormalities due to defective migration of post-mitotic excitatory neurons, as well as reduced numbers of excitatory and inhibitory neurons. In line with the observed abnormal cortical organization, Cul3 heterozygous deletion is associated with decreased spontaneous excitatory and inhibitory activity in the cortex. At the molecular level we show that Cul3 regulates cytoskeletal and adhesion protein abundance in the mouse embryonic cortex. Abnormal regulation of cytoskeletal proteins in Cul3 mutant neural cells results in atypical organization of the actin mesh at the cell leading edge. Of note, heterozygous deletion of Cul3 in adult mice does not induce the majority of the behavioral defects observed in constitutive Cul3 haploinsufficient animals, pointing to a critical time-window for Cul3 deficiency.\r\nIn conclusion, our data indicate that Cul3 plays a critical role in the regulation of cytoskeletal proteins and neuronal migration. ASD-associated defects and behavioral abnormalities are primarily due to dosage sensitive Cul3 functions at early brain developmental stages." acknowledged_ssus: - _id: Bio - _id: PreCl acknowledgement: I would like to especially thank Armel Nicolas from the Proteomics and Christoph Sommer from the Bioimaging Facilities for the data analysis, and to thank the team of the Preclinical Facility, especially Sabina Deixler, Angela Schlerka, Anita Lepold, Mihalea Mihai and Michael Schun for taking care of the mouse line maintenance and their great support. alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Jasmin full_name: Morandell, Jasmin id: 4739D480-F248-11E8-B48F-1D18A9856A87 last_name: Morandell citation: ama: Morandell J. Illuminating the role of Cul3 in autism spectrum disorder pathogenesis. 2020. doi:10.15479/AT:ISTA:8620 apa: Morandell, J. (2020). Illuminating the role of Cul3 in autism spectrum disorder pathogenesis. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8620 chicago: Morandell, Jasmin. “Illuminating the Role of Cul3 in Autism Spectrum Disorder Pathogenesis.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8620. ieee: J. Morandell, “Illuminating the role of Cul3 in autism spectrum disorder pathogenesis,” Institute of Science and Technology Austria, 2020. ista: Morandell J. 2020. Illuminating the role of Cul3 in autism spectrum disorder pathogenesis. Institute of Science and Technology Austria. mla: Morandell, Jasmin. Illuminating the Role of Cul3 in Autism Spectrum Disorder Pathogenesis. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8620. short: J. Morandell, Illuminating the Role of Cul3 in Autism Spectrum Disorder Pathogenesis, Institute of Science and Technology Austria, 2020. corr_author: '1' date_created: 2020-10-07T14:53:13Z date_published: 2020-10-12T00:00:00Z date_updated: 2026-04-14T09:07:16Z day: '12' ddc: - '610' degree_awarded: PhD department: - _id: GaNo doi: 10.15479/AT:ISTA:8620 file: - access_level: open_access checksum: 7ee83e42de3e5ce2fedb44dff472f75f content_type: application/pdf creator: jmorande date_created: 2020-10-07T14:41:49Z date_updated: 2021-10-16T22:30:04Z embargo: 2021-10-15 file_id: '8621' file_name: Jasmin_Morandell_Thesis-2020_final.pdf file_size: 16155786 relation: main_file - access_level: closed checksum: 5e0464af453734210ce7aab7b4a92e3a content_type: application/x-zip-compressed creator: jmorande date_created: 2020-10-07T14:45:07Z date_updated: 2021-10-16T22:30:04Z embargo_to: open_access file_id: '8622' file_name: Jasmin_Morandell_Thesis-2020_final.zip file_size: 24344152 relation: source_file file_date_updated: 2021-10-16T22:30:04Z has_accepted_license: '1' language: - iso: eng month: '10' oa: 1 oa_version: Published Version page: '138' project: - _id: 2548AE96-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232 name: Molecular Drug Targets - _id: 05A0D778-7A3F-11EA-A408-12923DDC885E grant_number: F7807 name: Stem Cell Modulation in Neural Development and Regeneration/ P07-Neural stem cells in autism and epilepsy publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '7800' relation: part_of_dissertation status: public - id: '8131' relation: part_of_dissertation status: public status: public supervisor: - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 title: Illuminating the role of Cul3 in autism spectrum disorder pathogenesis type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2020' ... --- _id: '8434' abstract: - lang: eng text: 'Efficient migration on adhesive surfaces involves the protrusion of lamellipodial actin networks and their subsequent stabilization by nascent adhesions. The actin-binding protein lamellipodin (Lpd) is thought to play a critical role in lamellipodium protrusion, by delivering Ena/VASP proteins onto the growing plus ends of actin filaments and by interacting with the WAVE regulatory complex, an activator of the Arp2/3 complex, at the leading edge. Using B16-F1 melanoma cell lines, we demonstrate that genetic ablation of Lpd compromises protrusion efficiency and coincident cell migration without altering essential parameters of lamellipodia, including their maximal rate of forward advancement and actin polymerization. We also confirmed lamellipodia and migration phenotypes with CRISPR/Cas9-mediated Lpd knockout Rat2 fibroblasts, excluding cell type-specific effects. Moreover, computer-aided analysis of cell-edge morphodynamics on B16-F1 cell lamellipodia revealed that loss of Lpd correlates with reduced temporal protrusion maintenance as a prerequisite of nascent adhesion formation. We conclude that Lpd optimizes protrusion and nascent adhesion formation by counteracting frequent, chaotic retraction and membrane ruffling.This article has an associated First Person interview with the first author of the paper. ' acknowledgement: This work was supported in part by Deutsche Forschungsgemeinschaft (DFG)[GRK2223/1, RO2414/5-1 (to K.R.), FA350/11-1 (to M.F.) and FA330/11-1 (to J.F.)],as well as by intramural funding from the Helmholtz Association (to T.E.B.S. andK.R.). G.D. was additionally funded by the Austrian Science Fund (FWF) LiseMeitner Program [M-2495]. A.C.H. and M.W. are supported by the Francis CrickInstitute, which receives its core funding from Cancer Research UK [FC001209], theMedical Research Council [FC001209] and the Wellcome Trust [FC001209]. M.K. issupported by the Biotechnology and Biological Sciences Research Council [BB/F011431/1, BB/J000590/1, BB/N000226/1]. Deposited in PMC for release after 6months. article_number: jcs239020 article_processing_charge: No article_type: original author: - first_name: Georgi A full_name: Dimchev, Georgi A id: 38C393BE-F248-11E8-B48F-1D18A9856A87 last_name: Dimchev orcid: 0000-0001-8370-6161 - first_name: Behnam full_name: Amiri, Behnam last_name: Amiri - first_name: Ashley C. full_name: Humphries, Ashley C. last_name: Humphries - first_name: Matthias full_name: Schaks, Matthias last_name: Schaks - first_name: Vanessa full_name: Dimchev, Vanessa last_name: Dimchev - first_name: Theresia E. B. full_name: Stradal, Theresia E. B. last_name: Stradal - first_name: Jan full_name: Faix, Jan last_name: Faix - first_name: Matthias full_name: Krause, Matthias last_name: Krause - first_name: Michael full_name: Way, Michael last_name: Way - first_name: Martin full_name: Falcke, Martin last_name: Falcke - first_name: Klemens full_name: Rottner, Klemens last_name: Rottner citation: ama: Dimchev GA, Amiri B, Humphries AC, et al. Lamellipodin tunes cell migration by stabilizing protrusions and promoting adhesion formation. Journal of Cell Science. 2020;133(7). doi:10.1242/jcs.239020 apa: Dimchev, G. A., Amiri, B., Humphries, A. C., Schaks, M., Dimchev, V., Stradal, T. E. B., … Rottner, K. (2020). Lamellipodin tunes cell migration by stabilizing protrusions and promoting adhesion formation. Journal of Cell Science. The Company of Biologists. https://doi.org/10.1242/jcs.239020 chicago: Dimchev, Georgi A, Behnam Amiri, Ashley C. Humphries, Matthias Schaks, Vanessa Dimchev, Theresia E. B. Stradal, Jan Faix, et al. “Lamellipodin Tunes Cell Migration by Stabilizing Protrusions and Promoting Adhesion Formation.” Journal of Cell Science. The Company of Biologists, 2020. https://doi.org/10.1242/jcs.239020. ieee: G. A. Dimchev et al., “Lamellipodin tunes cell migration by stabilizing protrusions and promoting adhesion formation,” Journal of Cell Science, vol. 133, no. 7. The Company of Biologists, 2020. ista: Dimchev GA, Amiri B, Humphries AC, Schaks M, Dimchev V, Stradal TEB, Faix J, Krause M, Way M, Falcke M, Rottner K. 2020. Lamellipodin tunes cell migration by stabilizing protrusions and promoting adhesion formation. Journal of Cell Science. 133(7), jcs239020. mla: Dimchev, Georgi A., et al. “Lamellipodin Tunes Cell Migration by Stabilizing Protrusions and Promoting Adhesion Formation.” Journal of Cell Science, vol. 133, no. 7, jcs239020, The Company of Biologists, 2020, doi:10.1242/jcs.239020. short: G.A. Dimchev, B. Amiri, A.C. Humphries, M. Schaks, V. Dimchev, T.E.B. Stradal, J. Faix, M. Krause, M. Way, M. Falcke, K. Rottner, Journal of Cell Science 133 (2020). date_created: 2020-09-17T14:00:33Z date_published: 2020-04-09T00:00:00Z date_updated: 2025-04-15T07:52:13Z day: '09' ddc: - '570' department: - _id: FlSc doi: 10.1242/jcs.239020 external_id: isi: - '000534387800005' pmid: - ' 32094266' file: - access_level: open_access checksum: ba917e551acc4ece2884b751434df9ae content_type: application/pdf creator: dernst date_created: 2020-09-17T14:07:51Z date_updated: 2020-10-11T22:30:02Z embargo: 2020-10-10 file_id: '8435' file_name: 2020_JournalCellScience_Dimchev.pdf file_size: 13493302 relation: main_file file_date_updated: 2020-10-11T22:30:02Z has_accepted_license: '1' intvolume: ' 133' isi: 1 issue: '7' keyword: - Cell Biology language: - iso: eng month: '04' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 2674F658-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: M02495 name: Protein structure and function in filopodia across scales publication: Journal of Cell Science publication_identifier: eissn: - 1477-9137 issn: - 0021-9533 publication_status: published publisher: The Company of Biologists quality_controlled: '1' scopus_import: '1' status: public title: Lamellipodin tunes cell migration by stabilizing protrusions and promoting adhesion formation type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 133 year: '2020' ... --- _id: '7800' abstract: - lang: eng text: De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 (CUL3) lead to autism spectrum disorder (ASD). Here, we used Cul3 mouse models to evaluate the consequences of Cul3 mutations in vivo. Our results show that Cul3 haploinsufficient mice exhibit deficits in motor coordination as well as ASD-relevant social and cognitive impairments. Cul3 mutant brain displays cortical lamination abnormalities due to defective neuronal migration and reduced numbers of excitatory and inhibitory neurons. In line with the observed abnormal columnar organization, Cul3 haploinsufficiency is associated with decreased spontaneous excitatory and inhibitory activity in the cortex. At the molecular level, employing a quantitative proteomic approach, we show that Cul3 regulates cytoskeletal and adhesion protein abundance in mouse embryos. Abnormal regulation of cytoskeletal proteins in Cul3 mutant neuronal cells results in atypical organization of the actin mesh at the cell leading