[{"article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa_version":"Published Version","type":"journal_article","date_updated":"2023-08-22T08:20:11Z","day":"23","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"ec_funded":1,"has_accepted_license":"1","department":[{"_id":"SiHi"}],"language":[{"iso":"eng"}],"doi":"10.1016/j.neuron.2020.06.031","acknowledgement":"We thank A. Heger (IST Austria Preclinical Facility), A. Sommer and C. Czepe (VBCF GmbH, NGS Unit), and A. Seitz and P. Moll (Lexogen GmbH) for technical support; G. Arque, S. Resch, C. Igler, C. Dotter, C. Yahya, Q. Hudson, and D. Andergassen for initial experiments and/or assistance; D. Barlow, O. Bell, and all members of the Hippenmeyer lab for discussion; and N. Barton, B. Vicoso, M. Sixt, and L. Luo for comments on earlier versions of the manuscript. This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Bioimaging Facilities (BIF), Life Science Facilities (LSF), and Preclinical Facilities (PCF). A.H.H. is a recipient of a DOC fellowship (24812) of the Austrian Academy of Sciences. N.A. received support from the FWF Firnberg-Programm (T 1031). R.B. received support from the FWF Meitner-Programm (M 2416). This work was also supported by IST Austria institutional funds; a NÖ Forschung und Bildung n[f+b] life science call grant (C13-002) to S.H.; a program grant from the Human Frontiers Science Program (RGP0053/2014) to S.H.; the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement 618444 to S.H.; and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement 725780 LinPro) to S.H.","external_id":{"isi":["000579698700006"]},"file":[{"access_level":"open_access","file_name":"2020_Neuron_Laukoter.pdf","checksum":"7becdc16a6317304304631087ae7dd7f","file_id":"8828","date_updated":"2020-12-02T09:26:46Z","success":1,"file_size":8911830,"creator":"dernst","content_type":"application/pdf","date_created":"2020-12-02T09:26:46Z","relation":"main_file"}],"date_published":"2020-09-23T00:00:00Z","page":"1160-1179.e9","scopus_import":"1","publication_identifier":{"issn":["0896-6273"]},"citation":{"ista":"Laukoter S, Pauler F, Beattie RJ, Amberg N, Hansen AH, Streicher C, Penz T, Bock C, Hippenmeyer S. 2020. Cell-type specificity of genomic imprinting in cerebral cortex. Neuron. 107(6), 1160–1179.e9.","short":"S. Laukoter, F. Pauler, R.J. Beattie, N. Amberg, A.H. Hansen, C. Streicher, T. Penz, C. Bock, S. Hippenmeyer, Neuron 107 (2020) 1160–1179.e9.","chicago":"Laukoter, Susanne, Florian Pauler, Robert J Beattie, Nicole Amberg, Andi H Hansen, Carmen Streicher, Thomas Penz, Christoph Bock, and Simon Hippenmeyer. “Cell-Type Specificity of Genomic Imprinting in Cerebral Cortex.” <i>Neuron</i>. Elsevier, 2020. <a href=\"https://doi.org/10.1016/j.neuron.2020.06.031\">https://doi.org/10.1016/j.neuron.2020.06.031</a>.","ama":"Laukoter S, Pauler F, Beattie RJ, et al. Cell-type specificity of genomic imprinting in cerebral cortex. <i>Neuron</i>. 2020;107(6):1160-1179.e9. doi:<a href=\"https://doi.org/10.1016/j.neuron.2020.06.031\">10.1016/j.neuron.2020.06.031</a>","ieee":"S. Laukoter <i>et al.</i>, “Cell-type specificity of genomic imprinting in cerebral cortex,” <i>Neuron</i>, vol. 107, no. 6. Elsevier, p. 1160–1179.e9, 2020.","apa":"Laukoter, S., Pauler, F., Beattie, R. J., Amberg, N., Hansen, A. H., Streicher, C., … Hippenmeyer, S. (2020). Cell-type specificity of genomic imprinting in cerebral cortex. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2020.06.031\">https://doi.org/10.1016/j.neuron.2020.06.031</a>","mla":"Laukoter, Susanne, et al. “Cell-Type Specificity of Genomic Imprinting in Cerebral Cortex.” <i>Neuron</i>, vol. 107, no. 6, Elsevier, 2020, p. 1160–1179.e9, doi:<a href=\"https://doi.org/10.1016/j.neuron.2020.06.031\">10.1016/j.neuron.2020.06.031</a>."},"quality_controlled":"1","author":[{"last_name":"Laukoter","first_name":"Susanne","orcid":"0000-0002-7903-3010","full_name":"Laukoter, Susanne","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Florian","last_name":"Pauler","full_name":"Pauler, Florian","orcid":"0000-0002-7462-0048","id":"48EA0138-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Robert J","last_name":"Beattie","full_name":"Beattie, Robert J","orcid":"0000-0002-8483-8753","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Amberg, Nicole","orcid":"0000-0002-3183-8207","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","first_name":"Nicole","last_name":"Amberg"},{"id":"38853E16-F248-11E8-B48F-1D18A9856A87","full_name":"Hansen, Andi H","last_name":"Hansen","first_name":"Andi H"},{"full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","first_name":"Carmen","last_name":"Streicher"},{"last_name":"Penz","first_name":"Thomas","full_name":"Penz, Thomas"},{"last_name":"Bock","first_name":"Christoph","full_name":"Bock, Christoph","orcid":"0000-0001-6091-3088"},{"full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon","last_name":"Hippenmeyer"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png"},"year":"2020","title":"Cell-type specificity of genomic imprinting in cerebral cortex","publication":"Neuron","_id":"8162","ddc":["570"],"oa":1,"related_material":{"link":[{"relation":"press_release","url":"https://ist.ac.at/en/news/cells-react-differently-to-genomic-imprinting/","description":"News on IST Website"}]},"project":[{"grant_number":"24812","name":"Molecular Mechanisms of Radial Neuronal Migration","_id":"2625A13E-B435-11E9-9278-68D0E5697425"},{"grant_number":"T0101031","name":"Role of Eed in neural stem cell lineage progression","_id":"268F8446-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"call_identifier":"FWF","_id":"264E56E2-B435-11E9-9278-68D0E5697425","grant_number":"M02416","name":"Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex"},{"_id":"25D92700-B435-11E9-9278-68D0E5697425","grant_number":"LS13-002","name":"Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain"},{"name":"Quantitative Structure-Function Analysis of Cerebral Cortex Assembly at Clonal Level","grant_number":"RGP0053/2014","_id":"25D7962E-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FP7","_id":"25D61E48-B435-11E9-9278-68D0E5697425","grant_number":"618444","name":"Molecular Mechanisms of Cerebral Cortex Development"},{"_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780"}],"abstract":[{"lang":"eng","text":"In mammalian genomes, a subset of genes is regulated by genomic imprinting, resulting in silencing of one parental allele. Imprinting is essential for cerebral cortex development, but prevalence and functional impact in individual cells is unclear. Here, we determined allelic expression in cortical cell types and established a quantitative platform to interrogate imprinting in single cells. We created cells with uniparental chromosome disomy (UPD) containing two copies of either the maternal or the paternal chromosome; hence, imprinted genes will be 2-fold overexpressed or not expressed. By genetic labeling of UPD, we determined cellular phenotypes and transcriptional responses to deregulated imprinted gene expression at unprecedented single-cell resolution. We discovered an unexpected degree of cell-type specificity and a novel function of imprinting in the regulation of cortical astrocyte survival. More generally, our results suggest functional relevance of imprinted gene expression in glial astrocyte lineage and thus for generating cortical cell-type diversity."}],"publication_status":"published","volume":107,"issue":"6","file_date_updated":"2020-12-02T09:26:46Z","publisher":"Elsevier","article_type":"original","intvolume":"       107","isi":1,"month":"09","date_created":"2020-07-23T16:03:12Z","status":"public"},{"publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"external_id":{"pmid":["32848067"]},"date_published":"2020-09-08T00:00:00Z","page":"22101-22112","acknowledgement":"We thank the staff of the macromolecular crystallography (MX) and SAXS beamlines at the European Synchrotron Radiation facility, Diamond, and Swiss Light Source for excellent support, and the Life Sciences Facility of the Institute of Science and Technology Austria for usage of the rheometer. We thank Life Sciences editors for editing assistance. EM data were\r\nrecorded at the EM Facility of the Vienna BioCenter Core Facilities (Austria). Confocal microscopy was carried out at the Advanced Instrument Research Facility, Jawaharlal Nehru University. K.D.-C.’s research was supported by the Initial Training Network MUZIC (ITN-MUZIC) (N°238423), Austrian Science Fund (FWF) Projects I525, I1593, P22276, P19060, and W1221, Laura Bassi Centre of Optimized Structural Studies (N°253275), a Wellcome Trust Collaborative Award (201543/Z/16/Z), COST Action BM1405, Vienna Science and Technology Fund (WWTF) Chemical Biology Project LS17-008, and Christian Doppler Laboratory for High-Content Structural Biology and Biotechnology. K.Z., J.L.A., C.S., E.A.G., and A.S. were supported by the University of Vienna, J.K. by a Wellcome Trust Collaborative Award and by the Centre of Optimized Structural Studies, M.P. by FWF Project I1593, E.d.A.R. ITN-MUZIC, and FWF Projects I525 and I1593, and T.C.M. and L.C. by FWF Project I 2408-B22. E.A.G. acknowledges the PhD program Structure and Interaction of Biological Macromolecules. M.B. acknowledges the University Grant Commission, India, for a senior research fellowship. A.B. acknowledges a JC Bose Fellowship from the Science Engineering Research Council. ","acknowledged_ssus":[{"_id":"LifeSc"}],"department":[{"_id":"CaBe"}],"doi":"10.1073/pnas.1917269117","language":[{"iso":"eng"}],"oa_version":"Published Version","type":"journal_article","date_updated":"2024-03-04T10:14:44Z","day":"08","article_processing_charge":"No","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"09","date_created":"2024-03-04T10:03:52Z","status":"public","intvolume":"       117","publisher":"Proceedings of the National Academy of Sciences","article_type":"original","volume":117,"issue":"36","abstract":[{"lang":"eng","text":"The actin cytoskeleton, a dynamic network of actin filaments and associated F-actin–binding proteins, is fundamentally important in eukaryotes. α-Actinins are major F-actin bundlers that are inhibited by Ca2+ in nonmuscle cells. Here we report the mechanism of Ca2+-mediated regulation of Entamoeba histolytica α-actinin-2 (EhActn2) with features expected for the common ancestor of Entamoeba and higher eukaryotic α-actinins. Crystal structures of Ca2+-free and Ca2+-bound EhActn2 reveal a calmodulin-like domain (CaMD) uniquely inserted within the rod domain. Integrative studies reveal an exceptionally high affinity of the EhActn2 CaMD for Ca2+, binding of which can only be regulated in the presence of physiological concentrations of Mg2+. Ca2+ binding triggers an increase in protein multidomain rigidity, reducing conformational flexibility of F-actin–binding domains via interdomain cross-talk and consequently inhibiting F-actin bundling. In vivo studies uncover that EhActn2 plays an important role in phagocytic cup formation and might constitute a new drug target for amoebic dysentery."}],"publication_status":"published","pmid":1,"publication":"Proceedings of the National Academy of Sciences","title":"Calcium modulates the domain flexibility and function of an α-actinin similar to the ancestral α-actinin","_id":"15061","oa":1,"year":"2020","citation":{"apa":"Pinotsis, N., Zielinska, K., Babuta, M., Arolas, J. L., Kostan, J., Khan, M. B., … Djinovic-Carugo, K. (2020). Calcium modulates the domain flexibility and function of an α-actinin similar to the ancestral α-actinin. <i>Proceedings of the National Academy of Sciences</i>. Proceedings of the National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.1917269117\">https://doi.org/10.1073/pnas.1917269117</a>","mla":"Pinotsis, Nikos, et al. “Calcium Modulates the Domain Flexibility and Function of an α-Actinin Similar to the Ancestral α-Actinin.” <i>Proceedings of the National Academy of Sciences</i>, vol. 117, no. 36, Proceedings of the National Academy of Sciences, 2020, pp. 22101–12, doi:<a href=\"https://doi.org/10.1073/pnas.1917269117\">10.1073/pnas.1917269117</a>.","ama":"Pinotsis N, Zielinska K, Babuta M, et al. Calcium modulates the domain flexibility and function of an α-actinin similar to the ancestral α-actinin. <i>Proceedings of the National Academy of Sciences</i>. 2020;117(36):22101-22112. doi:<a href=\"https://doi.org/10.1073/pnas.1917269117\">10.1073/pnas.1917269117</a>","ieee":"N. Pinotsis <i>et al.</i>, “Calcium modulates the domain flexibility and function of an α-actinin similar to the ancestral α-actinin,” <i>Proceedings of the National Academy of Sciences</i>, vol. 117, no. 36. Proceedings of the National Academy of Sciences, pp. 22101–22112, 2020.","ista":"Pinotsis N, Zielinska K, Babuta M, Arolas JL, Kostan J, Khan MB, Schreiner C, Testa Salmazo AP, Ciccarelli L, Puchinger M, Gkougkoulia EA, Ribeiro E de A, Marlovits TC, Bhattacharya A, Djinovic-Carugo K. 2020. Calcium modulates the domain flexibility and function of an α-actinin similar to the ancestral α-actinin. Proceedings of the National Academy of Sciences. 