edge, likely causing the observed migration deficits. In contrast to these important functions early in development, Cul3 deficiency appears less relevant at adult stages. In fact, induction of Cul3 haploinsufficiency in adult mice does not result in the behavioral defects observed in constitutive Cul3 haploinsufficient animals. Taken together, our data indicate that Cul3 has a critical role in the regulation of cytoskeletal proteins and neuronal migration and that ASD-associated defects and behavioral abnormalities are primarily due to Cul3 functions at early developmental stages. acknowledged_ssus: - _id: PreCl article_processing_charge: No author: - first_name: Jasmin full_name: Morandell, Jasmin id: 4739D480-F248-11E8-B48F-1D18A9856A87 last_name: Morandell - first_name: Lena A full_name: Schwarz, Lena A id: 29A8453C-F248-11E8-B48F-1D18A9856A87 last_name: Schwarz - first_name: Bernadette full_name: Basilico, Bernadette id: 36035796-5ACA-11E9-A75E-7AF2E5697425 last_name: Basilico orcid: 0000-0003-1843-3173 - first_name: Saren full_name: Tasciyan, Saren id: 4323B49C-F248-11E8-B48F-1D18A9856A87 last_name: Tasciyan orcid: 0000-0003-1671-393X - first_name: Armel full_name: Nicolas, Armel id: 2A103192-F248-11E8-B48F-1D18A9856A87 last_name: Nicolas - first_name: Christoph M full_name: Sommer, Christoph M id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87 last_name: Sommer orcid: 0000-0003-1216-9105 - first_name: Caroline full_name: Kreuzinger, Caroline id: 382077BA-F248-11E8-B48F-1D18A9856A87 last_name: Kreuzinger - first_name: Lisa full_name: Knaus, Lisa id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87 last_name: Knaus - first_name: Zoe full_name: Dobler, Zoe id: D23090A2-9057-11EA-883A-A8396FC7A38F last_name: Dobler - first_name: Emanuele full_name: Cacci, Emanuele last_name: Cacci - first_name: Johann G full_name: Danzl, Johann G id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87 last_name: Danzl orcid: 0000-0001-8559-3973 - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 citation: ama: Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv. doi:10.1101/2020.01.10.902064 apa: Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Nicolas, A., Sommer, C. M., … Novarino, G. (n.d.). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.01.10.902064 chicago: Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan, Armel Nicolas, Christoph M Sommer, Caroline Kreuzinger, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2020.01.10.902064 . ieee: J. Morandell et al., “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” bioRxiv. Cold Spring Harbor Laboratory. ista: Morandell J, Schwarz LA, Basilico B, Tasciyan S, Nicolas A, Sommer CM, Kreuzinger C, Knaus L, Dobler Z, Cacci E, Danzl JG, Novarino G. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv, 10.1101/2020.01.10.902064 . mla: Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2020.01.10.902064 . short: J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, A. Nicolas, C.M. Sommer, C. Kreuzinger, L. Knaus, Z. Dobler, E. Cacci, J.G. Danzl, G. Novarino, BioRxiv (n.d.). corr_author: '1' date_created: 2020-05-05T14:31:33Z date_published: 2020-01-11T00:00:00Z date_updated: 2026-06-22T22:30:05Z day: '11' ddc: - '570' department: - _id: JoDa - _id: GaNo - _id: LifeSc doi: '10.1101/2020.01.10.902064 ' file: - access_level: open_access checksum: c6799ab5daba80efe8e2ed63c15f8c81 content_type: application/pdf creator: rsix date_created: 2020-05-05T14:31:19Z date_updated: 2020-07-14T12:48:03Z file_id: '7801' file_name: 2020.01.10.902064v1.full.pdf file_size: 2931370 relation: main_file file_date_updated: 2020-07-14T12:48:03Z has_accepted_license: '1' language: - iso: eng month: '01' oa: 1 oa_version: Preprint project: - _id: 265CB4D0-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: I03600 name: Optical control of synaptic function via adhesion molecules - _id: 2548AE96-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232 name: Molecular Drug Targets publication: bioRxiv publication_status: draft publisher: Cold Spring Harbor Laboratory related_material: record: - id: '9429' relation: later_version status: public - id: '8620' relation: dissertation_contains status: public status: public title: Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2020' ... --- _id: '8131' abstract: - lang: eng text: The possibility to generate construct valid animal models enabled the development and testing of therapeutic strategies targeting the core features of autism spectrum disorders (ASDs). At the same time, these studies highlighted the necessity of identifying sensitive developmental time windows for successful therapeutic interventions. Animal and human studies also uncovered the possibility to stratify the variety of ASDs in molecularly distinct subgroups, potentially facilitating effective treatment design. Here, we focus on the molecular pathways emerging as commonly affected by mutations in diverse ASD-risk genes, on their role during critical windows of brain development and the potential treatments targeting these biological processes. article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Bernadette full_name: Basilico, Bernadette id: 36035796-5ACA-11E9-A75E-7AF2E5697425 last_name: Basilico orcid: 0000-0003-1843-3173 - first_name: Jasmin full_name: Morandell, Jasmin id: 4739D480-F248-11E8-B48F-1D18A9856A87 last_name: Morandell - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 citation: ama: Basilico B, Morandell J, Novarino G. Molecular mechanisms for targeted ASD treatments. Current Opinion in Genetics and Development. 2020;65(12):126-137. doi:10.1016/j.gde.2020.06.004 apa: Basilico, B., Morandell, J., & Novarino, G. (2020). Molecular mechanisms for targeted ASD treatments. Current Opinion in Genetics and Development. Elsevier. https://doi.org/10.1016/j.gde.2020.06.004 chicago: Basilico, Bernadette, Jasmin Morandell, and Gaia Novarino. “Molecular Mechanisms for Targeted ASD Treatments.” Current Opinion in Genetics and Development. Elsevier, 2020. https://doi.org/10.1016/j.gde.2020.06.004. ieee: B. Basilico, J. Morandell, and G. Novarino, “Molecular mechanisms for targeted ASD treatments,” Current Opinion in Genetics and Development, vol. 65, no. 12. Elsevier, pp. 126–137, 2020. ista: Basilico B, Morandell J, Novarino G. 2020. Molecular mechanisms for targeted ASD treatments. Current Opinion in Genetics and Development. 65(12), 126–137. mla: Basilico, Bernadette, et al. “Molecular Mechanisms for Targeted ASD Treatments.” Current Opinion in Genetics and Development, vol. 65, no. 12, Elsevier, 2020, pp. 126–37, doi:10.1016/j.gde.2020.06.004. short: B. Basilico, J. Morandell, G. Novarino, Current Opinion in Genetics and Development 65 (2020) 126–137. corr_author: '1' date_created: 2020-07-19T22:00:58Z date_published: 2020-12-01T00:00:00Z date_updated: 2026-06-22T22:30:05Z day: '01' ddc: - '570' department: - _id: GaNo doi: 10.1016/j.gde.2020.06.004 ec_funded: 1 external_id: isi: - '000598918900019' pmid: - '32659636' file: - access_level: open_access content_type: application/pdf creator: dernst date_created: 2020-07-22T06:47:45Z date_updated: 2020-07-22T06:47:45Z file_id: '8146' file_name: 2020_CurrentOpGenetics_Basilico.pdf file_size: 1381545 relation: main_file success: 1 file_date_updated: 2020-07-22T06:47:45Z has_accepted_license: '1' intvolume: ' 65' isi: 1 issue: '12' language: - iso: eng month: '12' oa: 1 oa_version: Published Version page: 126-137 pmid: 1 project: - _id: 260C2330-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '754411' name: ISTplus - Postdoctoral Fellowships - _id: 2548AE96-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232 name: Molecular Drug Targets - _id: 05A0D778-7A3F-11EA-A408-12923DDC885E grant_number: F7807 name: Stem Cell Modulation in Neural Development and Regeneration/ P07-Neural stem cells in autism and epilepsy publication: Current Opinion in Genetics and Development publication_identifier: eissn: - 1879-0380 issn: - 0959-437X publication_status: published publisher: Elsevier quality_controlled: '1' related_material: record: - id: '8620' relation: dissertation_contains status: public scopus_import: '1' status: public title: Molecular mechanisms for targeted ASD treatments 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: ba8df636-2132-11f1-aed0-ed93e2281fdd volume: 65 year: '2020' ... --- OA_place: publisher _id: '8657' abstract: - lang: eng text: "Synthesis of proteins – translation – is a fundamental process of life. Quantitative studies anchor translation into the context of bacterial physiology and reveal several mathematical relationships, called “growth laws,” which capture physiological feedbacks between protein synthesis and cell growth. Growth laws describe the dependency of the ribosome abundance as a function of growth rate, which can change depending on the growth conditions. Perturbations of translation reveal that bacteria employ a compensatory strategy in which the reduced translation capability results in increased expression of the translation machinery.\r\nPerturbations of translation are achieved in various ways; clinically interesting is the application of translation-targeting antibiotics – translation inhibitors. The antibiotic effects on bacterial physiology are often poorly understood. Bacterial responses to two or more simultaneously applied antibiotics are even more puzzling. The combined antibiotic effect determines the type of drug interaction, which ranges from synergy (the effect is stronger than expected) to antagonism (the effect is weaker) and suppression (one of the drugs loses its potency).\r\nIn the first part of this work, we systematically measure the pairwise interaction network for translation inhibitors that interfere with different steps in translation. We find that the interactions are surprisingly diverse and tend to be more antagonistic. To explore the underlying mechanisms, we begin with a minimal biophysical model of combined antibiotic action. We base this model on the kinetics of antibiotic uptake and binding together with the physiological response described by the growth laws. The biophysical model explains some drug interactions, but not all; it specifically fails to predict suppression.\r\nIn the second part of this work, we hypothesize that elusive suppressive drug interactions result from the interplay between ribosomes halted in different stages of translation. To elucidate this putative mechanism of drug interactions between translation inhibitors, we generate translation bottlenecks genetically using in- ducible control of translation factors that regulate well-defined translation cycle steps. These perturbations accurately mimic antibiotic action and drug interactions, supporting that the interplay of different translation bottlenecks partially causes these interactions.\r\nWe extend this approach by varying two translation bottlenecks simultaneously. This approach reveals the suppression of translocation inhibition by inhibited translation. We rationalize this effect by modeling dense traffic of ribosomes that move on transcripts in a translation factor-mediated manner. This model predicts a dissolution of traffic jams caused by inhibited translocation when the density of ribosome traffic is reduced by lowered initiation. We base this model on the growth laws and quantitative relationships between different translation and growth parameters.\r\nIn the final part of this work, we describe a set of tools aimed at quantification of physiological and translation parameters. We further develop a simple model that directly connects the abundance of a translation factor with the growth rate, which allows us to extract physiological parameters describing initiation. We demonstrate the development of tools for measuring translation rate.\r\nThis thesis showcases how a combination of high-throughput growth rate mea- surements, genetics, and modeling can reveal mechanisms of drug interactions. Furthermore, by a gradual transition from combinations of antibiotics to precise genetic interventions, we demonstrated the equivalency between genetic and chemi- cal perturbations of translation. These findings tile the path for quantitative studies of antibiotic combinations and illustrate future approaches towards the quantitative description of translation." acknowledged_ssus: - _id: LifeSc - _id: M-Shop acknowledgement: I thank Life Science Facilities for their continuous support with providing top-notch laboratory materials, keeping the devices humming, and coordinating the repairs and building of custom-designed laboratory equipment with the MIBA Machine shop. alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Bor full_name: Kavcic, Bor id: 350F91D2-F248-11E8-B48F-1D18A9856A87 last_name: Kavcic orcid: 0000-0001-6041-254X citation: ama: 'Kavcic B. Perturbations of protein synthesis: from antibiotics to genetics and physiology. 2020. doi:10.15479/AT:ISTA:8657' apa: 'Kavcic, B. (2020). Perturbations of protein synthesis: from antibiotics to genetics and physiology. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8657' chicago: 'Kavcic, Bor. “Perturbations of Protein Synthesis: From Antibiotics to Genetics and Physiology.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8657.' ieee: 'B. Kavcic, “Perturbations of protein synthesis: from antibiotics to genetics and physiology,” Institute of Science and Technology Austria, 2020.' ista: 'Kavcic B. 2020. Perturbations of protein synthesis: from antibiotics to genetics and physiology. Institute of Science and Technology Austria.' mla: 'Kavcic, Bor. Perturbations of Protein Synthesis: From Antibiotics to Genetics and Physiology. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8657.' short: 'B. Kavcic, Perturbations of Protein Synthesis: From Antibiotics to Genetics and Physiology, Institute of Science and Technology Austria, 2020.' corr_author: '1' date_created: 2020-10-13T16:46:14Z date_published: 2020-10-14T00:00:00Z date_updated: 2026-04-08T07:27:48Z day: '14' ddc: - '571' - '530' - '570' degree_awarded: PhD department: - _id: GaTk doi: 10.15479/AT:ISTA:8657 file: - access_level: open_access checksum: d708ecd62b6fcc3bc1feb483b8dbe9eb content_type: application/pdf creator: bkavcic date_created: 2020-10-15T06:41:20Z date_updated: 2021-10-07T22:30:03Z embargo: 2021-10-06 file_id: '8663' file_name: kavcicB_thesis202009.pdf file_size: 52636162 relation: main_file - access_level: closed checksum: bb35f2352a04db19164da609f00501f3 content_type: application/zip creator: bkavcic date_created: 2020-10-15T06:41:53Z date_updated: 2021-10-07T22:30:03Z embargo_to: open_access file_id: '8664' file_name: 2020b.zip file_size: 321681247 relation: source_file file_date_updated: 2021-10-07T22:30:03Z has_accepted_license: '1' language: - iso: eng month: '10' oa: 1 oa_version: Published Version page: '271' publication_identifier: isbn: - 978-3-99078-011-4 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '7673' relation: part_of_dissertation status: public - id: '8250' relation: part_of_dissertation status: public status: public supervisor: - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - first_name: Mark Tobias full_name: Bollenbach, Mark Tobias id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87 last_name: Bollenbach orcid: 0000-0003-4398-476X title: 'Perturbations of protein synthesis: from antibiotics to genetics and physiology' type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2020' ... --- _id: '7652' abstract: - lang: eng text: Organisms cope with change by taking advantage of transcriptional regulators. However, when faced with rare environments, the evolution of transcriptional regulators and their promoters may be too slow. Here, we investigate whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. Using real-time monitoring of gene-copy-number mutations in Escherichia coli, we show that gene duplications and amplifications enable adaptation to fluctuating environments by rapidly generating copy-number and, therefore, expression-level polymorphisms. This amplification-mediated gene expression tuning (AMGET) occurs on timescales that are similar to canonical gene regulation and can respond to rapid environmental changes. Mathematical modelling shows that amplifications also tune gene expression in stochastic environments in which transcription-factor-based schemes are hard to evolve or maintain. The fleeting nature of gene amplifications gives rise to a generic population-level mechanism that relies on genetic heterogeneity to rapidly tune the expression of any gene, without leaving any genomic signature. acknowledgement: We thank L. Hurst, N. Barton, M. Pleska, M. Steinrück, B. Kavcic and A. Staron for input on the manuscript, and To. Bergmiller and R. Chait for help with microfluidics experiments. I.T. is a recipient the OMV fellowship. R.G. is a recipient of a DOC (Doctoral Fellowship Programme of the Austrian Academy of Sciences) Fellowship of the Austrian Academy of Sciences. article_processing_charge: No article_type: original author: - first_name: Isabella full_name: Tomanek, Isabella id: 3981F020-F248-11E8-B48F-1D18A9856A87 last_name: Tomanek orcid: 0000-0001-6197-363X - first_name: Rok full_name: Grah, Rok id: 483E70DE-F248-11E8-B48F-1D18A9856A87 last_name: Grah orcid: 0000-0003-2539-3560 - first_name: M. full_name: Lagator, M. last_name: Lagator - first_name: A. M. C. full_name: Andersson, A. M. C. last_name: Andersson - first_name: Jonathan P full_name: Bollback, Jonathan P id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87 last_name: Bollback orcid: 0000-0002-4624-4612 - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 citation: ama: Tomanek I, Grah R, Lagator M, et al. Gene amplification as a form of population-level gene expression regulation. Nature Ecology & Evolution. 2020;4(4):612-625. doi:10.1038/s41559-020-1132-7 apa: Tomanek, I., Grah, R., Lagator, M., Andersson, A. M. C., Bollback, J. P., Tkačik, G., & Guet, C. C. (2020). Gene amplification as a form of population-level gene expression regulation. Nature Ecology & Evolution. Springer Nature. https://doi.org/10.1038/s41559-020-1132-7 chicago: Tomanek, Isabella, Rok Grah, M. Lagator, A. M. C. Andersson, Jonathan P Bollback, Gašper Tkačik, and Calin C Guet. “Gene Amplification as a Form of Population-Level Gene Expression Regulation.” Nature Ecology & Evolution. Springer Nature, 2020. https://doi.org/10.1038/s41559-020-1132-7. ieee: I. Tomanek et al., “Gene amplification as a form of population-level gene expression regulation,” Nature Ecology & Evolution, vol. 4, no. 4. Springer Nature, pp. 612–625, 2020. ista: Tomanek I, Grah R, Lagator M, Andersson AMC, Bollback JP, Tkačik G, Guet CC. 2020. Gene amplification as a form of population-level gene expression regulation. Nature Ecology & Evolution. 4(4), 612–625. mla: Tomanek, Isabella, et al. “Gene Amplification as a Form of Population-Level Gene Expression Regulation.” Nature Ecology & Evolution, vol. 4, no. 4, Springer Nature, 2020, pp. 612–25, doi:10.1038/s41559-020-1132-7. short: I. Tomanek, R. Grah, M. Lagator, A.M.C. Andersson, J.P. Bollback, G. Tkačik, C.C. Guet, Nature Ecology & Evolution 4 (2020) 612–625. date_created: 2020-04-08T15:20:53Z date_published: 2020-04-01T00:00:00Z date_updated: 2026-06-22T22:30:06Z day: '01' ddc: - '570' department: - _id: GaTk - _id: CaGu doi: 10.1038/s41559-020-1132-7 external_id: isi: - '000519008300005' pmid: - '32152532' file: - access_level: open_access checksum: ef3bbf42023e30b2c24a6278025d2040 content_type: application/pdf creator: dernst date_created: 2020-10-09T09:56:01Z date_updated: 2020-10-09T09:56:01Z file_id: '8640' file_name: 2020_NatureEcolEvo_Tomanek.pdf file_size: 745242 relation: main_file success: 1 file_date_updated: 2020-10-09T09:56:01Z has_accepted_license: '1' intvolume: ' 4' isi: 1 issue: '4' language: - iso: eng month: '04' oa: 1 oa_version: Submitted Version page: 612-625 pmid: 1 project: - _id: 267C84F4-B435-11E9-9278-68D0E5697425 name: Biophysically realistic genotype-phenotype maps for regulatory networks publication: Nature Ecology & Evolution publication_identifier: issn: - 2397-334X publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/how-to-thrive-without-gene-regulation/ record: - id: '7016' relation: research_data status: public - id: '7383' relation: research_data status: public - id: '8155' relation: dissertation_contains status: public - id: '8653' relation: used_in_publication status: public scopus_import: '1' status: public title: Gene amplification as a form of population-level gene expression regulation type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 4 year: '2020' ... --- _id: '8250' abstract: - lang: eng text: 'Antibiotics that interfere with translation, when combined, interact in diverse and difficult-to-predict ways. Here, we explain these interactions by “translation bottlenecks”: points in the translation cycle where antibiotics block ribosomal progression. To elucidate the underlying mechanisms of drug interactions between translation inhibitors, we generate translation bottlenecks genetically using inducible control of translation factors that regulate well-defined translation cycle steps. These perturbations accurately mimic antibiotic action and drug interactions, supporting that the interplay of different translation bottlenecks causes these interactions. We further show that growth laws, combined with drug uptake and binding kinetics, enable the direct prediction of a large fraction of observed interactions, yet fail to predict suppression. However, varying two translation bottlenecks simultaneously supports that dense traffic of ribosomes and competition for translation factors account for the previously unexplained suppression. These results highlight the importance of “continuous epistasis” in bacterial physiology.' acknowledgement: "We thank M. Hennessey-Wesen, I. Tomanek, K. Jain, A. Staron, K. Tomasek, M. Scott,\r\nK.C. Huang, and Z. Gitai for reading the manuscript and constructive comments. B.K. is\r\nindebted to C. Guet for additional guidance and generous support, which rendered this\r\nwork possible. B.K. thanks all members of Guet group for many helpful discussions and\r\nsharing of resources. B.K. additionally acknowledges the tremendous support from A.