117(36), 22101–22112.","chicago":"Pinotsis, Nikos, Karolina Zielinska, Mrigya Babuta, Joan L. Arolas, Julius Kostan, Muhammad Bashir Khan, Claudia Schreiner, et al. “Calcium Modulates the Domain Flexibility and Function of an α-Actinin Similar to the Ancestral α-Actinin.” <i>Proceedings of the National Academy of Sciences</i>. Proceedings of the National Academy of Sciences, 2020. <a href=\"https://doi.org/10.1073/pnas.1917269117\">https://doi.org/10.1073/pnas.1917269117</a>.","short":"N. Pinotsis, K. Zielinska, M. Babuta, J.L. Arolas, J. Kostan, M.B. Khan, C. Schreiner, A.P. Testa Salmazo, L. Ciccarelli, M. Puchinger, E.A. Gkougkoulia, E. de A. Ribeiro, T.C. Marlovits, A. Bhattacharya, K. Djinovic-Carugo, Proceedings of the National Academy of Sciences 117 (2020) 22101–22112."},"main_file_link":[{"url":"https://doi.org/10.1073/pnas.191726911","open_access":"1"}],"quality_controlled":"1","author":[{"last_name":"Pinotsis","first_name":"Nikos","full_name":"Pinotsis, Nikos"},{"first_name":"Karolina","last_name":"Zielinska","full_name":"Zielinska, Karolina"},{"full_name":"Babuta, Mrigya","last_name":"Babuta","first_name":"Mrigya"},{"first_name":"Joan L.","last_name":"Arolas","full_name":"Arolas, Joan L."},{"first_name":"Julius","last_name":"Kostan","full_name":"Kostan, Julius"},{"first_name":"Muhammad Bashir","last_name":"Khan","full_name":"Khan, Muhammad Bashir"},{"last_name":"Schreiner","first_name":"Claudia","full_name":"Schreiner, Claudia"},{"full_name":"Testa Salmazo, Anita P","id":"41F1F098-F248-11E8-B48F-1D18A9856A87","last_name":"Testa Salmazo","first_name":"Anita P"},{"last_name":"Ciccarelli","first_name":"Luciano","full_name":"Ciccarelli, Luciano"},{"full_name":"Puchinger, Martin","first_name":"Martin","last_name":"Puchinger"},{"full_name":"Gkougkoulia, Eirini A.","last_name":"Gkougkoulia","first_name":"Eirini A."},{"last_name":"Ribeiro","first_name":"Euripedes de Almeida","full_name":"Ribeiro, Euripedes de Almeida"},{"last_name":"Marlovits","first_name":"Thomas C.","full_name":"Marlovits, Thomas C."},{"last_name":"Bhattacharya","first_name":"Alok","full_name":"Bhattacharya, Alok"},{"full_name":"Djinovic-Carugo, Kristina","last_name":"Djinovic-Carugo","first_name":"Kristina"}]},{"scopus_import":"1","publication_identifier":{"issn":["2405-4712"]},"page":"423-433.e1-e3","external_id":{"isi":["000499495400003"]},"file":[{"creator":"dernst","content_type":"application/pdf","file_size":4238460,"date_created":"2019-11-15T10:57:42Z","relation":"main_file","access_level":"open_access","checksum":"7a11d6c2f9523d65b049512d61733178","file_name":"2019_CellSystems_Lukacisin.pdf","file_id":"7027","date_updated":"2020-07-14T12:47:48Z"}],"date_published":"2019-11-27T00:00:00Z","department":[{"_id":"ToBo"}],"has_accepted_license":"1","language":[{"iso":"eng"}],"doi":"10.1016/j.cels.2019.10.004","acknowledged_ssus":[{"_id":"LifeSc"}],"article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","day":"27","oa_version":"Published Version","type":"journal_article","date_updated":"2023-08-30T07:24:58Z","isi":1,"intvolume":"         9","status":"public","month":"11","date_created":"2019-11-15T10:51:42Z","volume":9,"issue":"5","publisher":"Cell Press","article_type":"original","file_date_updated":"2020-07-14T12:47:48Z","_id":"7026","ddc":["570"],"oa":1,"publication":"Cell Systems","title":"Emergent gene expression responses to drug combinations predict higher-order drug interactions","abstract":[{"lang":"eng","text":"Effective design of combination therapies requires understanding the changes in cell physiology that result from drug interactions. Here, we show that the genome-wide transcriptional response to combinations of two drugs, measured at a rigorously controlled growth rate, can predict higher-order antagonism with a third drug in Saccharomyces cerevisiae. Using isogrowth profiling, over 90% of the variation in cellular response can be decomposed into three principal components (PCs) that have clear biological interpretations. We demonstrate that the third PC captures emergent transcriptional programs that are dependent on both drugs and can predict antagonism with a third drug targeting the emergent pathway. We further show that emergent gene expression patterns are most pronounced at a drug ratio where the drug interaction is strongest, providing a guideline for future measurements. Our results provide a readily applicable recipe for uncovering emergent responses in other systems and for higher-order drug combinations. A record of this paper’s transparent peer review process is included in the Supplemental Information."}],"publication_status":"published","project":[{"call_identifier":"FWF","_id":"25E9AF9E-B435-11E9-9278-68D0E5697425","grant_number":"P27201-B22","name":"Revealing the mechanisms underlying drug interactions"},{"grant_number":"RGP0042/2013","name":"Revealing the fundamental limits of cell growth","_id":"25EB3A80-B435-11E9-9278-68D0E5697425"}],"quality_controlled":"1","author":[{"first_name":"Martin","last_name":"Lukacisin","id":"298FFE8C-F248-11E8-B48F-1D18A9856A87","full_name":"Lukacisin, Martin","orcid":"0000-0001-6549-4177"},{"first_name":"Tobias","last_name":"Bollenbach","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","full_name":"Bollenbach, Tobias","orcid":"0000-0003-4398-476X"}],"citation":{"ieee":"M. Lukacisin and M. T. Bollenbach, “Emergent gene expression responses to drug combinations predict higher-order drug interactions,” <i>Cell Systems</i>, vol. 9, no. 5. Cell Press, pp. 423-433.e1-e3, 2019.","ama":"Lukacisin M, Bollenbach MT. Emergent gene expression responses to drug combinations predict higher-order drug interactions. <i>Cell Systems</i>. 2019;9(5):423-433.e1-e3. doi:<a href=\"https://doi.org/10.1016/j.cels.2019.10.004\">10.1016/j.cels.2019.10.004</a>","ista":"Lukacisin M, Bollenbach MT. 2019. Emergent gene expression responses to drug combinations predict higher-order drug interactions. Cell Systems. 9(5), 423-433.e1-e3.","chicago":"Lukacisin, Martin, and Mark Tobias Bollenbach. “Emergent Gene Expression Responses to Drug Combinations Predict Higher-Order Drug Interactions.” <i>Cell Systems</i>. Cell Press, 2019. <a href=\"https://doi.org/10.1016/j.cels.2019.10.004\">https://doi.org/10.1016/j.cels.2019.10.004</a>.","short":"M. Lukacisin, M.T. Bollenbach, Cell Systems 9 (2019) 423-433.e1-e3.","apa":"Lukacisin, M., &#38; Bollenbach, M. T. (2019). Emergent gene expression responses to drug combinations predict higher-order drug interactions. <i>Cell Systems</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.cels.2019.10.004\">https://doi.org/10.1016/j.cels.2019.10.004</a>","mla":"Lukacisin, Martin, and Mark Tobias Bollenbach. “Emergent Gene Expression Responses to Drug Combinations Predict Higher-Order Drug Interactions.” <i>Cell Systems</i>, vol. 9, no. 5, Cell Press, 2019, pp. 423-433.e1-e3, doi:<a href=\"https://doi.org/10.1016/j.cels.2019.10.004\">10.1016/j.cels.2019.10.004</a>."},"year":"2019","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"}},{"file":[{"relation":"source_file","date_created":"2019-12-12T09:32:36Z","creator":"mvasilev","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_size":20454014,"file_id":"7175","date_updated":"2020-07-14T12:47:51Z","file_name":"Thesis_Mina_final_upload_7.docx","checksum":"ef981c1a3b1d9da0edcbedcff4970d37","access_level":"closed"},{"file_id":"7176","date_updated":"2020-07-14T12:47:51Z","checksum":"3882c4585e46c9cfb486e4225cad54ab","file_name":"Thesis_Mina_final_upload_7.pdf","access_level":"open_access","relation":"main_file","date_created":"2019-12-12T09:33:10Z","file_size":11565025,"content_type":"application/pdf","creator":"mvasilev"}],"date_published":"2019-12-12T00:00:00Z","page":"192","alternative_title":["ISTA Thesis"],"publication_identifier":{"eissn":["2663-337X"]},"oa_version":"Published Version","type":"dissertation","date_updated":"2025-05-07T11:12:29Z","supervisor":[{"id":"4159519E-F248-11E8-B48F-1D18A9856A87","full_name":"Friml, Jiří","orcid":"0000-0002-8302-7596","first_name":"Jiří","last_name":"Friml"}],"day":"12","article_processing_charge":"No","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"}],"has_accepted_license":"1","department":[{"_id":"JiFr"}],"language":[{"iso":"eng"}],"doi":"10.15479/AT:ISTA:7172","file_date_updated":"2020-07-14T12:47:51Z","publisher":"Institute of Science and Technology Austria","month":"12","date_created":"2019-12-11T21:24:39Z","status":"public","degree_awarded":"PhD","year":"2019","citation":{"ama":"Vasileva MK. Molecular mechanisms of endomembrane trafficking in Arabidopsis thaliana. 2019. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7172\">10.15479/AT:ISTA:7172</a>","ieee":"M. K. Vasileva, “Molecular mechanisms of endomembrane trafficking in Arabidopsis thaliana,” Institute of Science and Technology Austria, 2019.","short":"M.K. Vasileva, Molecular Mechanisms of Endomembrane Trafficking in Arabidopsis Thaliana, Institute of Science and Technology Austria, 2019.","chicago":"Vasileva, Mina K. “Molecular Mechanisms of Endomembrane Trafficking in Arabidopsis Thaliana.” Institute of Science and Technology Austria, 2019. <a href=\"https://doi.org/10.15479/AT:ISTA:7172\">https://doi.org/10.15479/AT:ISTA:7172</a>.","ista":"Vasileva MK. 2019. Molecular mechanisms of endomembrane trafficking in Arabidopsis thaliana. Institute of Science and Technology Austria.","apa":"Vasileva, M. K. (2019). <i>Molecular mechanisms of endomembrane trafficking in Arabidopsis thaliana</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:7172\">https://doi.org/10.15479/AT:ISTA:7172</a>","mla":"Vasileva, Mina K. <i>Molecular Mechanisms of Endomembrane Trafficking in Arabidopsis Thaliana</i>. Institute of Science and Technology Austria, 2019, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7172\">10.15479/AT:ISTA:7172</a>."},"author":[{"id":"3407EB18-F248-11E8-B48F-1D18A9856A87","full_name":"Vasileva, Mina K","last_name":"Vasileva","first_name":"Mina K"}],"abstract":[{"text":"The development and growth of Arabidopsis thaliana is regulated by a combination of genetic programing and also by the environmental influences. An important role in these processes play the phytohormones and among them, auxin is crucial as it controls many important functions. It is transported through the whole plant body by creating local and temporal concentration maxima and minima, which have an impact on the cell status, tissue and organ identity. Auxin has the property to undergo a directional and finely regulated cell-to-cell transport, which is enabled by the transport proteins, localized on the plasma membrane. An important role in this process have the PIN auxin efflux proteins, which have an asymmetric/polar subcellular localization and determine the directionality of the auxin transport. During the last years, there were significant advances in understanding how the trafficking molecular machineries function, including studies on molecular interactions, function, subcellular localization and intracellular distribution. However, there is still a lack of detailed characterization on the steps of endocytosis, exocytosis, endocytic recycling and degradation. Due to this fact, I focused on the identification of novel trafficking factors and better characterization of the intracellular trafficking pathways. My PhD thesis consists of an introductory chapter, three experimental chapters, a chapter containing general discussion, conclusions and perspectives and also an appendix chapter with published collaborative papers.\r\nThe first chapter is separated in two different parts: I start by a general introduction to auxin biology and then I introduce the trafficking pathways in the model plant Arabidopsis thaliana. Then, I explain also the phosphorylation-signals for polar targeting and also the roles of the phytohormone strigolactone.\r\nThe second chapter includes the characterization of bar1/sacsin mutant, which was identified in a forward genetic screen for novel trafficking components in Arabidopsis thaliana, where by the implementation of an EMS-treated pPIN1::PIN1-GFP marker line and by using the established inhibitor of ARF-GEFs, Brefeldin A (BFA) as a tool to study trafficking processes, we identified a novel factor, which is mediating the adaptation of the plant cell to ARF-GEF inhibition. The mutation is in a previously uncharacterized gene, encoding a very big protein that we, based on its homologies, called SACSIN with domains suggesting roles as a molecular chaperon or as a component of the ubiquitin-proteasome system. Our physiology and imaging studies revealed that SACSIN is a crucial plant cell component of the adaptation to the ARF-GEF inhibition.