\r\nAngermayr and K. Mitosch with experimental work. We further thank E. Brown for\r\nhelpful comments regarding lamotrigine, and A. Buskirk for valuable suggestions\r\nregarding the ribosome footprint size. This work was supported in part by Austrian\r\nScience Fund (FWF) standalone grants P 27201-B22 (to T.B.) and P 28844 (to G.T.),\r\nHFSP program Grant RGP0042/2013 (to T.B.), German Research Foundation (DFG)\r\nstandalone grant BO 3502/2-1 (to T.B.), and German Research Foundation (DFG)\r\nCollaborative Research Centre (SFB) 1310 (to T.B.). Open access funding provided by\r\nProjekt DEAL." article_number: '4013' article_processing_charge: No article_type: original author: - first_name: Bor full_name: Kavcic, Bor id: 350F91D2-F248-11E8-B48F-1D18A9856A87 last_name: Kavcic orcid: 0000-0001-6041-254X - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - first_name: Tobias full_name: Bollenbach, Tobias id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87 last_name: Bollenbach orcid: 0000-0003-4398-476X citation: ama: Kavcic B, Tkačik G, Bollenbach MT. Mechanisms of drug interactions between translation-inhibiting antibiotics. Nature Communications. 2020;11. doi:10.1038/s41467-020-17734-z apa: Kavcic, B., Tkačik, G., & Bollenbach, M. T. (2020). Mechanisms of drug interactions between translation-inhibiting antibiotics. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-020-17734-z chicago: Kavcic, Bor, Gašper Tkačik, and Mark Tobias Bollenbach. “Mechanisms of Drug Interactions between Translation-Inhibiting Antibiotics.” Nature Communications. Springer Nature, 2020. https://doi.org/10.1038/s41467-020-17734-z. ieee: B. Kavcic, G. Tkačik, and M. T. Bollenbach, “Mechanisms of drug interactions between translation-inhibiting antibiotics,” Nature Communications, vol. 11. Springer Nature, 2020. ista: Kavcic B, Tkačik G, Bollenbach MT. 2020. Mechanisms of drug interactions between translation-inhibiting antibiotics. Nature Communications. 11, 4013. mla: Kavcic, Bor, et al. “Mechanisms of Drug Interactions between Translation-Inhibiting Antibiotics.” Nature Communications, vol. 11, 4013, Springer Nature, 2020, doi:10.1038/s41467-020-17734-z. short: B. Kavcic, G. Tkačik, M.T. Bollenbach, Nature Communications 11 (2020). date_created: 2020-08-12T09:13:50Z date_published: 2020-08-11T00:00:00Z date_updated: 2026-06-22T22:30:06Z day: '11' ddc: - '570' department: - _id: GaTk doi: 10.1038/s41467-020-17734-z external_id: isi: - '000562769300008' pmid: - '32782250' file: - access_level: open_access checksum: 986bebb308850a55850028d3d2b5b664 content_type: application/pdf creator: dernst date_created: 2020-08-17T07:36:57Z date_updated: 2020-08-17T07:36:57Z file_id: '8275' file_name: 2020_NatureComm_Kavcic.pdf file_size: 1965672 relation: main_file success: 1 file_date_updated: 2020-08-17T07:36:57Z has_accepted_license: '1' intvolume: ' 11' isi: 1 language: - iso: eng month: '08' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 25E9AF9E-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P27201-B22 name: Revealing the mechanisms underlying drug interactions - _id: 254E9036-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P28844-B27 name: Biophysics of information processing in gene regulation publication: Nature Communications publication_identifier: issn: - 2041-1723 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: record: - id: '8657' relation: dissertation_contains status: public scopus_import: '1' status: public title: Mechanisms of drug interactions between translation-inhibiting antibiotics 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: 11 year: '2020' ... --- OA_place: publisher _id: '8653' abstract: - lang: eng text: "Mutations are the raw material of evolution and come in many different flavors. Point mutations change a single letter in the DNA sequence, while copy number mutations like duplications or deletions add or remove many letters of the DNA sequence simultaneously. Each type of mutation exhibits specific properties like its rate of formation and reversal. \r\nGene expression is a fundamental phenotype that can be altered by both, point and copy number mutations. The following thesis is concerned with the dynamics of gene expression evolution and how it is affected by the properties exhibited by point and copy number mutations. Specifically, we are considering i) copy number mutations during adaptation to fluctuating environments and ii) the interaction of copy number and point mutations during adaptation to constant environments.  " alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Isabella full_name: Tomanek, Isabella id: 3981F020-F248-11E8-B48F-1D18A9856A87 last_name: Tomanek orcid: 0000-0001-6197-363X citation: ama: Tomanek I. The evolution of gene expression by copy number and point mutations. 2020. doi:10.15479/AT:ISTA:8653 apa: Tomanek, I. (2020). The evolution of gene expression by copy number and point mutations. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8653 chicago: Tomanek, Isabella. “The Evolution of Gene Expression by Copy Number and Point Mutations.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8653. ieee: I. Tomanek, “The evolution of gene expression by copy number and point mutations,” Institute of Science and Technology Austria, 2020. ista: Tomanek I. 2020. The evolution of gene expression by copy number and point mutations. Institute of Science and Technology Austria. mla: Tomanek, Isabella. The Evolution of Gene Expression by Copy Number and Point Mutations. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8653. short: I. Tomanek, The Evolution of Gene Expression by Copy Number and Point Mutations, Institute of Science and Technology Austria, 2020. corr_author: '1' date_created: 2020-10-13T13:02:33Z date_published: 2020-10-13T00:00:00Z date_updated: 2026-04-08T07:29:19Z day: '13' ddc: - '576' degree_awarded: PhD department: - _id: CaGu doi: 10.15479/AT:ISTA:8653 file: - access_level: closed checksum: c01d9f59794b4b70528f37637c17ad02 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: itomanek date_created: 2020-10-16T12:14:21Z date_updated: 2021-10-20T22:30:03Z embargo_to: open_access file_id: '8666' file_name: Thesis_ITomanek_final_201016.docx file_size: 25131884 relation: source_file - access_level: open_access checksum: f8edbc3b0f81a780e13ca1e561d42d8b content_type: application/pdf creator: itomanek date_created: 2020-10-16T12:14:21Z date_updated: 2021-10-20T22:30:03Z embargo: 2021-10-19 file_id: '8667' file_name: Thesis_ITomanek_final_201016.pdf file_size: 15405675 relation: main_file file_date_updated: 2021-10-20T22:30:03Z has_accepted_license: '1' keyword: - duplication - amplification - promoter - CNV - AMGET - experimental evolution - Escherichia coli language: - iso: eng month: '10' oa: 1 oa_version: Published Version page: '117' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '7652' relation: research_data status: public status: public supervisor: - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 title: The evolution of gene expression by copy number and point mutations type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2020' ... --- _id: '7673' abstract: - lang: eng text: Combining drugs can improve the efficacy of treatments. However, predicting the effect of drug combinations is still challenging. The combined potency of drugs determines the drug interaction, which is classified as synergistic, additive, antagonistic, or suppressive. While probabilistic, non-mechanistic models exist, there is currently no biophysical model that can predict antibiotic interactions. Here, we present a physiologically relevant model of the combined action of antibiotics that inhibit protein synthesis by targeting the ribosome. This model captures the kinetics of antibiotic binding and transport, and uses bacterial growth laws to predict growth in the presence of antibiotic combinations. We find that this biophysical model can produce all drug interaction types except suppression. We show analytically that antibiotics which cannot bind to the ribosome simultaneously generally act as substitutes for one another, leading to additive drug interactions. Previously proposed null expectations for higher-order drug interactions follow as a limiting case of our model. We further extend the model to include the effects of direct physical or allosteric interactions between individual drugs on the ribosome. Notably, such direct interactions profoundly change the combined drug effect, depending on the kinetic parameters of the drugs used. The model makes additional predictions for the effects of resistance genes on drug interactions and for interactions between ribosome-targeting antibiotics and antibiotics with other targets. These findings enhance our understanding of the interplay between drug action and cell physiology and are a key step toward a general framework for predicting drug interactions. article_processing_charge: No author: - first_name: Bor full_name: Kavcic, Bor id: 350F91D2-F248-11E8-B48F-1D18A9856A87 last_name: Kavcic orcid: 0000-0001-6041-254X - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - first_name: Tobias full_name: Bollenbach, Tobias id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87 last_name: Bollenbach orcid: 0000-0003-4398-476X citation: ama: Kavcic B, Tkačik G, Bollenbach MT. A minimal biophysical model of combined antibiotic action. bioRxiv. 2020. doi:10.1101/2020.04.18.047886 apa: Kavcic, B., Tkačik, G., & Bollenbach, M. T. (2020). A minimal biophysical model of combined antibiotic action. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.04.18.047886 chicago: Kavcic, Bor, Gašper Tkačik, and Mark Tobias Bollenbach. “A Minimal Biophysical Model of Combined Antibiotic Action.” BioRxiv. Cold Spring Harbor Laboratory, 2020. https://doi.org/10.1101/2020.04.18.047886. ieee: B. Kavcic, G. Tkačik, and M. T. Bollenbach, “A minimal biophysical model of combined antibiotic action,” bioRxiv. Cold Spring Harbor Laboratory, 2020. ista: Kavcic B, Tkačik G, Bollenbach MT. 2020. A minimal biophysical model of combined antibiotic action. bioRxiv, 10.1101/2020.04.18.047886. mla: Kavcic, Bor, et al. “A Minimal Biophysical Model of Combined Antibiotic Action.” BioRxiv, Cold Spring Harbor Laboratory, 2020, doi:10.1101/2020.04.18.047886. short: B. Kavcic, G. Tkačik, M.T. Bollenbach, BioRxiv (2020). date_created: 2020-04-22T08:27:56Z date_published: 2020-04-18T00:00:00Z date_updated: 2026-06-22T22:30:06Z day: '18' department: - _id: GaTk doi: 10.1101/2020.04.18.047886 language: - iso: eng main_file_link: - open_access: '1' url: 'https://doi.org/10.1101/2020.04.18.047886 ' month: '04' oa: 1 oa_version: Preprint project: - _id: 25E9AF9E-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P27201-B22 name: Revealing the mechanisms underlying drug interactions - _id: 254E9036-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P28844-B27 name: Biophysics of information processing in gene regulation publication: bioRxiv publication_status: published publisher: Cold Spring Harbor Laboratory related_material: record: - id: '8997' relation: later_version status: public - id: '8657' relation: dissertation_contains status: public status: public title: A minimal biophysical model of combined antibiotic action type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2020' ... --- _id: '7427' abstract: - lang: eng text: Plants, like other multicellular organisms, survive through a delicate balance between growth and defense against pathogens. Salicylic acid (SA) is a major defense signal in plants, and the perception mechanism as well as downstream signaling activating the immune response are known. Here, we identify a parallel SA signaling that mediates growth attenuation. SA directly binds to A subunits of protein phosphatase 2A (PP2A), inhibiting activity of this complex. Among PP2A targets, the PIN2 auxin transporter is hyperphosphorylated in response to SA, leading to changed activity of this important growth regulator. Accordingly, auxin transport and auxin-mediated root development, including growth, gravitropic response, and lateral root organogenesis, are inhibited. This study reveals how SA, besides activating immunity, concomitantly attenuates growth through crosstalk with the auxin distribution network. Further analysis of this dual role of SA and characterization of additional SA-regulated PP2A targets will provide further insights into mechanisms maintaining a balance between growth and defense. acknowledged_ssus: - _id: Bio - _id: LifeSc acknowledgement: "We thank Shigeyuki Betsuyaku (University of Tsukuba), Alison Delong (Brown University), Xinnian Dong (Duke University), Dolf Weijers (Wageningen University), Yuelin Zhang (UBC), and Martine Pastuglia (Institut Jean-Pierre Bourgin) for sharing published materials; Jana Riederer for help with cantharidin physiological analysis; David Domjan for help with cloning pET28a-PIN2HL; Qing Lu for help with DARTS; Hana Kozubı´kova´ for technical support on SA derivative synthesis; Zuzana Vondra´ kova´ for technical support with tobacco cells; Lucia Strader (Washington University), Bert De Rybel (Ghent University), Bartel Vanholme (Ghent University), and Lukas Mach (BOKU) for helpful discussions; and bioimaging and life science facilities of IST Austria for continuous support. We gratefully acknowledge the Nottingham Arabidopsis Stock Center (NASC) for providing T-DNA insertional mutants. The DSC and SPR instruments were provided by the EQ-BOKU VIBT GmbH and the BOKU Core Facility for Biomolecular and Cellular Analysis, with help of Irene Schaffner. The research leading to these results has received funding from the European Union’s Horizon 2020 program (ERC grant agreement no. 742985 to J.F.) and the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. 291734. S.T. was supported by a European Molecular Biology Organization (EMBO) long-term postdoctoral fellowship (ALTF 723-2015). O.N. was supported by the Ministry of Education, Youth and Sports of the Czech Republic (European Regional Development Fund-Project ‘‘Centre for Experimental Plant Biology’’ no. CZ.02.1.01/0.0/0.0/16_019/0000738). J. Pospısil was supported by European Regional Development Fund Project ‘‘Centre for Experimental Plant Biology’’\r\n(no. CZ.02.1.01/0.0/0.0/16_019/0000738). J. Petrasek was supported by EU Operational Programme Prague-Competitiveness (no. CZ.2.16/3.1.00/21519). " article_processing_charge: No article_type: original author: - first_name: Shutang full_name: Tan, Shutang id: 2DE75584-F248-11E8-B48F-1D18A9856A87 last_name: Tan orcid: 0000-0002-0471-8285 - first_name: Melinda F full_name: Abas, Melinda F id: 3CFB3B1C-F248-11E8-B48F-1D18A9856A87 last_name: Abas - first_name: Inge full_name: Verstraeten, Inge id: 362BF7FE-F248-11E8-B48F-1D18A9856A87 last_name: Verstraeten orcid: 0000-0001-7241-2328 - first_name: Matous full_name: Glanc, Matous id: 1AE1EA24-02D0-11E9-9BAA-DAF4881429F2 last_name: Glanc orcid: 0000-0003-0619-7783 - first_name: Gergely full_name: Molnar, Gergely id: 34F1AF46-F248-11E8-B48F-1D18A9856A87 last_name: Molnar - first_name: Jakub full_name: Hajny, Jakub id: 4800CC20-F248-11E8-B48F-1D18A9856A87 last_name: Hajny orcid: 0000-0003-2140-7195 - first_name: Pavel full_name: Lasák, Pavel last_name: Lasák - first_name: Ivan full_name: Petřík, Ivan last_name: Petřík - first_name: Eugenia full_name: Russinova, Eugenia last_name: Russinova - first_name: Jan full_name: Petrášek, Jan last_name: Petrášek - first_name: Ondřej full_name: Novák, Ondřej last_name: Novák - first_name: Jiří full_name: Pospíšil, Jiří last_name: Pospíšil - first_name: Jiří full_name: Friml, Jiří id: 4159519E-F248-11E8-B48F-1D18A9856A87 last_name: Friml orcid: 0000-0002-8302-7596 citation: ama: Tan S, Abas MF, Verstraeten I, et al. Salicylic acid targets protein phosphatase 2A to attenuate growth in plants. Current Biology. 2020;30(3):381-395.e8. doi:10.1016/j.cub.2019.11.058 apa: Tan, S., Abas, M. F., Verstraeten, I., Glanc, M., Molnar, G., Hajny, J., … Friml, J. (2020). Salicylic acid targets protein phosphatase 2A to attenuate growth in plants. Current Biology. Cell Press. https://doi.org/10.1016/j.cub.2019.11.058 chicago: Tan, Shutang, Melinda F Abas, Inge Verstraeten, Matous Glanc, Gergely Molnar, Jakub Hajny, Pavel Lasák, et al. “Salicylic Acid Targets Protein Phosphatase 2A to Attenuate Growth in Plants.” Current Biology. Cell Press, 2020. https://doi.org/10.1016/j.cub.2019.11.058. ieee: S. Tan et al., “Salicylic acid targets protein phosphatase 2A to attenuate growth in plants,” Current Biology, vol. 30, no. 3. Cell Press, p. 381–395.e8, 2020. ista: Tan S, Abas MF, Verstraeten I, Glanc M, Molnar G, Hajny J, Lasák P, Petřík I, Russinova E, Petrášek J, Novák O, Pospíšil J, Friml J. 2020. Salicylic acid targets protein phosphatase 2A to attenuate growth in plants. Current Biology. 30(3), 381–395.e8. mla: Tan, Shutang, et al. “Salicylic Acid Targets Protein Phosphatase 2A to Attenuate Growth in Plants.” Current Biology, vol. 30, no. 3, Cell Press, 2020, p. 381–395.e8, doi:10.1016/j.cub.2019.11.058. short: S. Tan, M.F. Abas, I. Verstraeten, M. Glanc, G. Molnar, J. Hajny, P. Lasák, I. Petřík, E. Russinova, J. Petrášek, O. Novák, J. Pospíšil, J. Friml, Current Biology 30 (2020) 381–395.e8. corr_author: '1' date_created: 2020-02-02T23:01:00Z date_published: 2020-02-03T00:00:00Z date_updated: 2026-06-22T22:30:07Z day: '03' ddc: - '580' department: - _id: JiFr - _id: EvBe doi: 10.1016/j.cub.2019.11.058 ec_funded: 1 external_id: isi: - '000511287900018' pmid: - '31956021' file: - access_level: open_access checksum: 16f7d51fe28f91c21e4896a2028df40b content_type: application/pdf creator: dernst date_created: 2020-09-22T09:51:28Z date_updated: 2020-09-22T09:51:28Z file_id: '8555' file_name: 2020_CurrentBiology_Tan.pdf file_size: 5360135 relation: main_file success: 1 file_date_updated: 2020-09-22T09:51:28Z has_accepted_license: '1' intvolume: ' 30' isi: 1 issue: '3' language: - iso: eng month: '02' oa: 1 oa_version: Published Version page: 381-395.e8 pmid: 1 project: - _id: 261099A6-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '742985' name: Tracing Evolution of Auxin Transport and Polarity in Plants - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme - _id: 256FEF10-B435-11E9-9278-68D0E5697425 grant_number: 723-2015 name: Molecular Mechanism underlying Salicylic Acid Regulation of Endocytic Trafficking in Arabidopsis publication: Current Biology publication_identifier: issn: - '09609822' publication_status: published publisher: Cell Press quality_controlled: '1' related_material: record: - id: '8822' relation: dissertation_contains status: public scopus_import: '1' status: public title: Salicylic acid targets protein phosphatase 2A to attenuate growth in plants tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 30 year: '2020' ... --- _id: '7500' abstract: - lang: eng text: "Plant survival depends on vascular tissues, which originate in a self‐organizing manner as strands of cells co‐directionally transporting the plant hormone auxin. The latter phenomenon (also known as auxin canalization) is classically hypothesized to be regulated by auxin itself via the effect of this hormone on the polarity of its own intercellular transport. Correlative observations supported this concept, but molecular insights remain limited.\r\nIn the current study, we established an experimental system based on the model Arabidopsis thaliana, which exhibits auxin transport channels and formation of vasculature strands in response to local auxin application.\r\nOur methodology permits the genetic analysis of auxin canalization under controllable experimental conditions. By utilizing this opportunity, we confirmed the dependence of auxin canalization on a PIN‐dependent auxin transport and nuclear, TIR1/AFB‐mediated auxin signaling. We also show that leaf venation and auxin‐mediated PIN repolarization in the root require TIR1/AFB signaling.\r\nFurther studies based on this experimental system are likely to yield better understanding of the mechanisms underlying auxin transport polarization in other developmental contexts." acknowledgement: We thank Mark Estelle, José M. Alonso and the Arabidopsis Stock Centre for providing seeds. We acknowledge the core facility CELLIM of CEITEC supported by the MEYS CR (LM2015062 Czech‐BioImaging) and Plant Sciences Core Facility of CEITEC Masaryk University for help in generating essential data. This project received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement no. 742985) and the Czech Science Foundation GAČR (GA13‐40637S and GA18‐26981S) to JF. JH is the recipient of a DOC Fellowship of the Austrian Academy of Sciences at the Institute of Science and Technology. The authors declare no competing interests. article_processing_charge: No article_type: original author: - first_name: E full_name: Mazur, E last_name: Mazur - first_name: Ivan full_name: Kulik, Ivan id: F0AB3FCE-02D1-11E9-BD0E-99399A5D3DEB last_name: Kulik - first_name: Jakub full_name: Hajny, Jakub id: 4800CC20-F248-11E8-B48F-1D18A9856A87 last_name: Hajny orcid: 0000-0003-2140-7195 - first_name: Jiří full_name: Friml, Jiří id: 4159519E-F248-11E8-B48F-1D18A9856A87 last_name: Friml orcid: 0000-0002-8302-7596 citation: ama: Mazur E, Kulik I, Hajny J, Friml J. Auxin canalization and vascular tissue formation by TIR1/AFB-mediated auxin signaling in arabidopsis. New Phytologist. 2020;226(5):1375-1383. doi:10.1111/nph.16446 apa: Mazur, E., Kulik, I., Hajny, J., & Friml, J. (2020). Auxin canalization and vascular tissue formation by TIR1/AFB-mediated auxin signaling in arabidopsis. New Phytologist. Wiley. https://doi.org/10.1111/nph.16446 chicago: Mazur, E, Ivan Kulik, Jakub Hajny, and Jiří Friml. “Auxin Canalization and Vascular Tissue Formation by TIR1/AFB-Mediated Auxin Signaling in Arabidopsis.” New Phytologist. Wiley, 2020. https://doi.org/10.1111/nph.16446. ieee: E. Mazur, I. Kulik, J. Hajny, and J. Friml, “Auxin canalization and vascular tissue formation by TIR1/AFB-mediated auxin signaling in arabidopsis,” New Phytologist, vol. 226, no. 5. Wiley, pp. 1375–1383, 2020. ista: Mazur E, Kulik I, Hajny J, Friml J. 2020. Auxin canalization and vascular tissue formation by TIR1/AFB-mediated auxin signaling in arabidopsis. New Phytologist. 