\r\nThe third chapter includes six subchapters, where I focus on the role of the phytohormone strigolactone, which interferes with auxin feedback on PIN internalization. Strigolactone moderates the polar auxin transport by increasing the internalization of the PIN auxin efflux carriers, which reduces the canalization related growth responses. In addition, I also studied the role of phosphorylation in the strigolactone regulation of auxin feedback on PIN internalization. In this chapter I also present my results on the MAX2-dependence of strigolactone-mediated root growth inhibition and I also share my results on the auxin metabolomics profiling after application of GR24.\r\nIn the fourth chapter I studied the effect of two small molecules ES-9 and ES9-17, which were identified from a collection of small molecules with the property to impair the clathrin-mediated endocytosis.\r\nIn the fifth chapter, I discuss all my observations and experimental findings and suggest alternative hypothesis to interpret my results.\r\nIn the appendix there are three collaborative published projects. In the first, I participated in the characterization of the role of ES9 as a small molecule, which is inhibitor of clathrin- mediated endocytosis in different model organisms. In the second paper, I contributed to the characterization of another small molecule ES9-17, which is a non-protonophoric analog of ES9 and also impairs the clathrin-mediated endocytosis not only in plant cells, but also in mammalian HeLa cells. Last but not least, I also attach another paper, where I tried to establish the grafting method as a technique in our lab to study canalization related processes.","lang":"eng"}],"publication_status":"published","title":"Molecular mechanisms of endomembrane trafficking in Arabidopsis thaliana","_id":"7172","ddc":["570"],"oa":1,"related_material":{"record":[{"id":"6377","status":"public","relation":"part_of_dissertation"},{"relation":"part_of_dissertation","status":"public","id":"449"},{"relation":"part_of_dissertation","status":"public","id":"1346"}]}},{"publisher":"Institute of Science and Technology Austria","file_date_updated":"2020-07-14T12:47:52Z","status":"public","date_created":"2019-12-16T14:26:14Z","month":"12","degree_awarded":"PhD","year":"2019","author":[{"last_name":"Schwayer","first_name":"Cornelia","id":"3436488C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5130-2226","full_name":"Schwayer, Cornelia"}],"citation":{"chicago":"Schwayer, Cornelia. “Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation and Flow.” Institute of Science and Technology Austria, 2019. <a href=\"https://doi.org/10.15479/AT:ISTA:7186\">https://doi.org/10.15479/AT:ISTA:7186</a>.","short":"C. Schwayer, Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation and Flow, Institute of Science and Technology Austria, 2019.","ista":"Schwayer C. 2019. Mechanosensation of tight junctions depends on ZO-1 phase separation and flow. Institute of Science and Technology Austria.","ieee":"C. Schwayer, “Mechanosensation of tight junctions depends on ZO-1 phase separation and flow,” Institute of Science and Technology Austria, 2019.","ama":"Schwayer C. Mechanosensation of tight junctions depends on ZO-1 phase separation and flow. 2019. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7186\">10.15479/AT:ISTA:7186</a>","apa":"Schwayer, C. (2019). <i>Mechanosensation of tight junctions depends on ZO-1 phase separation and flow</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:7186\">https://doi.org/10.15479/AT:ISTA:7186</a>","mla":"Schwayer, Cornelia. <i>Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation and Flow</i>. Institute of Science and Technology Austria, 2019, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7186\">10.15479/AT:ISTA:7186</a>."},"publication_status":"published","abstract":[{"lang":"eng","text":"Tissue morphogenesis in developmental or physiological processes is regulated by molecular\r\nand mechanical signals. While the molecular signaling cascades are increasingly well\r\ndescribed, the mechanical signals affecting tissue shape changes have only recently been\r\nstudied in greater detail. To gain more insight into the mechanochemical and biophysical\r\nbasis of an epithelial spreading process (epiboly) in early zebrafish development, we studied\r\ncell-cell junction formation and actomyosin network dynamics at the boundary between\r\nsurface layer epithelial cells (EVL) and the yolk syncytial layer (YSL). During zebrafish epiboly,\r\nthe cell mass sitting on top of the yolk cell spreads to engulf the yolk cell by the end of\r\ngastrulation. It has been previously shown that an actomyosin ring residing within the YSL\r\npulls on the EVL tissue through a cable-constriction and a flow-friction motor, thereby\r\ndragging the tissue vegetal wards. Pulling forces are likely transmitted from the YSL\r\nactomyosin ring to EVL cells; however, the nature and formation of the junctional structure\r\nmediating this process has not been well described so far. Therefore, our main aim was to\r\ndetermine the nature, dynamics and potential function of the EVL-YSL junction during this\r\nepithelial tissue spreading. Specifically, we show that the EVL-YSL junction is a\r\nmechanosensitive structure, predominantly made of tight junction (TJ) proteins. The process\r\nof TJ mechanosensation depends on the retrograde flow of non-junctional, phase-separated\r\nZonula Occludens-1 (ZO-1) protein clusters towards the EVL-YSL boundary. Interestingly, we\r\ncould demonstrate that ZO-1 is present in a non-junctional pool on the surface of the yolk\r\ncell, and ZO-1 undergoes a phase separation process that likely renders the protein\r\nresponsive to flows. These flows are directed towards the junction and mediate proper\r\ntension-dependent recruitment of ZO-1. Upon reaching the EVL-YSL junction ZO-1 gets\r\nincorporated into the junctional pool mediated through its direct actin-binding domain.\r\nWhen the non-junctional pool and/or ZO-1 direct actin binding is absent, TJs fail in their\r\nproper mechanosensitive responses resulting in slower tissue spreading. We could further\r\ndemonstrate that depletion of ZO proteins within the YSL results in diminished actomyosin\r\nring formation. This suggests that a mechanochemical feedback loop is at work during\r\nzebrafish epiboly: ZO proteins help in proper actomyosin ring formation and actomyosin\r\ncontractility and flows positively influence ZO-1 junctional recruitment. Finally, such a\r\nmesoscale polarization process mediated through the flow of phase-separated protein\r\nclusters might have implications for other processes such as immunological synapse\r\nformation, C. elegans zygote polarization and wound healing."}],"ddc":["570"],"oa":1,"related_material":{"record":[{"id":"1096","relation":"dissertation_contains","status":"public"},{"status":"public","relation":"part_of_dissertation","id":"7001"}]},"_id":"7186","title":"Mechanosensation of tight junctions depends on ZO-1 phase separation and flow","page":"107","date_published":"2019-12-16T00:00:00Z","file":[{"access_level":"closed","checksum":"585583c1c875c5d9525703a539668a7c","file_name":"DocumentSourceFiles.zip","date_updated":"2020-07-14T12:47:52Z","file_id":"7194","file_size":19431292,"content_type":"application/zip","creator":"cschwayer","date_created":"2019-12-19T15:18:11Z","relation":"source_file"},{"access_level":"open_access","file_name":"Thesis_CS_final.pdf","checksum":"9b9b24351514948d27cec659e632e2cd","file_id":"7195","date_updated":"2020-07-14T12:47:52Z","file_size":19226428,"content_type":"application/pdf","creator":"cschwayer","date_created":"2019-12-19T15:19:21Z","relation":"main_file"}],"publication_identifier":{"issn":["2663-337X"]},"alternative_title":["ISTA Thesis"],"day":"16","supervisor":[{"orcid":"0000-0002-0912-4566","full_name":"Heisenberg, Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87","first_name":"Carl-Philipp J","last_name":"Heisenberg"}],"date_updated":"2023-09-07T12:56:42Z","type":"dissertation","oa_version":"Published Version","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","article_processing_charge":"No","doi":"10.15479/AT:ISTA:7186","language":[{"iso":"eng"}],"has_accepted_license":"1","department":[{"_id":"CaHe"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"EM-Fac"},{"_id":"SSU"}]},{"scopus_import":"1","publication_identifier":{"issn":["2041-1723"]},"file":[{"content_type":"application/pdf","creator":"dernst","file_size":8488733,"date_created":"2019-12-23T07:34:56Z","relation":"main_file","access_level":"open_access","checksum":"a1b44b427ba341383197790d0e8789fa","file_name":"2019_NatureComm_Caldas.pdf","date_updated":"2020-07-14T12:47:53Z","file_id":"7208"}],"external_id":{"isi":["000503009300001"]},"date_published":"2019-12-17T00:00:00Z","has_accepted_license":"1","department":[{"_id":"MaLo"},{"_id":"BjHo"}],"language":[{"iso":"eng"}],"doi":"10.1038/s41467-019-13702-4","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"}],"ec_funded":1,"day":"17","oa_version":"Published Version","type":"journal_article","date_updated":"2023-09-07T13:18:51Z","article_processing_charge":"No","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","status":"public","article_number":"5744","month":"12","date_created":"2019-12-20T12:22:57Z","isi":1,"intvolume":"        10","publisher":"Springer Nature","article_type":"original","file_date_updated":"2020-07-14T12:47:53Z","volume":10,"abstract":[{"lang":"eng","text":"During bacterial cell division, the tubulin-homolog FtsZ forms a ring-like structure at the center of the cell. This Z-ring not only organizes the division machinery, but treadmilling of FtsZ filaments was also found to play a key role in distributing proteins at the division site. What regulates the architecture, dynamics and stability of the Z-ring is currently unknown, but FtsZ-associated proteins are known to play an important role. Here, using an in vitro reconstitution approach, we studied how the well-conserved protein ZapA affects FtsZ treadmilling and filament organization into large-scale patterns. Using high-resolution fluorescence microscopy and quantitative image analysis, we found that ZapA cooperatively increases the spatial order of the filament network, but binds only transiently to FtsZ filaments and has no effect on filament length and treadmilling velocity. Together, our data provides a model for how FtsZ-associated proteins can increase the precision and stability of the bacterial cell division machinery in a switch-like manner."}],"publication_status":"published","project":[{"call_identifier":"H2020","_id":"2595697A-B435-11E9-9278-68D0E5697425","name":"Self-Organization of the Bacterial Cell","grant_number":"679239"},{"name":"Reconstitution of Bacterial Cell Division Using Purified Components","_id":"260D98C8-B435-11E9-9278-68D0E5697425"}],"_id":"7197","oa":1,"related_material":{"record":[{"id":"8358","relation":"dissertation_contains","status":"public"}]},"ddc":["570"],"title":"Cooperative ordering of treadmilling filaments in cytoskeletal networks of FtsZ and its crosslinker ZapA","publication":"Nature Communications","year":"2019","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"quality_controlled":"1","author":[{"orcid":"0000-0001-6730-4461","full_name":"Dos Santos Caldas, Paulo R","id":"38FCDB4C-F248-11E8-B48F-1D18A9856A87","last_name":"Dos Santos Caldas","first_name":"Paulo R"},{"id":"319AA9CE-F248-11E8-B48F-1D18A9856A87","full_name":"Lopez Pelegrin, Maria D","first_name":"Maria D","last_name":"Lopez Pelegrin"},{"full_name":"Pearce, Daniel J. G.","first_name":"Daniel J. G.","last_name":"Pearce"},{"full_name":"Budanur, Nazmi B","orcid":"0000-0003-0423-5010","id":"3EA1010E-F248-11E8-B48F-1D18A9856A87","last_name":"Budanur","first_name":"Nazmi B"},{"last_name":"Brugués","first_name":"Jan","full_name":"Brugués, Jan"},{"full_name":"Loose, Martin","orcid":"0000-0001-7309-9724","id":"462D4284-F248-11E8-B48F-1D18A9856A87","last_name":"Loose","first_name":"Martin"}],"citation":{"ieee":"P. R. Dos Santos Caldas, M. D. Lopez Pelegrin, D. J. G. Pearce, N. B. Budanur, J. Brugués, and M. Loose, “Cooperative ordering of treadmilling filaments in cytoskeletal networks of FtsZ and its crosslinker ZapA,” <i>Nature Communications</i>, vol. 10. Springer Nature, 2019.","ama":"Dos Santos Caldas PR, Lopez Pelegrin MD, Pearce DJG, Budanur NB, Brugués J, Loose M. Cooperative ordering of treadmilling filaments in cytoskeletal networks of FtsZ and its crosslinker ZapA. <i>Nature Communications</i>. 2019;10. doi:<a href=\"https://doi.org/10.1038/s41467-019-13702-4\">10.1038/s41467-019-13702-4</a>","short":"P.R. Dos Santos Caldas, M.D. Lopez Pelegrin, D.J.G. Pearce, N.B. Budanur, J. Brugués, M. Loose, Nature Communications 10 (2019).","chicago":"Dos Santos Caldas, Paulo R, Maria D Lopez Pelegrin, Daniel J. G. Pearce, Nazmi B Budanur, Jan Brugués, and Martin Loose. “Cooperative Ordering of Treadmilling Filaments in Cytoskeletal Networks of FtsZ and Its Crosslinker ZapA.” <i>Nature Communications</i>. Springer Nature, 2019. <a href=\"https://doi.org/10.1038/s41467-019-13702-4\">https://doi.org/10.1038/s41467-019-13702-4</a>.","ista":"Dos Santos Caldas PR, Lopez Pelegrin MD, Pearce DJG, Budanur NB, Brugués J, Loose M. 2019. Cooperative ordering of treadmilling filaments in cytoskeletal networks of FtsZ and its crosslinker ZapA. Nature Communications. 10, 5744.","apa":"Dos Santos Caldas, P. R., Lopez Pelegrin, M. D., Pearce, D. J. G., Budanur, N. B., Brugués, J., &#38; Loose, M. (2019). Cooperative ordering of treadmilling filaments in cytoskeletal networks of FtsZ and its crosslinker ZapA. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-019-13702-4\">https://doi.org/10.1038/s41467-019-13702-4</a>","mla":"Dos Santos Caldas, Paulo R., et al. “Cooperative Ordering of Treadmilling Filaments in Cytoskeletal Networks of FtsZ and Its Crosslinker ZapA.” <i>Nature Communications</i>, vol. 10, 5744, Springer Nature, 2019, doi:<a href=\"https://doi.org/10.1038/s41467-019-13702-4\">10.1038/s41467-019-13702-4</a>."}},{"volume":8,"publisher":"eLife Sciences Publications","file_date_updated":"2020-07-14T12:47:17Z","isi":1,"intvolume":"         8","article_number":"e42093","status":"public","date_created":"2019-02-17T22:59:22Z","month":"02","author":[{"first_name":"Daniel","last_name":"Capek","full_name":"Capek, Daniel","orcid":"0000-0001-5199-9940","id":"31C42484-F248-11E8-B48F-1D18A9856A87"},{"id":"3FE6E4E8-F248-11E8-B48F-1D18A9856A87","full_name":"Smutny, Michael","orcid":"0000-0002-5920-9090","last_name":"Smutny","first_name":"Michael"},{"full_name":"Tichy, Alexandra Madelaine","last_name":"Tichy","first_name":"Alexandra Madelaine"},{"last_name":"Morri","first_name":"Maurizio","full_name":"Morri, Maurizio","id":"4863116E-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-8023-9315","full_name":"Janovjak, Harald L","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","last_name":"Janovjak","first_name":"Harald L"},{"first_name":"Carl-Philipp J","last_name":"Heisenberg","id":"39427864-F248-11E8-B48F-1D18A9856A87","full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566"}],"quality_controlled":"1","citation":{"apa":"Capek, D., Smutny, M., Tichy, A. M., Morri, M., Janovjak, H. L., &#38; Heisenberg, C.-P. J. (2019). Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.42093\">https://doi.org/10.7554/eLife.42093</a>","mla":"Capek, Daniel, et al. “Light-Activated Frizzled7 Reveals a Permissive Role of Non-Canonical Wnt Signaling in Mesendoderm Cell Migration.” <i>ELife</i>, vol. 8, e42093, eLife Sciences Publications, 2019, doi:<a href=\"https://doi.org/10.7554/eLife.42093\">10.7554/eLife.42093</a>.","ieee":"D. Capek, M. Smutny, A. M. Tichy, M. Morri, H. L. Janovjak, and C.-P. J. Heisenberg, “Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration,” <i>eLife</i>, vol. 8. eLife Sciences Publications, 2019.","ama":"Capek D, Smutny M, Tichy AM, Morri M, Janovjak HL, Heisenberg C-PJ. Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration. <i>eLife</i>. 2019;8. doi:<a href=\"https://doi.org/10.7554/eLife.42093\">10.7554/eLife.42093</a>","ista":"Capek D, Smutny M, Tichy AM, Morri M, Janovjak HL, Heisenberg C-PJ. 2019. Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration. eLife. 8, e42093.","short":"D. Capek, M. Smutny, A.M. Tichy, M. Morri, H.L. Janovjak, C.-P.J. Heisenberg, ELife 8 (2019).","chicago":"Capek, Daniel, Michael Smutny, Alexandra Madelaine Tichy, Maurizio Morri, Harald L Janovjak, and Carl-Philipp J Heisenberg. “Light-Activated Frizzled7 Reveals a Permissive Role of Non-Canonical Wnt Signaling in Mesendoderm Cell Migration.” <i>ELife</i>. eLife Sciences Publications, 2019. <a href=\"https://doi.org/10.7554/eLife.42093\">https://doi.org/10.7554/eLife.42093</a>."},"year":"2019","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"ddc":["570"],"oa":1,"_id":"6025","publication":"eLife","title":"Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration","publication_status":"published","abstract":[{"text":"Non-canonical Wnt signaling plays a central role for coordinated cell polarization and directed migration in metazoan development. While spatiotemporally restricted activation of non-canonical Wnt-signaling drives cell polarization in epithelial tissues, it remains unclear whether such instructive activity is also critical for directed mesenchymal cell migration. Here, we developed a light-activated version of the non-canonical Wnt receptor Frizzled 7 (Fz7) to analyze how restricted activation of non-canonical Wnt signaling affects directed anterior axial mesendoderm (prechordal plate, ppl) cell migration within the zebrafish gastrula. We found that Fz7 signaling is required for ppl cell protrusion formation and migration and that spatiotemporally restricted ectopic activation is capable of redirecting their migration. Finally, we show that uniform activation of Fz7 signaling in ppl cells fully rescues defective directed cell migration in fz7 mutant embryos. Together, our findings reveal that in contrast to the situation in epithelial cells, non-canonical Wnt signaling functions permissively rather than instructively in directed mesenchymal cell migration during gastrulation.","lang":"eng"}],"project":[{"name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","grant_number":"742573","call_identifier":"H2020","_id":"260F1432-B435-11E9-9278-68D0E5697425"}],"date_published":"2019-02-06T00:00:00Z","file":[{"file_id":"6041","date_updated":"2020-07-14T12:47:17Z","access_level":"open_access","file_name":"2019_elife_Capek.pdf","checksum":"6cb4ca6d4aa96f6f187a5983aa3e660a","date_created":"2019-02-18T15:17:21Z","relation":"main_file","file_size":5500707,"content_type":"application/pdf","creator":"dernst"}],"external_id":{"isi":["000458025300001"]},"scopus_import":"1","article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","day":"06","date_updated":"2023-08-24T14:46:01Z","type":"journal_article","oa_version":"Published Version","language":[{"iso":"eng"}],"doi":"10.7554/eLife.42093","department":[{"_id":"CaHe"},{"_id":"HaJa"}],"has_accepted_license":"1","ec_funded":1,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}]},{"issue":"6","volume":176,"article_type":"original","publisher":"Elsevier","intvolume":"       176","isi":1,"month":"03","date_created":"2019-03-10T22:59:19Z","status":"public","citation":{"mla":"Xia, Peng, et al. “Lateral Inhibition in Cell Specification Mediated by Mechanical Signals Modulating TAZ Activity.” <i>Cell</i>, vol. 176, no. 6, Elsevier, 2019, p. 1379–1392.e14, doi:<a href=\"https://doi.org/10.1016/j.cell.2019.01.019\">10.1016/j.cell.2019.01.019</a>.","apa":"Xia, P., Gütl, D. J., Zheden, V., &#38; Heisenberg, C.-P. J. (2019). Lateral inhibition in cell specification mediated by mechanical signals modulating TAZ activity. <i>Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cell.2019.01.019\">https://doi.org/10.1016/j.cell.2019.01.019</a>","ama":"Xia P, Gütl DJ, Zheden V, Heisenberg C-PJ. Lateral inhibition in cell specification mediated by mechanical signals modulating TAZ activity. <i>Cell</i>. 2019;176(6):1379-1392.e14. doi:<a href=\"https://doi.org/10.1016/j.cell.2019.01.019\">10.1016/j.cell.2019.01.019</a>","ieee":"P. Xia, D. J. Gütl, V. Zheden, and C.-P. J. Heisenberg, “Lateral inhibition in cell specification mediated by mechanical signals modulating TAZ activity,” <i>Cell</i>, vol. 176, no. 6. Elsevier, p. 1379–1392.e14, 2019.","ista":"Xia P, Gütl DJ, Zheden V, Heisenberg C-PJ. 2019. Lateral inhibition in cell specification mediated by mechanical signals modulating TAZ activity. Cell. 176(6), 1379–1392.e14.","chicago":"Xia, Peng, Daniel J Gütl, Vanessa Zheden, and Carl-Philipp J Heisenberg. “Lateral Inhibition in Cell Specification Mediated by Mechanical Signals Modulating TAZ Activity.” <i>Cell</i>. Elsevier, 2019. <a href=\"https://doi.org/10.1016/j.cell.2019.01.019\">https://doi.org/10.1016/j.cell.2019.01.019</a>.","short":"P. Xia, D.J. Gütl, V. Zheden, C.-P.J. Heisenberg, Cell 176 (2019) 1379–1392.e14."},"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.cell.2019.01.019"}],"author":[{"last_name":"Xia","first_name":"Peng","id":"4AB6C7D0-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-5419-7756","full_name":"Xia, Peng"},{"first_name":"Daniel J","last_name":"Gütl","full_name":"Gütl, Daniel J","id":"381929CE-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Zheden, Vanessa","orcid":"0000-0002-9438-4783","id":"39C5A68A-F248-11E8-B48F-1D18A9856A87","last_name":"Zheden","first_name":"Vanessa"},{"id":"39427864-F248-11E8-B48F-1D18A9856A87","full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566","last_name":"Heisenberg","first_name":"Carl-Philipp J"}],"quality_controlled":"1","year":"2019","pmid":1,"publication":"Cell","title":"Lateral inhibition in cell specification mediated by mechanical signals modulating TAZ activity","_id":"6087","oa":1,"related_material":{"link":[{"relation":"press_release","url":"https://ist.ac.at/en/news/in-zebrafish-eggs-most-rapidly-growing-cell-inhibits-its-neighbours-through-mechanical-signals/","description":"News on IST Homepage"}]},"project":[{"name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","grant_number":"742573","call_identifier":"H2020","_id":"260F1432-B435-11E9-9278-68D0E5697425"}],"abstract":[{"text":"Cell fate specification by lateral inhibition typically involves contact signaling through the Delta-Notch signaling pathway. However, whether this is the only signaling mode mediating lateral inhibition remains unclear. Here we show that in zebrafish oogenesis, a group of cells within the granulosa cell layer at the oocyte animal pole acquire elevated levels of the transcriptional coactivator TAZ in their nuclei. One of these cells, the future micropyle precursor cell (MPC), accumulates increasingly high levels of nuclear TAZ and grows faster than its surrounding cells, mechanically compressing those cells, which ultimately lose TAZ from their nuclei. Strikingly, relieving neighbor-cell compression by MPC ablation or aspiration restores nuclear TAZ accumulation in neighboring cells, eventually leading to MPC re-specification from these cells. Conversely, MPC specification is defective in taz−/− follicles. These findings uncover a novel mode of lateral inhibition in cell fate specification based on mechanical signals controlling TAZ activity.","lang":"eng"}],"publication_status":"published","external_id":{"isi":["000460509600013"],"pmid":["30773315"]},"date_published":"2019-03-07T00:00:00Z","page":"1379-1392.e14","scopus_import":"1","article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa_version":"Published Version","date_updated":"2023-08-25T08:02:23Z","type":"journal_article","day":"07","acknowledged_ssus":[{"_id":"Bio"},{"_id":"EM-Fac"},{"_id":"LifeSc"}],"ec_funded":1,"department":[{"_id":"CaHe"},{"_id":"EM-Fac"}],"language":[{"iso":"eng"}],"doi":"10.1016/j.cell.2019.01.019","acknowledgement":"We thank Roland Dosch, Makoto Furutani-Seiki, Brian Link, Mary Mullins, and Masazumi Tada for providing transgenic and/or mutant zebrafish lines; Alexandra Schauer, Shayan Shami-Pour, and the rest of the Heisenberg lab for technical assistance and feedback on the manuscript; and the Bioimaging, Electron Microscopy, and Zebrafish facilities of IST Austria for continuous support. This work was supported by an ERC advanced grant ( MECSPEC to C.-P.H.)."},{"project":[{"_id":"253CDE40-B435-11E9-9278-68D0E5697425","grant_number":"24283","name":"Examination of the role of a MFS transporter in the migration of Drosophila immune cells"},{"name":"The role of Drosophila TNF alpha in immune cell invasion","grant_number":"P29638","call_identifier":"FWF","_id":"253B6E48-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FP7","_id":"2536F660-B435-11E9-9278-68D0E5697425","name":"Investigating the role of transporters in invasive migration through junctions","grant_number":"334077"},{"call_identifier":"FP7","_id":"25388084-B435-11E9-9278-68D0E5697425","grant_number":"329540","name":"Breaking barriers: Investigating the junctional and mechanobiological changes underlying the ability of Drosophila immune cells to invade an epithelium"},{"grant_number":"665385","name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"abstract":[{"lang":"eng","text":"Aberrant display of the truncated core1 O-glycan T-antigen is a common feature of human cancer cells that correlates with metastasis. Here we show that T-antigen in Drosophila melanogaster macrophages is involved in their developmentally programmed tissue invasion. Higher macrophage T-antigen levels require an atypical major facilitator superfamily (MFS) member that we named Minerva which enables macrophage dissemination and invasion. We characterize for the first time the T and Tn glycoform O-glycoproteome of the Drosophila melanogaster embryo, and determine that Minerva increases the presence of T-antigen on proteins in pathways previously linked to cancer, most strongly on the sulfhydryl oxidase Qsox1 which we show is required for macrophage tissue entry. Minerva’s vertebrate ortholog, MFSD1, rescues the minerva mutant’s migration and T-antigen glycosylation defects. We thus identify a key conserved regulator that orchestrates O-glycosylation on a protein subset to activate a program governing migration steps important for both development and cancer metastasis."