226(5), 1375–1383. mla: Mazur, E., et al. “Auxin Canalization and Vascular Tissue Formation by TIR1/AFB-Mediated Auxin Signaling in Arabidopsis.” New Phytologist, vol. 226, no. 5, Wiley, 2020, pp. 1375–83, doi:10.1111/nph.16446. short: E. Mazur, I. Kulik, J. Hajny, J. Friml, New Phytologist 226 (2020) 1375–1383. corr_author: '1' date_created: 2020-02-18T10:03:47Z date_published: 2020-06-01T00:00:00Z date_updated: 2026-06-22T22:30:07Z day: '01' ddc: - '580' department: - _id: JiFr doi: 10.1111/nph.16446 ec_funded: 1 external_id: isi: - '000514939700001' pmid: - '31971254' file: - access_level: open_access checksum: 17de728b0205979feb95ce663ba918c2 content_type: application/pdf creator: dernst date_created: 2020-11-20T09:32:10Z date_updated: 2020-11-20T09:32:10Z file_id: '8781' file_name: 2020_NewPhytologist_Mazur.pdf file_size: 2106888 relation: main_file success: 1 file_date_updated: 2020-11-20T09:32:10Z has_accepted_license: '1' intvolume: ' 226' isi: 1 issue: '5' language: - iso: eng month: '06' oa: 1 oa_version: Published Version page: 1375-1383 pmid: 1 project: - _id: 261099A6-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '742985' name: Tracing Evolution of Auxin Transport and Polarity in Plants - _id: 2699E3D2-B435-11E9-9278-68D0E5697425 grant_number: '25239' name: Cell surface receptor complexes for PIN polarity and auxin-mediated development publication: New Phytologist publication_identifier: eissn: - 1469-8137 issn: - 0028-646x publication_status: published publisher: Wiley quality_controlled: '1' related_material: record: - id: '8822' relation: dissertation_contains status: public scopus_import: '1' status: public title: Auxin canalization and vascular tissue formation by TIR1/AFB-mediated auxin signaling in arabidopsis 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: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 226 year: '2020' ... --- OA_place: publisher _id: '8822' abstract: - lang: eng text: "Self-organization is a hallmark of plant development manifested e.g. by intricate leaf vein patterns, flexible formation of vasculature during organogenesis or its regeneration following wounding. Spontaneously arising channels transporting the phytohormone auxin, created by coordinated polar localizations of PIN-FORMED 1 (PIN1) auxin exporter, provide positional cues for these as well as other plant patterning processes. To find regulators acting downstream of auxin and the TIR1/AFB auxin signaling pathway essential for PIN1 coordinated polarization during auxin canalization, we performed microarray experiments. Besides the known components of general PIN polarity maintenance, such as PID and PIP5K kinases, we identified and characterized a new regulator of auxin canalization, the transcription factor WRKY DNA-BINDING PROTEIN 23 (WRKY23).\r\nNext, we designed a subsequent microarray experiment to further uncover other molecular players, downstream of auxin-TIR1/AFB-WRKY23 involved in the regulation of auxin-mediated PIN repolarization. We identified a novel and crucial part of the molecular machinery underlying auxin canalization. The auxin-regulated malectin-type receptor-like kinase CAMEL and the associated leucine-rich repeat receptor-like kinase CANAR target and directly phosphorylate PIN auxin transporters. camel and canar mutants are impaired in PIN1 subcellular trafficking and auxin-mediated repolarization leading to defects in auxin transport, ultimately to leaf venation and vasculature regeneration defects. Our results describe the CAMEL-CANAR receptor complex, which is required for auxin feed-back on its own transport and thus for coordinated tissue polarization during auxin canalization." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Jakub full_name: Hajny, Jakub id: 4800CC20-F248-11E8-B48F-1D18A9856A87 last_name: Hajny orcid: 0000-0003-2140-7195 citation: ama: Hajny J. Identification and characterization of the molecular machinery of auxin-dependent canalization during vasculature formation and regeneration. 2020. doi:10.15479/AT:ISTA:8822 apa: Hajny, J. (2020). Identification and characterization of the molecular machinery of auxin-dependent canalization during vasculature formation and regeneration. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8822 chicago: Hajny, Jakub. “Identification and Characterization of the Molecular Machinery of Auxin-Dependent Canalization during Vasculature Formation and Regeneration.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8822. ieee: J. Hajny, “Identification and characterization of the molecular machinery of auxin-dependent canalization during vasculature formation and regeneration,” Institute of Science and Technology Austria, 2020. ista: Hajny J. 2020. Identification and characterization of the molecular machinery of auxin-dependent canalization during vasculature formation and regeneration. Institute of Science and Technology Austria. mla: Hajny, Jakub. Identification and Characterization of the Molecular Machinery of Auxin-Dependent Canalization during Vasculature Formation and Regeneration. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8822. short: J. Hajny, Identification and Characterization of the Molecular Machinery of Auxin-Dependent Canalization during Vasculature Formation and Regeneration, Institute of Science and Technology Austria, 2020. corr_author: '1' date_created: 2020-12-01T12:38:18Z date_published: 2020-12-01T00:00:00Z date_updated: 2026-06-18T19:02:05Z day: '01' ddc: - '580' degree_awarded: PhD department: - _id: JiFr doi: 10.15479/AT:ISTA:8822 file: - access_level: closed checksum: 210a9675af5e4c78b0b56d920ac82866 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: jhajny date_created: 2020-12-04T07:27:52Z date_updated: 2021-07-16T22:30:03Z embargo_to: open_access file_id: '8919' file_name: Jakub Hajný IST Austria final_JH.docx file_size: 91279806 relation: source_file - access_level: open_access checksum: 1781385b4aa73eba89cc76c6172f71d2 content_type: application/pdf creator: jhajny date_created: 2020-12-09T15:04:41Z date_updated: 2021-12-08T23:30:03Z embargo: 2021-12-07 file_id: '8933' file_name: Jakub Hajný IST Austria final_JH-merged without Science.pdf file_size: 68707697 relation: main_file file_date_updated: 2021-12-08T23:30:03Z has_accepted_license: '1' language: - iso: eng month: '12' oa: 1 oa_version: Published Version page: '249' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '449' relation: part_of_dissertation status: public - id: '7500' relation: part_of_dissertation status: public - id: '7427' relation: part_of_dissertation status: public - id: '191' relation: part_of_dissertation status: public - id: '6260' relation: part_of_dissertation status: public status: public supervisor: - first_name: Jiří full_name: Friml, Jiří id: 4159519E-F248-11E8-B48F-1D18A9856A87 last_name: Friml orcid: 0000-0002-8302-7596 title: Identification and characterization of the molecular machinery of auxin-dependent canalization during vasculature formation and regeneration type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2020' ... --- _id: '8728' abstract: - lang: eng text: Discrete-time Markov Chains (MCs) and Markov Decision Processes (MDPs) are two standard formalisms in system analysis. Their main associated quantitative objectives are hitting probabilities, discounted sum, and mean payoff. Although there are many techniques for computing these objectives in general MCs/MDPs, they have not been thoroughly studied in terms of parameterized algorithms, particularly when treewidth is used as the parameter. This is in sharp contrast to qualitative objectives for MCs, MDPs and graph games, for which treewidth-based algorithms yield significant complexity improvements. In this work, we show that treewidth can also be used to obtain faster algorithms for the quantitative problems. For an MC with n states and m transitions, we show that each of the classical quantitative objectives can be computed in O((n+m)⋅t2) time, given a tree decomposition of the MC with width t. Our results also imply a bound of O(κ⋅(n+m)⋅t2) for each objective on MDPs, where κ is the number of strategy-iteration refinements required for the given input and objective. Finally, we make an experimental evaluation of our new algorithms on low-treewidth MCs and MDPs obtained from the DaCapo benchmark suite. Our experiments show that on low-treewidth MCs and MDPs, our algorithms outperform existing well-established methods by one or more orders of magnitude. alternative_title: - LNCS article_processing_charge: No author: - first_name: Ali full_name: Asadi, Ali last_name: Asadi - first_name: Krishnendu full_name: Chatterjee, Krishnendu id: 2E5DCA20-F248-11E8-B48F-1D18A9856A87 last_name: Chatterjee orcid: 0000-0002-4561-241X - first_name: Amir Kafshdar full_name: Goharshady, Amir Kafshdar id: 391365CE-F248-11E8-B48F-1D18A9856A87 last_name: Goharshady orcid: 0000-0003-1702-6584 - first_name: Kiarash full_name: Mohammadi, Kiarash last_name: Mohammadi - first_name: Andreas full_name: Pavlogiannis, Andreas id: 49704004-F248-11E8-B48F-1D18A9856A87 last_name: Pavlogiannis orcid: 0000-0002-8943-0722 citation: ama: 'Asadi A, Chatterjee K, Goharshady AK, Mohammadi K, Pavlogiannis A. Faster algorithms for quantitative analysis of MCs and MDPs with small treewidth. In: Automated Technology for Verification and Analysis. Vol 12302. Springer Nature; 2020:253-270. doi:10.1007/978-3-030-59152-6_14' apa: 'Asadi, A., Chatterjee, K., Goharshady, A. K., Mohammadi, K., & Pavlogiannis, A. (2020). Faster algorithms for quantitative analysis of MCs and MDPs with small treewidth. In Automated Technology for Verification and Analysis (Vol. 12302, pp. 253–270). Hanoi, Vietnam: Springer Nature. https://doi.org/10.1007/978-3-030-59152-6_14' chicago: Asadi, Ali, Krishnendu Chatterjee, Amir Kafshdar Goharshady, Kiarash Mohammadi, and Andreas Pavlogiannis. “Faster Algorithms for Quantitative Analysis of MCs and MDPs with Small Treewidth.” In Automated Technology for Verification and Analysis, 12302:253–70. Springer Nature, 2020. https://doi.org/10.1007/978-3-030-59152-6_14. ieee: A. Asadi, K. Chatterjee, A. K. Goharshady, K. Mohammadi, and A. Pavlogiannis, “Faster algorithms for quantitative analysis of MCs and MDPs with small treewidth,” in Automated Technology for Verification and Analysis, Hanoi, Vietnam, 2020, vol. 12302, pp. 253–270. ista: 'Asadi A, Chatterjee K, Goharshady AK, Mohammadi K, Pavlogiannis A. 2020. Faster algorithms for quantitative analysis of MCs and MDPs with small treewidth. Automated Technology for Verification and Analysis. ATVA: Automated Technology for Verification and Analysis, LNCS, vol. 12302, 253–270.' mla: Asadi, Ali, et al. “Faster Algorithms for Quantitative Analysis of MCs and MDPs with Small Treewidth.” Automated Technology for Verification and Analysis, vol. 12302, Springer Nature, 2020, pp. 253–70, doi:10.1007/978-3-030-59152-6_14. short: A. Asadi, K. Chatterjee, A.K. Goharshady, K. Mohammadi, A. Pavlogiannis, in:, Automated Technology for Verification and Analysis, Springer Nature, 2020, pp. 253–270. conference: end_date: 2020-10-23 location: Hanoi, Vietnam name: 'ATVA: Automated Technology for Verification and Analysis' start_date: 2020-10-19 date_created: 2020-11-06T07:30:05Z date_published: 2020-10-12T00:00:00Z date_updated: 2026-06-22T22:30:10Z day: '12' ddc: - '000' department: - _id: KrCh doi: 10.1007/978-3-030-59152-6_14 external_id: isi: - '000723555700014' file: - access_level: open_access checksum: ae83f27e5b189d5abc2e7514f1b7e1b5 content_type: application/pdf creator: dernst date_created: 2020-11-06T07:41:03Z date_updated: 2020-11-06T07:41:03Z file_id: '8729' file_name: 2020_LNCS_ATVA_Asadi_accepted.pdf file_size: 726648 relation: main_file success: 1 file_date_updated: 2020-11-06T07:41:03Z has_accepted_license: '1' intvolume: ' 12302' isi: 1 language: - iso: eng month: '10' oa: 1 oa_version: Submitted Version page: 253-270 project: - _id: 25832EC2-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: S 11407_N23 name: Rigorous Systems Engineering - _id: 25892FC0-B435-11E9-9278-68D0E5697425 grant_number: ICT15-003 name: Efficient Algorithms for Computer Aided Verification - _id: 267066CE-B435-11E9-9278-68D0E5697425 name: Quantitative Analysis of Probabilistic Systems with a focus on Crypto-Currencies publication: Automated Technology for Verification and Analysis publication_identifier: eisbn: - '9783030591526' eissn: - 1611-3349 isbn: - '9783030591519' issn: - 0302-9743 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: record: - id: '8934' relation: dissertation_contains status: public scopus_import: '1' status: public title: Faster algorithms for quantitative analysis of MCs and MDPs with small treewidth type: conference user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 12302 year: '2020' ... --- _id: '8089' abstract: - lang: eng text: "We consider the classical problem of invariant generation for programs with polynomial assignments and focus on synthesizing invariants that are a conjunction of strict polynomial inequalities. We present a sound and semi-complete method based on positivstellensaetze, i.e. theorems in semi-algebraic geometry that characterize positive polynomials over a semi-algebraic set.