}],"publication_status":"published","publication":"eLife","title":"A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion","_id":"6187","related_material":{"record":[{"id":"6530","relation":"dissertation_contains"},{"relation":"dissertation_contains","status":"public","id":"8983"},{"id":"6546","status":"public","relation":"dissertation_contains"}],"link":[{"description":"News on IST Homepage","relation":"press_release","url":"https://ist.ac.at/en/news/new-gene-potentially-involved-in-metastasis-identified/"}]},"ddc":["570"],"oa":1,"tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"year":"2019","citation":{"apa":"Valosková, K., Bicher, J., Roblek, M., Emtenani, S., György, A., Misova, M., … Siekhaus, D. E. (2019). A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.41801\">https://doi.org/10.7554/elife.41801</a>","mla":"Valosková, Katarina, et al. “A Conserved Major Facilitator Superfamily Member Orchestrates a Subset of O-Glycosylation to Aid Macrophage Tissue Invasion.” <i>ELife</i>, vol. 8, e41801, eLife Sciences Publications, 2019, doi:<a href=\"https://doi.org/10.7554/elife.41801\">10.7554/elife.41801</a>.","ama":"Valosková K, Bicher J, Roblek M, et al. A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion. <i>eLife</i>. 2019;8. doi:<a href=\"https://doi.org/10.7554/elife.41801\">10.7554/elife.41801</a>","ieee":"K. Valosková <i>et al.</i>, “A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion,” <i>eLife</i>, vol. 8. eLife Sciences Publications, 2019.","short":"K. Valosková, J. Bicher, M. Roblek, S. Emtenani, A. György, M. Misova, A. Ratheesh, P. Rodrigues, K. Shkarina, I.S.B. Larsen, S.Y. Vakhrushev, H. Clausen, D.E. Siekhaus, ELife 8 (2019).","chicago":"Valosková, Katarina, Julia Bicher, Marko Roblek, Shamsi Emtenani, Attila György, Michaela Misova, Aparna Ratheesh, et al. “A Conserved Major Facilitator Superfamily Member Orchestrates a Subset of O-Glycosylation to Aid Macrophage Tissue Invasion.” <i>ELife</i>. eLife Sciences Publications, 2019. <a href=\"https://doi.org/10.7554/elife.41801\">https://doi.org/10.7554/elife.41801</a>.","ista":"Valosková K, Bicher J, Roblek M, Emtenani S, György A, Misova M, Ratheesh A, Rodrigues P, Shkarina K, Larsen ISB, Vakhrushev SY, Clausen H, Siekhaus DE. 2019. A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion. eLife. 8, e41801."},"author":[{"id":"46F146FC-F248-11E8-B48F-1D18A9856A87","full_name":"Valosková, Katarina","last_name":"Valosková","first_name":"Katarina"},{"id":"3CCBB46E-F248-11E8-B48F-1D18A9856A87","full_name":"Biebl, Julia","first_name":"Julia","last_name":"Biebl"},{"id":"3047D808-F248-11E8-B48F-1D18A9856A87","full_name":"Roblek, Marko","orcid":"0000-0001-9588-1389","last_name":"Roblek","first_name":"Marko"},{"id":"49D32318-F248-11E8-B48F-1D18A9856A87","full_name":"Emtenani, Shamsi","orcid":"0000-0001-6981-6938","first_name":"Shamsi","last_name":"Emtenani"},{"orcid":"0000-0002-1819-198X","full_name":"György, Attila","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87","last_name":"György","first_name":"Attila"},{"first_name":"Michaela","last_name":"Misova","id":"495A3C32-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2427-6856","full_name":"Misova, Michaela"},{"full_name":"Ratheesh, Aparna","orcid":"0000-0001-7190-0776","id":"2F064CFE-F248-11E8-B48F-1D18A9856A87","first_name":"Aparna","last_name":"Ratheesh"},{"last_name":"Rodrigues","first_name":"Patricia","id":"2CE4065A-F248-11E8-B48F-1D18A9856A87","full_name":"Rodrigues, Patricia"},{"full_name":"Shkarina, Katerina","last_name":"Shkarina","first_name":"Katerina"},{"last_name":"Larsen","first_name":"Ida Signe Bohse","full_name":"Larsen, Ida Signe Bohse"},{"first_name":"Sergey Y","last_name":"Vakhrushev","full_name":"Vakhrushev, Sergey Y"},{"first_name":"Henrik","last_name":"Clausen","full_name":"Clausen, Henrik"},{"first_name":"Daria E","last_name":"Siekhaus","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8323-8353","full_name":"Siekhaus, Daria E"}],"quality_controlled":"1","month":"03","date_created":"2019-03-28T13:37:45Z","status":"public","article_number":"e41801","intvolume":"         8","isi":1,"file_date_updated":"2020-07-14T12:47:23Z","publisher":"eLife Sciences Publications","volume":8,"ec_funded":1,"acknowledged_ssus":[{"_id":"LifeSc"}],"has_accepted_license":"1","department":[{"_id":"DaSi"}],"doi":"10.7554/elife.41801","language":[{"iso":"eng"}],"oa_version":"Published Version","date_updated":"2024-03-25T23:30:15Z","type":"journal_article","day":"26","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"No","scopus_import":"1","publication_identifier":{"issn":["2050-084X"]},"file":[{"access_level":"open_access","checksum":"cc0d1a512559d52e7e7cb0e9b9854b40","file_name":"2019_eLife_Valoskova.pdf","file_id":"6188","date_updated":"2020-07-14T12:47:23Z","file_size":4496017,"creator":"dernst","content_type":"application/pdf","date_created":"2019-03-28T14:00:41Z","relation":"main_file"}],"external_id":{"isi":["000462530200001"]},"date_published":"2019-03-26T00:00:00Z"},{"date_created":"2019-05-09T19:53:00Z","month":"05","status":"public","file_date_updated":"2021-02-11T11:17:16Z","publisher":"IST Austria","publication_status":"published","abstract":[{"lang":"eng","text":"The regulation of gene expression is one of the most fundamental processes in living systems. In recent years, thanks to advances in sequencing technology and automation, it has become possible to study gene expression quantitatively, genome-wide and in high-throughput. This leads to the possibility of exploring changes in gene expression in the context of many external perturbations and their combinations, and thus of characterising the basic principles governing gene regulation. In this thesis, I present quantitative experimental approaches to studying transcriptional and protein level changes in response to combinatorial drug treatment, as well as a theoretical data-driven approach to analysing thermodynamic principles guiding transcription of protein coding genes.  \r\nIn the first part of this work, I present a novel methodological framework for quantifying gene expression changes in drug combinations, termed isogrowth profiling. External perturbations through small molecule drugs influence the growth rate of the cell, leading to wide-ranging changes in cellular physiology and gene expression. This confounds the gene expression changes specifically elicited by the particular drug. Combinatorial perturbations, owing to the increased stress they exert, influence the growth rate even more strongly and hence suffer the convolution problem to a greater extent when measuring gene expression changes. Isogrowth profiling is a way to experimentally abstract non-specific, growth rate related changes, by performing the measurement using varying ratios of two drugs at such concentrations that the overall inhibition rate is constant. Using a robotic setup for automated high-throughput re-dilution culture of Saccharomyces cerevisiae, the budding yeast, I investigate all pairwise interactions of four small molecule drugs through sequencing RNA along a growth isobole. Through principal component analysis, I demonstrate here that isogrowth profiling can uncover drug-specific as well as drug-interaction-specific gene expression changes. I show that drug-interaction-specific gene expression changes can be used for prediction of higher-order drug interactions. I propose a simplified generalised framework of isogrowth profiling, with few measurements needed for each drug pair, enabling the broad application of isogrowth profiling to high-throughput screening of inhibitors of cellular growth and beyond. Such high-throughput screenings of gene expression changes specific to pairwise drug interactions will be instrumental for predicting the higher-order interactions of the drugs.\r\n\r\nIn the second part of this work, I extend isogrowth profiling to single-cell measurements of gene expression, characterising population heterogeneity in the budding yeast in response to combinatorial drug perturbation while controlling for non-specific growth rate effects. Through flow cytometry of strains with protein products fused to green fluorescent protein, I discover multiple proteins with bi-modally distributed expression levels in the population in response to drug treatment. I characterize more closely the effect of an ionic stressor, lithium chloride, and find that it inhibits the splicing of mRNA, most strongly affecting ribosomal protein transcripts and leading to a bi-stable behaviour of a small ribosomal subunit protein Rps22B. Time-lapse microscopy of a microfluidic culture system revealed that the induced Rps22B heterogeneity leads to preferential survival of Rps22B-low cells after long starvation, but to preferential proliferation of Rps22B-high cells after short starvation. Overall, this suggests that yeast cells might use splicing of ribosomal genes for bet-hedging in fluctuating environments. I give specific examples of how further exploration of cellular heterogeneity in yeast in response to external perturbation has the potential to reveal yet-undiscovered gene regulation circuitry.\r\n\r\nIn the last part of this thesis, a re-analysis of a published sequencing dataset of nascent elongating transcripts is used to characterise the thermodynamic constraints for RNA polymerase II (RNAP) elongation. Population-level data on RNAP position throughout the transcribed genome with single nucleotide resolution are used to infer the sequence specific thermodynamic determinants of RNAP pausing and backtracking. This analysis reveals that the basepairing strength of the eight nucleotide-long RNA:DNA duplex relative to the basepairing strength of the same sequence when in DNA:DNA duplex, and the change in this quantity during RNA polymerase movement, is the key determinant of RNAP pausing. This is true for RNAP pausing while elongating, but also of RNAP pausing while backtracking and of the backtracking length. The quantitative dependence of RNAP pausing on basepairing energetics is used to infer the increase in pausing due to transcriptional mismatches, leading to a hypothesis that pervasive RNA polymerase II pausing is due to basepairing energetics, as an evolutionary cost for increased RNA polymerase II fidelity.\r\n\r\nThis work advances our understanding of the general principles governing gene expression, with the goal of making computational predictions of single-cell gene expression responses to combinatorial perturbations based on the individual perturbations possible. This ability would substantially facilitate the design of drug combination treatments and, in the long term, lead to our increased ability to more generally design targeted manipulations to any biological system. "}],"title":"Quantitative investigation of gene expression principles through combinatorial drug perturbation and theory","related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"1029"}]},"ddc":["570"],"oa":1,"_id":"6392","year":"2019","citation":{"apa":"Lukacisin, M. (2019). <i>Quantitative investigation of gene expression principles through combinatorial drug perturbation and theory</i>. IST Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:6392\">https://doi.org/10.15479/AT:ISTA:6392</a>","mla":"Lukacisin, Martin. <i>Quantitative Investigation of Gene Expression Principles through Combinatorial Drug Perturbation and Theory</i>. IST Austria, 2019, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6392\">10.15479/AT:ISTA:6392</a>.","short":"M. Lukacisin, Quantitative Investigation of Gene Expression Principles through Combinatorial Drug Perturbation and Theory, IST Austria, 2019.","chicago":"Lukacisin, Martin. “Quantitative Investigation of Gene Expression Principles through Combinatorial Drug Perturbation and Theory.” IST Austria, 2019. <a href=\"https://doi.org/10.15479/AT:ISTA:6392\">https://doi.org/10.15479/AT:ISTA:6392</a>.","ista":"Lukacisin M. 2019. Quantitative investigation of gene expression principles through combinatorial drug perturbation and theory. IST Austria.","ieee":"M. Lukacisin, “Quantitative investigation of gene expression principles through combinatorial drug perturbation and theory,” IST Austria, 2019.","ama":"Lukacisin M. Quantitative investigation of gene expression principles through combinatorial drug perturbation and theory. 2019. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6392\">10.15479/AT:ISTA:6392</a>"},"extern":"1","author":[{"id":"298FFE8C-F248-11E8-B48F-1D18A9856A87","full_name":"Lukacisin, Martin","orcid":"0000-0001-6549-4177","last_name":"Lukacisin","first_name":"Martin"}],"alternative_title":["IST Austria Thesis"],"publication_identifier":{"isbn":["978-3-99078-001-5"],"issn":["2663-337X"]},"date_published":"2019-05-09T00:00:00Z","file":[{"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","creator":"mlukacisin","file_size":43740796,"date_created":"2019-05-10T13:51:49Z","embargo_to":"open_access","relation":"hidden","access_level":"closed","file_name":"Thesis_Draft_v3.4Final.docx","checksum":"829bda074444857c7935171237bb7c0c","date_updated":"2020-07-14T12:47:29Z","file_id":"6409"},{"embargo":"2020-04-17","creator":"mlukacisin","content_type":"application/pdf","file_size":35228388,"date_created":"2019-05-10T14:13:42Z","relation":"main_file","access_level":"open_access","checksum":"56cb5e97f5f8fc41692401b53832d8e0","file_name":"Thesis_Draft_v3.4FinalA.pdf","file_id":"6410","date_updated":"2021-02-11T11:17:16Z"}],"page":"103","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"Bio"}],"doi":"10.15479/AT:ISTA:6392","language":[{"iso":"eng"}],"department":[{"_id":"ToBo"}],"has_accepted_license":"1","date_updated":"2023-09-22T09:19:41Z","type":"dissertation","oa_version":"Published Version","day":"09","supervisor":[{"id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4398-476X","full_name":"Bollenbach, Mark Tobias","first_name":"Mark Tobias","last_name":"Bollenbach"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"},{"alternative_title":["ISTA Thesis"],"publication_identifier":{"issn":["2663-337X"]},"file":[{"embargo":"2020-05-08","content_type":"application/pdf","creator":"casillas","file_size":3895187,"date_created":"2019-05-13T09:16:20Z","relation":"main_file","access_level":"open_access","checksum":"6daf2d2086111aa8fd3fbc919a3e2833","file_name":"tesisDoctoradoBC.pdf","file_id":"6438","date_updated":"2021-02-11T11:17:15Z"},{"checksum":"3d221aaff7559a7060230a1ff610594f","file_name":"tesisDoctoradoBC.zip","access_level":"closed","date_updated":"2020-07-14T12:47:30Z","file_id":"6439","file_size":7365118,"creator":"casillas","content_type":"application/zip","relation":"source_file","embargo_to":"open_access","date_created":"2019-05-13T09:16:20Z"}],"keyword":["Social Immunity","Sanitary care","Social Insects","Organisational Immunity","Colony development","Multi-target tracking"],"date_published":"2019-05-07T00:00:00Z","page":"183","ec_funded":1,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"ScienComp"},{"_id":"M-Shop"},{"_id":"LifeSc"}],"has_accepted_license":"1","department":[{"_id":"SyCr"}],"doi":"10.15479/AT:ISTA:6435","language":[{"iso":"eng"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","article_processing_charge":"No","oa_version":"Published Version","type":"dissertation","date_updated":"2023-09-07T12:57:04Z","supervisor":[{"first_name":"Sylvia M","last_name":"Cremer","id":"2F64EC8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2193-3868","full_name":"Cremer, Sylvia M"}],"day":"07","degree_awarded":"PhD","month":"05","date_created":"2019-05-13T08:58:35Z","status":"public","file_date_updated":"2021-02-11T11:17:15Z","publisher":"Institute of Science and Technology Austria","title":"Collective defenses of garden ants against a fungal pathogen","_id":"6435","related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"1999"}]},"ddc":["570","006","578","592"],"oa":1,"project":[{"_id":"2649B4DE-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"771402","name":"Epidemics in ant societies on a chip"}],"abstract":[{"text":"Social insect colonies tend to have numerous members which function together like a single organism in such harmony that the term ``super-organism'' is often used. In this analogy the reproductive caste is analogous to the primordial germ\r\ncells of a metazoan, while the sterile worker caste corresponds to somatic cells. The worker castes, like tissues, are\r\nin charge of all functions of a living being, besides reproduction. The establishment of new super-organismal units\r\n(i.e. new colonies) is accomplished by the co-dependent castes. The term oftentimes goes beyond a metaphor. We invoke it when we speak about the metabolic rate, thermoregulation, nutrient regulation and gas exchange of a social insect colony. Furthermore, we assert that the super-organism has an immune system, and benefits from ``social immunity''.\r\n\r\nSocial immunity was first summoned by evolutionary biologists to resolve the apparent discrepancy between the expected high frequency of disease outbreak amongst numerous, closely related tightly-interacting hosts, living in stable and microbially-rich environments, against the exceptionally scarce epidemic accounts in natural populations. Social\r\nimmunity comprises a multi-layer assembly of behaviours which have evolved to effectively keep the pathogenic enemies of a colony at bay. The field of social immunity has drawn interest, as it becomes increasingly urgent to stop\r\nthe collapse of pollinator species and curb the growth of invasive pests. In the past decade, several mechanisms of\r\nsocial immune responses have been dissected, but many more questions remain open.\r\n\r\nI present my work in two experimental chapters. In the first, I use invasive garden ants (*Lasius neglectus*) to study how pathogen load and its distribution among nestmates affect the grooming response of the group. Any given group of ants will carry out the same total grooming work, but will direct their grooming effort towards individuals\r\ncarrying a relatively higher spore load. Contrary to expectation, the highest risk of transmission does not stem from grooming highly contaminated ants, but instead, we suggest that the grooming response likely minimizes spore loss to the environment, reducing contamination from inadvertent pickup from the substrate.\r\n\r\nThe second is a comparative developmental approach. I follow black garden ant queens (*Lasius niger*) and their colonies from mating flight, through hibernation for a year. Colonies which grow fast from the start, have a lower chance of survival through hibernation, and those which survive grow at a lower pace later. This is true for colonies of naive\r\nand challenged queens. Early pathogen exposure of the queens changes colony dynamics in an unexpected way: colonies from exposed queens are more likely to grow slowly and recover in numbers only after they survive hibernation.\r\n\r\nIn addition to the two experimental chapters, this thesis includes a co-authored published review on organisational\r\nimmunity, where we enlist the experimental evidence and theoretical framework on which this hypothesis is built,\r\nidentify the caveats and underline how the field is ripe to overcome them. In a final chapter, I describe my part in\r\ntwo collaborative efforts, one to develop an image-based tracker, and the second to develop a classifier for ant\r\nbehaviour.","lang":"eng"}],"publication_status":"published","citation":{"apa":"Casillas Perez, B. E. (2019). <i>Collective defenses of garden ants against a fungal pathogen</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:6435\">https://doi.org/10.15479/AT:ISTA:6435</a>","mla":"Casillas Perez, Barbara E. <i>Collective Defenses of Garden Ants against a Fungal Pathogen</i>. Institute of Science and Technology Austria, 2019, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6435\">10.15479/AT:ISTA:6435</a>.","ista":"Casillas Perez BE. 2019. Collective defenses of garden ants against a fungal pathogen. Institute of Science and Technology Austria.","chicago":"Casillas Perez, Barbara E. “Collective Defenses of Garden Ants against a Fungal Pathogen.” Institute of Science and Technology Austria, 2019. <a href=\"https://doi.org/10.15479/AT:ISTA:6435\">https://doi.org/10.15479/AT:ISTA:6435</a>.","short":"B.E. Casillas Perez, Collective Defenses of Garden Ants against a Fungal Pathogen, Institute of Science and Technology Austria, 2019.","ama":"Casillas Perez BE. Collective defenses of garden ants against a fungal pathogen. 2019. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6435\">10.15479/AT:ISTA:6435</a>","ieee":"B. E. Casillas Perez, “Collective defenses of garden ants against a fungal pathogen,” Institute of Science and Technology Austria, 2019."},"author":[{"id":"351ED2AA-F248-11E8-B48F-1D18A9856A87","full_name":"Casillas Perez, Barbara E","first_name":"Barbara E","last_name":"Casillas Perez"}],"year":"2019"},{"ec_funded":1,"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"}],"doi":"10.1242/dev.175919","language":[{"iso":"eng"}],"department":[{"_id":"EvBe"}],"acknowledgement":"We thank Jiri Friml and Phillip Brewer for inspiring discussion and for help in preparing the manuscript. This research was supported by the Scientific Service Units (SSU) of IST-Austria through resources provided by the Bioimaging Facility\r\n(BIF), the Life Science Facility (LSF).\r\nThis work was supported by grants from the European Research Council (Starting Independent Research Grant ERC-2007-Stg- 207362-HCPO to E.B.). J.P. and M.S. received funds from European Regional Development Fund-Project ‘Centre for Experimental Plant Biology’ (No. CZ.02.1.01/0.0/0.0/16_019/0000738).","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"No","type":"journal_article","date_updated":"2025-05-07T11:10:55Z","oa_version":"Published Version","day":"12","publication_identifier":{"eissn":["14779129"]},"scopus_import":"1","date_published":"2019-09-12T00:00:00Z","external_id":{"isi":["000486297400011"],"pmid":["31391194"]},"title":"Root gravity response module guides differential growth determining both root bending and apical hook formation in Arabidopsis","publication":"Development","pmid":1,"oa":1,"_id":"6897","project":[{"_id":"253FCA6A-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"Hormonal cross-talk in plant organogenesis","grant_number":"207362"}],"publication_status":"published","abstract":[{"lang":"eng","text":"The apical hook is a transiently formed structure that plays a protective role when the germinating seedling penetrates through the soil towards the surface. Crucial for proper bending is the local auxin maxima, which defines the concave (inner) side of the hook curvature. As no sign of asymmetric auxin distribution has been reported in embryonic hypocotyls prior to hook formation, the question of how auxin asymmetry is established in the early phases of seedling germination remains largely unanswered. Here, we analyzed the auxin distribution and expression of PIN auxin efflux carriers from early phases of germination, and show that bending of the root in response to gravity is the crucial initial cue that governs the hypocotyl bending required for apical hook formation. Importantly, polar auxin transport machinery is established gradually after germination starts as a result of tight root-hypocotyl interaction and a proper balance between abscisic acid and gibberellins."}],"citation":{"chicago":"Zhu, Qiang, Marçal Gallemi, Jiří Pospíšil, Petra Žádníková, Miroslav Strnad, and Eva Benková. “Root Gravity Response Module Guides Differential Growth Determining Both Root Bending and Apical Hook Formation in Arabidopsis.” <i>Development</i>. The Company of Biologists, 2019. <a href=\"https://doi.org/10.1242/dev.175919\">https://doi.org/10.1242/dev.175919</a>.","short":"Q. Zhu, M. Gallemi, J. Pospíšil, P. Žádníková, M. Strnad, E. Benková, Development 146 (2019).","ista":"Zhu Q, Gallemi M, Pospíšil J, Žádníková P, Strnad M, Benková E. 2019. Root gravity response module guides differential growth determining both root bending and apical hook formation in Arabidopsis. Development. 146(17), dev175919.","ama":"Zhu Q, Gallemi M, Pospíšil J, Žádníková P, Strnad M, Benková E. Root gravity response module guides differential growth determining both root bending and apical hook formation in Arabidopsis. <i>Development</i>. 2019;146(17). doi:<a href=\"https://doi.org/10.1242/dev.175919\">10.1242/dev.175919</a>","ieee":"Q. Zhu, M. Gallemi, J. Pospíšil, P. Žádníková, M. Strnad, and E. Benková, “Root gravity response module guides differential growth determining both root bending and apical hook formation in Arabidopsis,” <i>Development</i>, vol. 146, no. 17. The Company of Biologists, 2019.","apa":"Zhu, Q., Gallemi, M., Pospíšil, J., Žádníková, P., Strnad, M., &#38; Benková, E. (2019). Root gravity response module guides differential growth determining both root bending and apical hook formation in Arabidopsis. <i>Development</i>. The Company of Biologists. <a href=\"https://doi.org/10.1242/dev.175919\">https://doi.org/10.1242/dev.175919</a>","mla":"Zhu, Qiang, et al. “Root Gravity Response Module Guides Differential Growth Determining Both Root Bending and Apical Hook Formation in Arabidopsis.” <i>Development</i>, vol. 146, no. 17, dev175919, The Company of Biologists, 2019, doi:<a href=\"https://doi.org/10.1242/dev.175919\">10.1242/dev.175919</a>."},"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1242/dev.175919"}],"quality_controlled":"1","author":[{"last_name":"Zhu","first_name":"Qiang","full_name":"Zhu, Qiang","id":"40A4B9E6-F248-11E8-B48F-1D18A9856A87"},{"id":"460C6802-F248-11E8-B48F-1D18A9856A87","full_name":"Gallemi, Marçal","orcid":"0000-0003-4675-6893","first_name":"Marçal","last_name":"Gallemi"},{"last_name":"Pospíšil","first_name":"Jiří","full_name":"Pospíšil, Jiří"},{"first_name":"Petra","last_name":"Žádníková","full_name":"Žádníková, Petra"},{"full_name":"Strnad, Miroslav","first_name":"Miroslav","last_name":"Strnad"},{"last_name":"Benková","first_name":"Eva","id":"38F4F166-F248-11E8-B48F-1D18A9856A87","full_name":"Benková, Eva","orcid":"0000-0002-8510-9739"}],"year":"2019","intvolume":"       146","isi":1,"date_created":"2019-09-22T22:00:36Z","month":"09","status":"public","article_number":"dev175919","issue":"17","volume":146,"article_type":"original","publisher":"The Company of Biologists"},{"publisher":"Genetics Society of America","file_date_updated":"2020-07-14T12:46:56Z","volume":8,"issue":"3","pubrep_id":"990","status":"public","date_created":"2018-12-11T11:47:05Z","month":"03","publist_id":"7271","isi":1,"intvolume":"         8","year":"2018","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"quality_controlled":"1","author":[{"id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1819-198X","full_name":"György, Attila","first_name":"Attila","last_name":"György"},{"full_name":"Roblek, Marko","orcid":"0000-0001-9588-1389","id":"3047D808-F248-11E8-B48F-1D18A9856A87","last_name":"Roblek","first_name":"Marko"},{"full_name":"Ratheesh, Aparna","orcid":"0000-0001-7190-0776","id":"2F064CFE-F248-11E8-B48F-1D18A9856A87","last_name":"Ratheesh","first_name":"Aparna"},{"full_name":"Valosková, Katarina","id":"46F146FC-F248-11E8-B48F-1D18A9856A87","last_name":"Valosková","first_name":"Katarina"},{"last_name":"Belyaeva","first_name":"Vera","full_name":"Belyaeva, Vera","id":"47F080FE-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Stephanie","last_name":"Wachner","id":"2A95E7B0-F248-11E8-B48F-1D18A9856A87","full_name":"Wachner, Stephanie"},{"last_name":"Matsubayashi","first_name":"Yutaka","full_name":"Matsubayashi, Yutaka"},{"first_name":"Besaiz","last_name":"Sanchez Sanchez","full_name":"Sanchez Sanchez, Besaiz"},{"last_name":"Stramer","first_name":"Brian","full_name":"Stramer, Brian"},{"first_name":"Daria E","last_name":"Siekhaus","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","full_name":"Siekhaus, Daria E","orcid":"0000-0001-8323-8353"}],"citation":{"ieee":"A. György <i>et al.</i>, “Tools allowing independent visualization and genetic manipulation of Drosophila melanogaster macrophages and surrounding tissues,” <i>G3: Genes, Genomes, Genetics</i>, vol. 8, no. 3. Genetics Society of America, pp. 845–857, 2018.","ama":"György A, Roblek M, Ratheesh A, et al. Tools allowing independent visualization and genetic manipulation of Drosophila melanogaster macrophages and surrounding tissues. <i>G3: Genes, Genomes, Genetics</i>. 2018;8(3):845-857. doi:<a href=\"https://doi.org/10.1534/g3.117.300452\">10.1534/g3.117.300452</a>","ista":"György A, Roblek M, Ratheesh A, Valosková K, Belyaeva V, Wachner S, Matsubayashi Y, Sanchez Sanchez B, Stramer B, Siekhaus DE. 2018. Tools allowing independent visualization and genetic manipulation of Drosophila melanogaster macrophages and surrounding tissues. G3: Genes, Genomes, Genetics. 8(3), 845–857.","short":"A. György, M. Roblek, A. Ratheesh, K. Valosková, V. Belyaeva, S. Wachner, Y. Matsubayashi, B. Sanchez Sanchez, B. Stramer, D.E. Siekhaus, G3: Genes, Genomes, Genetics 8 (2018) 845–857.","chicago":"György, Attila, Marko Roblek, Aparna Ratheesh, Katarina Valosková, Vera Belyaeva, Stephanie Wachner, Yutaka Matsubayashi, Besaiz Sanchez Sanchez, Brian Stramer, and Daria E Siekhaus. “Tools Allowing Independent Visualization and Genetic Manipulation of Drosophila Melanogaster Macrophages and Surrounding Tissues.” <i>G3: Genes, Genomes, Genetics</i>. Genetics Society of America, 2018. <a href=\"https://doi.org/10.1534/g3.117.300452\">https://doi.org/10.1534/g3.117.300452</a>.","mla":"György, Attila, et al. “Tools Allowing Independent Visualization and Genetic Manipulation of Drosophila Melanogaster Macrophages and Surrounding Tissues.” <i>G3: Genes, Genomes, Genetics</i>, vol. 8, no. 3, Genetics Society of America, 2018, pp. 845–57, doi:<a href=\"https://doi.org/10.1534/g3.117.300452\">10.1534/g3.117.300452</a>.","apa":"György, A., Roblek, M., Ratheesh, A., Valosková, K., Belyaeva, V., Wachner, S., … Siekhaus, D. E. (2018). Tools allowing independent visualization and genetic manipulation of Drosophila melanogaster macrophages and surrounding tissues. <i>G3: Genes, Genomes, Genetics</i>. Genetics Society of America. <a href=\"https://doi.org/10.1534/g3.117.300452\">https://doi.org/10.1534/g3.117.300452</a>"},"publication_status":"published","abstract":[{"text":"Drosophila melanogaster plasmatocytes, the phagocytic cells among hemocytes, are essential for immune responses, but also play key roles from early development to death through their interactions with other cell types. They regulate homeostasis and signaling during development, stem cell proliferation, metabolism, cancer, wound responses and aging, displaying intriguing molecular and functional conservation with vertebrate macrophages. Given the relative ease of genetics in Drosophila compared to vertebrates, tools permitting visualization and genetic manipulation of plasmatocytes and surrounding tissues independently at all stages would greatly aid in fully understanding these processes, but are lacking. Here we describe a comprehensive set of transgenic lines that allow this. These include extremely brightly fluorescing mCherry-based lines that allow GAL4-independent visualization of plasmatocyte nuclei, cytoplasm or actin cytoskeleton from embryonic Stage 8 through adulthood in both live and fixed samples even as heterozygotes, greatly facilitating screening. These lines allow live visualization and tracking of embryonic plasmatocytes, as well as larval plasmatocytes residing at the body wall or flowing with the surrounding hemolymph. With confocal imaging, interactions of plasmatocytes and inner tissues can be seen in live or fixed embryos, larvae and adults. They permit efficient GAL4-independent FACS analysis/sorting of plasmatocytes throughout life. To facilitate genetic analysis of reciprocal signaling, we have also made a plasmatocyte-expressing QF2 line that in combination with extant GAL4 drivers allows independent genetic manipulation of both plasmatocytes and surrounding tissues, and a GAL80 line that blocks GAL4 drivers from affecting plasmatocytes, both of which function from the early embryo to the adult.","lang":"eng"}],"project":[{"call_identifier":"FWF","_id":"253B6E48-B435-11E9-9278-68D0E5697425","grant_number":"P29638","name":"Drosophila TNFa´s Funktion in Immunzellen"},{"call_identifier":"FWF","_id":"253B6E48-B435-11E9-9278-68D0E5697425","name":"The role of Drosophila TNF alpha in immune cell invasion","grant_number":"P29638"},{"_id":"2637E9C0-B435-11E9-9278-68D0E5697425","grant_number":"LSC16-021 ","name":"Investigating the role of the novel major superfamily facilitator transporter family member MFSD1 in metastasis"},{"_id":"2536F660-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"334077","name":"Investigating the role of transporters in invasive migration through junctions"}],"ddc":["570"],"oa":1,"related_material":{"record":[{"relation":"research_paper","id":"6530"},{"id":"6543","relation":"research_paper"},{"status":"public","relation":"dissertation_contains","id":"11193"},{"id":"6546","status":"public","relation":"dissertation_contains"}]},"_id":"544","publication":"G3: Genes, Genomes, Genetics","title":"Tools allowing independent visualization and genetic manipulation of Drosophila melanogaster macrophages and surrounding tissues","page":"845 - 857","date_published":"2018-03-01T00:00:00Z","external_id":{"isi":["000426693300011"]},"file":[{"file_size":2251222,"creator":"system","content_type":"application/pdf","date_created":"2018-12-12T10:11:48Z","relation":"main_file","access_level":"open_access","file_name":"IST-2018-990-v1+1_2018_Gyoergy_Tools_allowing.pdf","checksum":"7d9d28b915159078a4ca7add568010e8","file_id":"4905","date_updated":"2020-07-14T12:46:56Z"}],"scopus_import":"1","day":"01","date_updated":"2024-03-25T23:30:15Z","type":"journal_article","oa_version":"Published Version","article_processing_charge":"No","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","acknowledgement":" A. Ratheesh also by Marie Curie IIF GA-2012-32950BB:DICJI, Marko Roblek by the provincial government of Lower Austria, K. Valoskova and S. Wachner by DOC Fellowships from the Austrian Academy of Sciences, ","language":[{"iso":"eng"}],"doi":"10.1534/g3.117.300452","department":[{"_id":"DaSi"}],"has_accepted_license":"1","acknowledged_ssus":[{"_id":"LifeSc"}],"ec_funded":1},{"author":[{"last_name":"Lukacisinova","first_name":"Marta","orcid":"0000-0002-2519-8004","full_name":"Lukacisinova, Marta","id":"4342E402-F248-11E8-B48F-1D18A9856A87"}],"citation":{"apa":"Lukacisinova, M. (2018). <i>Genetic determinants of antibiotic resistance evolution</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:th1072\">https://doi.org/10.15479/AT:ISTA:th1072</a>","mla":"Lukacisinova, Marta. <i>Genetic Determinants of Antibiotic Resistance Evolution</i>. Institute of Science and Technology Austria, 2018, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:th1072\">10.15479/AT:ISTA:th1072</a>.","ista":"Lukacisinova M. 2018. Genetic determinants of antibiotic resistance evolution. Institute of Science and Technology Austria.","short":"M. Lukacisinova, Genetic Determinants of Antibiotic Resistance Evolution, Institute of Science and Technology Austria, 2018.","chicago":"Lukacisinova, Marta. “Genetic Determinants of Antibiotic Resistance Evolution.” Institute of Science and Technology Austria, 2018. <a href=\"https://doi.org/10.15479/AT:ISTA:th1072\">https://doi.org/10.15479/AT:ISTA:th1072</a>.","ieee":"M. Lukacisinova, “Genetic determinants of antibiotic resistance evolution,” Institute of Science and Technology Austria, 2018.","ama":"Lukacisinova M. Genetic determinants of antibiotic resistance evolution. 2018. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:th1072\">10.15479/AT:ISTA:th1072</a>"},"year":"2018","ddc":["570","576","579"],"related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"1619"},{"relation":"part_of_dissertation","status":"public","id":"696"},{"status":"public","relation":"part_of_dissertation","id":"1027"}]},"oa":1,"_id":"6263","title":"Genetic determinants of antibiotic resistance evolution","publication_status":"published","abstract":[{"lang":"eng","text":"Antibiotic  resistance  can  emerge  spontaneously  through  genomic  mutation  and  render treatment   ineffective.   To   counteract   this process, in   addition   to   the   discovery   and description of resistance mechanisms,a deeper understanding of resistanceevolvabilityand its  determinantsis  needed. To address  this challenge,  this  thesisuncoversnew  genetic determinants   of   resistance   evolvability   using   a   customized   robotic   setup, exploressystematic   ways   in   which   resistance   evolution   is   perturbed   due   to dose-responsecharacteristics  of  drugs and  mutation  rate  differences,and  mathematically  investigates the evolutionary fate of one specific type of evolvability modifier -a stress-induced mutagenesis allele.We  find  severalgenes  which  strongly  inhibit  or  potentiate  resistance  evolution.  In  order to identify   them,   we   first developedan   automated   high-throughput   feedback-controlled protocol whichkeeps the population size and selection pressure approximately constant for hundreds  of  cultures  by  dynamically  re-diluting  the  cultures  and  adjusting  the  antibiotic concentration.  We  implementedthis  protocol  on  a  customized  liquid  handling  robot  and propagated  100  different  gene  deletion  strains  of Escherichia  coliin  triplicate  for  over  100 generations  in  tetracycline  and  in  chloramphenicol,  and  comparedtheir  adaptation  rates.We  find  a  diminishing  returns  pattern,  where  initially  sensitive  strains  adapted  more compared to less sensitive ones.  Our data uncover that deletions of certain genes which do not  affect  mutation  rate,including  efflux  pump  components,  a  chaperone  and severalstructural  and regulatory  genes  can strongly  and  reproducibly  alterresistance  evolution. Sequencing   analysis of   evolved   populations   indicates   that   epistasis   with   resistance mutations  is  the  most  likelyexplanation. This  work  could  inspire  treatment  strategies  in which  targeted  inhibitors  of  evolvability  mechanisms  will  be  given  alongside  antibiotics  to slow down resistance evolution and extend theefficacy of antibiotics.We implemented  astochasticpopulation  genetics  model, toverifyways  in  which  general properties,  namely,  dose-response  characteristics  of  drugs  and  mutation  rates,  influence evolutionary  dynamics.  In  particular,  under  the  exposure  to  antibiotics  with  shallow  dose-response  curves,bacteria  have  narrower  distributions  of  fitness  effects  of  new  mutations. We  show  that in  silicothis  also  leads  to  slower  resistance  evolution.  