\r\n\r\nOn the theoretical side, the worst-case complexity of our approach is subexponential, whereas the worst-case complexity of the previous complete method (Kapur, ACA 2004) is doubly-exponential. Even when restricted to linear invariants, the best previous complexity for complete invariant generation is exponential (Colon et al, CAV 2003). On the practical side, we reduce the invariant generation problem to quadratic programming (QCLP), which is a classical optimization problem with many industrial solvers. We demonstrate the applicability of our approach by providing experimental results on several academic benchmarks. To the best of our knowledge, the only previous invariant generation method that provides completeness guarantees for invariants consisting of polynomial inequalities is (Kapur, ACA 2004), which relies on quantifier elimination and cannot even handle toy programs such as our running example." article_processing_charge: No arxiv: 1 author: - first_name: Krishnendu full_name: Chatterjee, Krishnendu id: 2E5DCA20-F248-11E8-B48F-1D18A9856A87 last_name: Chatterjee orcid: 0000-0002-4561-241X - first_name: Hongfei full_name: Fu, Hongfei id: 3AAD03D6-F248-11E8-B48F-1D18A9856A87 last_name: Fu - first_name: Amir Kafshdar full_name: Goharshady, Amir Kafshdar id: 391365CE-F248-11E8-B48F-1D18A9856A87 last_name: Goharshady orcid: 0000-0003-1702-6584 - first_name: Ehsan Kafshdar full_name: Goharshady, Ehsan Kafshdar last_name: Goharshady citation: ama: 'Chatterjee K, Fu H, Goharshady AK, Goharshady EK. Polynomial invariant generation for non-deterministic recursive programs. In: Proceedings of the 41st ACM SIGPLAN Conference on Programming Language Design and Implementation. Association for Computing Machinery; 2020:672-687. doi:10.1145/3385412.3385969' apa: 'Chatterjee, K., Fu, H., Goharshady, A. K., & Goharshady, E. K. (2020). Polynomial invariant generation for non-deterministic recursive programs. In Proceedings of the 41st ACM SIGPLAN Conference on Programming Language Design and Implementation (pp. 672–687). London, United Kingdom: Association for Computing Machinery. https://doi.org/10.1145/3385412.3385969' chicago: Chatterjee, Krishnendu, Hongfei Fu, Amir Kafshdar Goharshady, and Ehsan Kafshdar Goharshady. “Polynomial Invariant Generation for Non-Deterministic Recursive Programs.” In Proceedings of the 41st ACM SIGPLAN Conference on Programming Language Design and Implementation, 672–87. Association for Computing Machinery, 2020. https://doi.org/10.1145/3385412.3385969. ieee: K. Chatterjee, H. Fu, A. K. Goharshady, and E. K. Goharshady, “Polynomial invariant generation for non-deterministic recursive programs,” in Proceedings of the 41st ACM SIGPLAN Conference on Programming Language Design and Implementation, London, United Kingdom, 2020, pp. 672–687. ista: 'Chatterjee K, Fu H, Goharshady AK, Goharshady EK. 2020. Polynomial invariant generation for non-deterministic recursive programs. Proceedings of the 41st ACM SIGPLAN Conference on Programming Language Design and Implementation. PLDI: Programming Language Design and Implementation, 672–687.' mla: Chatterjee, Krishnendu, et al. “Polynomial Invariant Generation for Non-Deterministic Recursive Programs.” Proceedings of the 41st ACM SIGPLAN Conference on Programming Language Design and Implementation, Association for Computing Machinery, 2020, pp. 672–87, doi:10.1145/3385412.3385969. short: K. Chatterjee, H. Fu, A.K. Goharshady, E.K. Goharshady, in:, Proceedings of the 41st ACM SIGPLAN Conference on Programming Language Design and Implementation, Association for Computing Machinery, 2020, pp. 672–687. conference: end_date: 2020-06-20 location: London, United Kingdom name: 'PLDI: Programming Language Design and Implementation' start_date: 2020-06-15 date_created: 2020-07-05T22:00:45Z date_published: 2020-06-11T00:00:00Z date_updated: 2026-06-22T22:30:10Z day: '11' department: - _id: KrCh doi: 10.1145/3385412.3385969 external_id: arxiv: - '1902.04373' isi: - '000614622300045' isi: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://arxiv.org/abs/1902.04373 month: '06' oa: 1 oa_version: Preprint page: 672-687 project: - _id: 25832EC2-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: S 11407_N23 name: Rigorous Systems Engineering - _id: 25892FC0-B435-11E9-9278-68D0E5697425 grant_number: ICT15-003 name: Efficient Algorithms for Computer Aided Verification publication: Proceedings of the 41st ACM SIGPLAN Conference on Programming Language Design and Implementation publication_identifier: isbn: - '9781450376136' publication_status: published publisher: Association for Computing Machinery quality_controlled: '1' related_material: record: - id: '8934' relation: dissertation_contains status: public scopus_import: '1' status: public title: Polynomial invariant generation for non-deterministic recursive programs type: conference user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2020' ... --- _id: '7810' abstract: - lang: eng text: "Interprocedural data-flow analyses form an expressive and useful paradigm of numerous static analysis applications, such as live variables analysis, alias analysis and null pointers analysis. The most widely-used framework for interprocedural data-flow analysis is IFDS, which encompasses distributive data-flow functions over a finite domain. On-demand data-flow analyses restrict the focus of the analysis on specific program locations and data facts. This setting provides a natural split between (i) an offline (or preprocessing) phase, where the program is partially analyzed and analysis summaries are created, and (ii) an online (or query) phase, where analysis queries arrive on demand and the summaries are used to speed up answering queries.\r\nIn this work, we consider on-demand IFDS analyses where the queries concern program locations of the same procedure (aka same-context queries). We exploit the fact that flow graphs of programs have low treewidth to develop faster algorithms that are space and time optimal for many common data-flow analyses, in both the preprocessing and the query phase. We also use treewidth to develop query solutions that are embarrassingly parallelizable, i.e. the total work for answering each query is split to a number of threads such that each thread performs only a constant amount of work. Finally, we implement a static analyzer based on our algorithms, and perform a series of on-demand analysis experiments on standard benchmarks. Our experimental results show a drastic speed-up of the queries after only a lightweight preprocessing phase, which significantly outperforms existing techniques." alternative_title: - LNCS article_processing_charge: No author: - first_name: Krishnendu full_name: Chatterjee, Krishnendu id: 2E5DCA20-F248-11E8-B48F-1D18A9856A87 last_name: Chatterjee orcid: 0000-0002-4561-241X - first_name: Amir Kafshdar full_name: Goharshady, Amir Kafshdar id: 391365CE-F248-11E8-B48F-1D18A9856A87 last_name: Goharshady orcid: 0000-0003-1702-6584 - first_name: Rasmus full_name: Ibsen-Jensen, Rasmus id: 3B699956-F248-11E8-B48F-1D18A9856A87 last_name: Ibsen-Jensen orcid: 0000-0003-4783-0389 - first_name: Andreas full_name: Pavlogiannis, Andreas id: 49704004-F248-11E8-B48F-1D18A9856A87 last_name: Pavlogiannis orcid: 0000-0002-8943-0722 citation: ama: 'Chatterjee K, Goharshady AK, Ibsen-Jensen R, Pavlogiannis A. Optimal and perfectly parallel algorithms for on-demand data-flow analysis. In: European Symposium on Programming. Vol 12075. Springer Nature; 2020:112-140. doi:10.1007/978-3-030-44914-8_5' apa: 'Chatterjee, K., Goharshady, A. K., Ibsen-Jensen, R., & Pavlogiannis, A. (2020). Optimal and perfectly parallel algorithms for on-demand data-flow analysis. In European Symposium on Programming (Vol. 12075, pp. 112–140). Dublin, Ireland: Springer Nature. https://doi.org/10.1007/978-3-030-44914-8_5' chicago: Chatterjee, Krishnendu, Amir Kafshdar Goharshady, Rasmus Ibsen-Jensen, and Andreas Pavlogiannis. “Optimal and Perfectly Parallel Algorithms for On-Demand Data-Flow Analysis.” In European Symposium on Programming, 12075:112–40. Springer Nature, 2020. https://doi.org/10.1007/978-3-030-44914-8_5. ieee: K. Chatterjee, A. K. Goharshady, R. Ibsen-Jensen, and A. Pavlogiannis, “Optimal and perfectly parallel algorithms for on-demand data-flow analysis,” in European Symposium on Programming, Dublin, Ireland, 2020, vol. 12075, pp. 112–140. ista: 'Chatterjee K, Goharshady AK, Ibsen-Jensen R, Pavlogiannis A. 2020. Optimal and perfectly parallel algorithms for on-demand data-flow analysis. European Symposium on Programming. ESOP: Programming Languages and Systems, LNCS, vol. 12075, 112–140.' mla: Chatterjee, Krishnendu, et al. “Optimal and Perfectly Parallel Algorithms for On-Demand Data-Flow Analysis.” European Symposium on Programming, vol. 12075, Springer Nature, 2020, pp. 112–40, doi:10.1007/978-3-030-44914-8_5. short: K. Chatterjee, A.K. Goharshady, R. Ibsen-Jensen, A. Pavlogiannis, in:, European Symposium on Programming, Springer Nature, 2020, pp. 112–140. conference: end_date: 2020-04-30 location: Dublin, Ireland name: 'ESOP: Programming Languages and Systems' start_date: 2020-04-25 corr_author: '1' date_created: 2020-05-10T22:00:50Z date_published: 2020-04-18T00:00:00Z date_updated: 2026-06-22T22:30:11Z day: '18' ddc: - '000' department: - _id: KrCh doi: 10.1007/978-3-030-44914-8_5 external_id: isi: - '000681656800005' file: - access_level: open_access checksum: 8618b80f4cf7b39a60e61a6445ad9807 content_type: application/pdf creator: dernst date_created: 2020-05-26T13:34:48Z date_updated: 2020-07-14T12:48:03Z file_id: '7895' file_name: 2020_LNCS_Chatterjee.pdf file_size: 651250 relation: main_file file_date_updated: 2020-07-14T12:48:03Z has_accepted_license: '1' intvolume: ' 12075' isi: 1 language: - iso: eng month: '04' oa: 1 oa_version: Published Version page: 112-140 project: - _id: 25832EC2-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: S 11407_N23 name: Rigorous Systems Engineering - _id: 25892FC0-B435-11E9-9278-68D0E5697425 grant_number: ICT15-003 name: Efficient Algorithms for Computer Aided Verification - _id: 266EEEC0-B435-11E9-9278-68D0E5697425 name: Quantitative Game-theoretic Analysis of Blockchain Applications and Smart Contracts - _id: 267066CE-B435-11E9-9278-68D0E5697425 name: Quantitative Analysis of Probabilistic Systems with a focus on Crypto-Currencies publication: European Symposium on Programming publication_identifier: eissn: - 1611-3349 isbn: - '9783030449131' issn: - 0302-9743 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: record: - id: '8934' relation: dissertation_contains status: public scopus_import: '1' status: public title: Optimal and perfectly parallel algorithms for on-demand data-flow analysis 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: conference user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd volume: 12075 year: '2020' ... --- OA_place: publisher _id: '8983' abstract: - lang: eng text: Metabolic adaptation is a critical feature of migrating cells. It tunes the metabolic programs of migrating cells to allow them to efficiently exert their crucial roles in development, inflammatory responses and tumor metastasis. Cell migration through physically challenging contexts requires energy. However, how the metabolic reprogramming that underlies in vivo cell invasion is controlled is still unanswered. In my PhD project, I identify a novel conserved metabolic shift in Drosophila melanogaster immune cells that by modulating their bioenergetic potential controls developmentally programmed tissue invasion. We show that this regulation requires a novel conserved nuclear protein, named Atossa. Atossa enhances the transcription of a set of proteins, including an RNA helicase Porthos and two metabolic enzymes, each of which increases the tissue invasion of leading Drosophila macrophages and can rescue the atossa mutant phenotype. Porthos selectively regulates the translational efficiency of a subset of mRNAs containing a 5’-UTR cis-regulatory TOP-like sequence. These 5’TOPL mRNA targets encode mitochondrial-related proteins, including subunits of mitochondrial oxidative phosphorylation (OXPHOS) components III and V and other metabolic-related proteins. Porthos powers up mitochondrial OXPHOS to engender a sufficient ATP supply, which is required for tissue invasion of leading macrophages. Atossa’s two vertebrate orthologs rescue the invasion defect. In my PhD project, I elucidate that Atossa displays a conserved developmental metabolic control to modulate metabolic capacities and the cellular energy state, through altered transcription and translation, to aid the tissue infiltration of leading cells into energy demanding barriers. acknowledged_ssus: - _id: Bio - _id: LifeSc - _id: E-Lib - _id: CampIT acknowledgement: Also, I would like to express my appreciation and thanks to the Bioimaging facility, LSF, GSO, library, and IT people at IST Austria. alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Shamsi full_name: Emtenani, Shamsi id: 49D32318-F248-11E8-B48F-1D18A9856A87 last_name: Emtenani orcid: 0000-0001-6981-6938 citation: ama: Emtenani S. Metabolic regulation of Drosophila macrophage tissue invasion. 2020. doi:10.15479/AT:ISTA:8983 apa: Emtenani, S. (2020). Metabolic regulation of Drosophila macrophage tissue invasion. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8983 chicago: Emtenani, Shamsi. “Metabolic Regulation of Drosophila Macrophage Tissue Invasion.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8983. ieee: S. Emtenani, “Metabolic regulation of Drosophila macrophage tissue invasion,” Institute of Science and Technology Austria, 2020. ista: Emtenani S. 2020. Metabolic regulation of Drosophila macrophage tissue invasion. Institute of Science and Technology Austria. mla: Emtenani, Shamsi. Metabolic Regulation of Drosophila Macrophage Tissue Invasion. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8983. short: S. Emtenani, Metabolic Regulation of Drosophila Macrophage Tissue Invasion, Institute of Science and Technology Austria, 2020. corr_author: '1' date_created: 2020-12-30T15:41:26Z date_published: 2020-12-30T00:00:00Z date_updated: 2026-04-08T07:28:54Z day: '30' ddc: - '570' degree_awarded: PhD department: - _id: DaSi doi: 10.15479/AT:ISTA:8983 file: - access_level: open_access checksum: ec2797ab7a6f253b35df0572b36d1b43 content_type: application/pdf creator: semtenan date_created: 2020-12-30T15:34:01Z date_updated: 2021-12-31T23:30:04Z embargo: 2021-12-30 file_id: '8984' file_name: Thesis_Shamsi_Emtenani_pdfA.pdf file_size: 10848175 relation: main_file - access_level: closed checksum: cc30e6608a9815414024cf548dff3b3a content_type: application/pdf creator: semtenan date_created: 2020-12-30T15:37:36Z date_updated: 2021-12-31T23:30:04Z embargo_to: open_access file_id: '8985' file_name: Thesis_Shamsi_Emtenani_source file.pdf file_size: 10073648 relation: source_file file_date_updated: 2021-12-31T23:30:04Z has_accepted_license: '1' language: - iso: eng month: '12' oa: 1 oa_version: Published Version page: '141' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '8557' relation: part_of_dissertation status: public - id: '6187' relation: part_of_dissertation status: public status: public supervisor: - first_name: Daria E full_name: Siekhaus, Daria E id: 3D224B9E-F248-11E8-B48F-1D18A9856A87 last_name: Siekhaus orcid: 0000-0001-8323-8353 title: Metabolic regulation of Drosophila macrophage tissue invasion type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2020' ... --- _id: '8557' abstract: - lang: eng text: The infiltration of immune cells into tissues underlies the establishment of tissue resident macrophages, and responses to infections and tumors. Yet the mechanisms immune cells utilize to negotiate tissue barriers in living organisms are not well understood, and a role for cortical actin has not been examined. Here we find that the tissue invasion of Drosophila macrophages, also known as plasmatocytes or hemocytes, utilizes enhanced cortical F-actin levels stimulated by the Drosophila member of the fos proto oncogene transcription factor family (Dfos, Kayak). RNA sequencing analysis and live imaging show that Dfos enhances F-actin levels around the entire macrophage surface by increasing mRNA levels of the membrane spanning molecular scaffold tetraspanin TM4SF, and the actin cross-linking filamin Cheerio which are themselves required for invasion. Cortical F-actin levels are critical as expressing a dominant active form of Diaphanous, a actin polymerizing Formin, can rescue the Dfos Dominant Negative macrophage invasion defect. In vivo imaging shows that Dfos is required to enhance the efficiency of the initial phases of macrophage tissue entry. Genetic evidence argues that this Dfos-induced program in macrophages counteracts the constraint produced by the tension of surrounding tissues and buffers the mechanical properties of the macrophage nucleus from affecting tissue entry. We thus identify tuning the cortical actin cytoskeleton through Dfos as a key process allowing efficient forward movement of an immune cell into surrounding tissues. acknowledged_ssus: - _id: LifeSc acknowledgement: 'We thank the following for their contributions: The Drosophila Genomics Resource Center supported by NIH grant 2P40OD010949-10A1 for plasmids, K. Brueckner. B. Stramer, M. Uhlirova, O. Schuldiner, the Bloomington Drosophila Stock Center supported by NIH grant P40OD018537 and the Vienna Drosophila Resource Center for fly stocks, FlyBase (Thurmond et al., 2019) for essential genomic information, and the BDGP in situ database for data (Tomancak et al., 2002, 2007). For antibodies, we thank the Developmental Studies Hybridoma Bank, which was created by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the NIH, and is maintained at the University of Iowa, as well as J. Zeitlinger for her generous gift of Dfos antibody. We thank the Vienna BioCenter Core Facilities for RNA sequencing and analysis and the Life Scientific Service Units at IST Austria for technical support and assistance with microscopy and FACS analysis. We thank C.P. Heisenberg, P. Martin, M. Sixt and Siekhaus group members for discussions and T.Hurd, A. Ratheesh and P. Rangan for comments on the manuscript. A.G. was supported by the Austrian Science Fund (FWF) grant DASI_FWF01_P29638S, D.E.S. by Marie Curie CIG 334077/IRTIM. M.S. is supported by the FWF, PhD program W1212 915 and the European Research Council (ERC) Advanced grant (ERC-2015-AdG TNT-Tumors 694883). S.W. is supported by an OEAW, DOC fellowship.' article_processing_charge: No author: - first_name: Vera full_name: Belyaeva, Vera id: 47F080FE-F248-11E8-B48F-1D18A9856A87 last_name: Belyaeva - first_name: Stephanie full_name: Wachner, Stephanie id: 2A95E7B0-F248-11E8-B48F-1D18A9856A87 last_name: Wachner - first_name: Igor full_name: Gridchyn, Igor id: 4B60654C-F248-11E8-B48F-1D18A9856A87 last_name: Gridchyn orcid: 0000-0002-1807-1929 - first_name: Markus full_name: Linder, Markus last_name: Linder - first_name: Shamsi full_name: Emtenani, Shamsi id: 49D32318-F248-11E8-B48F-1D18A9856A87 last_name: Emtenani orcid: 0000-0001-6981-6938 - first_name: Attila full_name: György, Attila id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87 last_name: György orcid: 0000-0002-1819-198X - first_name: Maria full_name: Sibilia, Maria last_name: Sibilia - first_name: Daria E full_name: Siekhaus, Daria E id: 3D224B9E-F248-11E8-B48F-1D18A9856A87 last_name: Siekhaus orcid: 0000-0001-8323-8353 citation: ama: Belyaeva V, Wachner S, Gridchyn I, et al. Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance. bioRxiv. doi:10.1101/2020.09.18.301481 apa: Belyaeva, V., Wachner, S., Gridchyn, I., Linder, M., Emtenani, S., György, A., … Siekhaus, D. E. (n.d.). Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance. bioRxiv. https://doi.org/10.1101/2020.09.18.301481 chicago: Belyaeva, Vera, Stephanie Wachner, Igor Gridchyn, Markus Linder, Shamsi Emtenani, Attila György, Maria Sibilia, and Daria E Siekhaus. “Cortical Actin Properties Controlled by Drosophila Fos Aid Macrophage Infiltration against Surrounding Tissue Resistance.” BioRxiv, n.d. https://doi.org/10.1101/2020.09.18.301481. ieee: V. Belyaeva et al., “Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance,” bioRxiv. . ista: Belyaeva V, Wachner S, Gridchyn I, Linder M, Emtenani S, György A, Sibilia M, Siekhaus DE. Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance. bioRxiv, 10.1101/2020.09.18.301481. mla: Belyaeva, Vera, et al. “Cortical Actin Properties Controlled by Drosophila Fos Aid Macrophage Infiltration against Surrounding Tissue Resistance.” BioRxiv, doi:10.1101/2020.09.18.301481. short: V. Belyaeva, S. Wachner, I. Gridchyn, M. Linder, S. Emtenani, A. György, M. Sibilia, D.E. Siekhaus, BioRxiv (n.d.). corr_author: '1' date_created: 2020-09-23T09:36:47Z date_published: 2020-09-18T00:00:00Z date_updated: 2026-06-22T22:30:11Z day: '18' department: - _id: DaSi - _id: JoCs doi: 10.1101/2020.09.18.301481 ec_funded: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1101/2020.09.18.301481 month: '09' oa: 1 oa_version: Preprint project: - _id: 253B6E48-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P29638 name: The role of Drosophila TNF alpha in immune cell invasion - _id: 2536F660-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '334077' name: Investigating the role of transporters in invasive migration through junctions - _id: 26199CA4-B435-11E9-9278-68D0E5697425 grant_number: '24800' name: Implications of a TGFβ/Dpp-activated subpopulation for Drosophila macrophage migration publication: bioRxiv publication_status: draft related_material: record: - id: '10614' relation: later_version status: public - id: '8983' relation: dissertation_contains status: public status: public title: Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2020' ...