We see and  confirm with experiments that increased mutation rates, apart from speeding up evolution, also leadto high reproducibility of phenotypic adaptation in a context of continually strong selection pressure.Knowledge  of  these  patterns  can  aid  in  predicting  the  dynamics  of  antibiotic resistance evolutionand adapting treatment schemes accordingly.Focusing on   a   previously   described   type   of   evolvability   modifier –a   stress-induced mutagenesis  allele –we  find  conditions  under  which  it  can  persist  in  a  population  under periodic  selectionakin  to  clinical  treatment. We  set  up  a  deterministic infinite  populationcontinuous  time  model  tracking  the  frequencies  of  a  mutator  and  resistance  allele  and evaluate  various  treatment  schemes  in  how  well  they  maintain  a stress-induced mutator allele. In particular,a high diversity  of stresses  is  crucial  for  the  persistence of the  mutator allele. This leads to a general trade-off where exactly those diversifying treatment schemes which  are  likely  to  decrease  levels  of  resistance  could  lead  to  stronger  selection  of  highly evolvable genotypes.In  the  long  run,  this  work  will  lead  to  a  deeper  understanding  of  the  genetic  and  cellular mechanisms involved in antibiotic resistance evolution and could inspire new strategies for slowing down its rate. "}],"publisher":"Institute of Science and Technology Austria","file_date_updated":"2021-02-11T11:17:17Z","degree_awarded":"PhD","status":"public","date_created":"2019-04-09T13:57:15Z","month":"12","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","article_processing_charge":"No","day":"28","supervisor":[{"orcid":"0000-0003-4398-476X","full_name":"Bollenbach, Tobias","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","first_name":"Tobias","last_name":"Bollenbach"}],"date_updated":"2023-09-22T09:20:37Z","type":"dissertation","oa_version":"Published Version","doi":"10.15479/AT:ISTA:th1072","language":[{"iso":"eng"}],"department":[{"_id":"ToBo"}],"has_accepted_license":"1","acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"LifeSc"}],"page":"91","date_published":"2018-12-28T00:00:00Z","file":[{"file_id":"6264","date_updated":"2021-02-11T11:17:17Z","access_level":"open_access","file_name":"2018_Thesis_Lukacisinova.pdf","checksum":"fc60585c9eaad868ac007004ef130908","date_created":"2019-04-09T13:49:24Z","relation":"main_file","embargo":"2020-01-25","file_size":5656866,"creator":"dernst","content_type":"application/pdf"},{"file_id":"6265","date_updated":"2020-07-14T12:47:25Z","checksum":"264057ec0a92ab348cc83b41f021ba92","file_name":"2018_Thesis_Lukacisinova_source.docx","access_level":"closed","relation":"source_file","embargo_to":"open_access","date_created":"2019-04-09T13:49:23Z","file_size":5168054,"creator":"dernst","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document"}],"publication_identifier":{"issn":["2663-337X"]},"alternative_title":["ISTA Thesis"]},{"language":[{"iso":"eng"}],"doi":"10.1186/s12915-016-0294-x","department":[{"_id":"CaHe"}],"has_accepted_license":"1","acknowledged_ssus":[{"_id":"LifeSc"}],"acknowledgement":"We thank K. Lee, C. Norden, A. Webb, and the members of the Paluch lab for\r\ncomments on the manuscript. We are grateful to P. Rørth and Peter Dieterich\r\nfor discussions, S. Ares, Y. Arboleda-Estudillo and S. Schneider for technical help,\r\nM. Biro for help with programming, and the BIOTEC/MPI-CBG and IST zebrafish\r\nand imaging facilities for help and advice at various stages of this project. This work was supported by the Max Planck Society, the Medical Research Council UK (core funding to the MRC LMCB), and by grants from the Polish Ministry of Science and Higher Education (454/N-MPG/2009/0) to EKP, the Deutsche Forschungsgemeinschaft (HE 3231/6-1 and PA 1590/1-1) to CPH and EKP, a A*Star JCO career development award (12302FG010) to WY and a Damon Runyon fellowship award to ADM (DRG 2157-12). This work was also supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (FC001317), the UK Medical Research Council (FC001317), and the Wellcome Trust (FC001317) to GS.","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","day":"02","type":"journal_article","date_updated":"2021-01-12T06:49:32Z","oa_version":"Published Version","scopus_import":1,"date_published":"2016-09-02T00:00:00Z","file":[{"date_created":"2018-12-12T10:13:20Z","relation":"main_file","creator":"system","content_type":"application/pdf","file_size":1875695,"date_updated":"2020-07-14T12:44:42Z","file_id":"5002","access_level":"open_access","file_name":"IST-2016-695-v1+1_s12915-016-0294-x.pdf","checksum":"0bfa484ac69a0a560fb9a4589aeda7f6"}],"oa":1,"ddc":["572","576"],"_id":"1271","publication":"BMC Biology","title":"Steering cell migration by alternating blebs and actin-rich protrusions","publication_status":"published","abstract":[{"text":"Background: High directional persistence is often assumed to enhance the efficiency of chemotactic migration. Yet, cells in vivo usually display meandering trajectories with relatively low directional persistence, and the control and function of directional persistence during cell migration in three-dimensional environments are poorly understood. Results: Here, we use mesendoderm progenitors migrating during zebrafish gastrulation as a model system to investigate the control of directional persistence during migration in vivo. We show that progenitor cells alternate persistent run phases with tumble phases that result in cell reorientation. Runs are characterized by the formation of directed actin-rich protrusions and tumbles by enhanced blebbing. Increasing the proportion of actin-rich protrusions or blebs leads to longer or shorter run phases, respectively. Importantly, both reducing and increasing run phases result in larger spatial dispersion of the cells, indicative of reduced migration precision. A physical model quantitatively recapitulating the migratory behavior of mesendoderm progenitors indicates that the ratio of tumbling to run times, and thus the specific degree of directional persistence of migration, are critical for optimizing migration precision. Conclusions: Together, our experiments and model provide mechanistic insight into the control of migration directionality for cells moving in three-dimensional environments that combine different protrusion types, whereby the proportion of blebs to actin-rich protrusions determines the directional persistence and precision of movement by regulating the ratio of tumbling to run times.","lang":"eng"}],"project":[{"name":"Analysis of the Formation and Function of Different Cell Protusion Types During Cell Migration in Vivo","grant_number":"HE_3231/6-1","_id":"252064B8-B435-11E9-9278-68D0E5697425"}],"quality_controlled":"1","author":[{"full_name":"Diz Muñoz, Alba","last_name":"Diz Muñoz","first_name":"Alba"},{"full_name":"Romanczuk, Pawel","last_name":"Romanczuk","first_name":"Pawel"},{"full_name":"Yu, Weimiao","first_name":"Weimiao","last_name":"Yu"},{"full_name":"Bergert, Martin","last_name":"Bergert","first_name":"Martin"},{"full_name":"Ivanovitch, Kenzo","first_name":"Kenzo","last_name":"Ivanovitch"},{"first_name":"Guillame","last_name":"Salbreux","full_name":"Salbreux, Guillame"},{"full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566","id":"39427864-F248-11E8-B48F-1D18A9856A87","last_name":"Heisenberg","first_name":"Carl-Philipp J"},{"first_name":"Ewa","last_name":"Paluch","full_name":"Paluch, Ewa"}],"citation":{"short":"A. Diz Muñoz, P. Romanczuk, W. Yu, M. Bergert, K. Ivanovitch, G. Salbreux, C.-P.J. Heisenberg, E. Paluch, BMC Biology 14 (2016).","chicago":"Diz Muñoz, Alba, Pawel Romanczuk, Weimiao Yu, Martin Bergert, Kenzo Ivanovitch, Guillame Salbreux, Carl-Philipp J Heisenberg, and Ewa Paluch. “Steering Cell Migration by Alternating Blebs and Actin-Rich Protrusions.” <i>BMC Biology</i>. BioMed Central, 2016. <a href=\"https://doi.org/10.1186/s12915-016-0294-x\">https://doi.org/10.1186/s12915-016-0294-x</a>.","ista":"Diz Muñoz A, Romanczuk P, Yu W, Bergert M, Ivanovitch K, Salbreux G, Heisenberg C-PJ, Paluch E. 2016. Steering cell migration by alternating blebs and actin-rich protrusions. BMC Biology. 14(1), 74.","ieee":"A. Diz Muñoz <i>et al.</i>, “Steering cell migration by alternating blebs and actin-rich protrusions,” <i>BMC Biology</i>, vol. 14, no. 1. BioMed Central, 2016.","ama":"Diz Muñoz A, Romanczuk P, Yu W, et al. Steering cell migration by alternating blebs and actin-rich protrusions. <i>BMC Biology</i>. 2016;14(1). doi:<a href=\"https://doi.org/10.1186/s12915-016-0294-x\">10.1186/s12915-016-0294-x</a>","mla":"Diz Muñoz, Alba, et al. “Steering Cell Migration by Alternating Blebs and Actin-Rich Protrusions.” <i>BMC Biology</i>, vol. 14, no. 1, 74, BioMed Central, 2016, doi:<a href=\"https://doi.org/10.1186/s12915-016-0294-x\">10.1186/s12915-016-0294-x</a>.","apa":"Diz Muñoz, A., Romanczuk, P., Yu, W., Bergert, M., Ivanovitch, K., Salbreux, G., … Paluch, E. (2016). Steering cell migration by alternating blebs and actin-rich protrusions. <i>BMC Biology</i>. BioMed Central. <a href=\"https://doi.org/10.1186/s12915-016-0294-x\">https://doi.org/10.1186/s12915-016-0294-x</a>"},"year":"2016","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"publist_id":"6049","intvolume":"        14","status":"public","article_number":"74","date_created":"2018-12-11T11:51:04Z","month":"09","issue":"1","volume":14,"pubrep_id":"695","publisher":"BioMed Central","file_date_updated":"2020-07-14T12:44:42Z"},{"oa_version":"Published Version","date_updated":"2021-01-12T06:51:08Z","type":"journal_article","day":"01","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","acknowledgement":"This work was supported by a European Research Council Starting Inde-pendent Research grant (ERC-2007-Stg-207362-HCPO to J.D.), Research Foundation-Flanders (G033711N to A.A.), and the Austrian Science Fund (FWF01_I1774S to E.B.). P.M. is indebted to the Federation of European Biochemical Sciences for a Long-Term Fellowship. ","acknowledged_ssus":[{"_id":"LifeSc"}],"department":[{"_id":"EvBe"}],"has_accepted_license":"1","doi":"10.1101/gad.276964.115","language":[{"iso":"eng"}],"file":[{"file_id":"5883","date_updated":"2020-07-14T12:44:58Z","file_name":"2016_GeneDev_Marhavy.pdf","checksum":"ea394498ee56270e021d1028a29358a0","access_level":"open_access","relation":"main_file","date_created":"2019-01-25T09:56:11Z","file_size":2757636,"creator":"kschuh","content_type":"application/pdf"}],"external_id":{"pmid":["    26883363"]},"date_published":"2016-03-01T00:00:00Z","page":"471 - 483","scopus_import":1,"tmp":{"name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","image":"/images/cc_by_nc.png","short":"CC BY-NC (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode"},"year":"2016","citation":{"ama":"Marhavý P, Montesinos López JC, Abuzeineh A, et al. Targeted cell elimination reveals an auxin-guided biphasic mode of lateral root initiation. <i>Genes and Development</i>. 2016;30(4):471-483. doi:<a href=\"https://doi.org/10.1101/gad.276964.115\">10.1101/gad.276964.115</a>","ieee":"P. Marhavý <i>et al.</i>, “Targeted cell elimination reveals an auxin-guided biphasic mode of lateral root initiation,” <i>Genes and Development</i>, vol. 30, no. 4. Cold Spring Harbor Laboratory Press, pp. 471–483, 2016.","ista":"Marhavý P, Montesinos López JC, Abuzeineh A, Van Damme D, Vermeer J, Duclercq J, Rakusova H, Marhavá P, Friml J, Geldner N, Benková E. 2016. Targeted cell elimination reveals an auxin-guided biphasic mode of lateral root initiation. Genes and Development. 30(4), 471–483.","chicago":"Marhavý, Peter, Juan C Montesinos López, Anas Abuzeineh, Daniël Van Damme, Joop Vermeer, Jérôme Duclercq, Hana Rakusova, et al. “Targeted Cell Elimination Reveals an Auxin-Guided Biphasic Mode of Lateral Root Initiation.” <i>Genes and Development</i>. Cold Spring Harbor Laboratory Press, 2016. <a href=\"https://doi.org/10.1101/gad.276964.115\">https://doi.org/10.1101/gad.276964.115</a>.","short":"P. Marhavý, J.C. Montesinos López, A. Abuzeineh, D. Van Damme, J. Vermeer, J. Duclercq, H. Rakusova, P. Marhavá, J. Friml, N. Geldner, E. Benková, Genes and Development 30 (2016) 471–483.","apa":"Marhavý, P., Montesinos López, J. C., Abuzeineh, A., Van Damme, D., Vermeer, J., Duclercq, J., … Benková, E. (2016). Targeted cell elimination reveals an auxin-guided biphasic mode of lateral root initiation. <i>Genes and Development</i>. Cold Spring Harbor Laboratory Press. <a href=\"https://doi.org/10.1101/gad.276964.115\">https://doi.org/10.1101/gad.276964.115</a>","mla":"Marhavý, Peter, et al. “Targeted Cell Elimination Reveals an Auxin-Guided Biphasic Mode of Lateral Root Initiation.” <i>Genes and Development</i>, vol. 30, no. 4, Cold Spring Harbor Laboratory Press, 2016, pp. 471–83, doi:<a href=\"https://doi.org/10.1101/gad.276964.115\">10.1101/gad.276964.115</a>."},"author":[{"first_name":"Peter","last_name":"Marhavy","id":"3F45B078-F248-11E8-B48F-1D18A9856A87","full_name":"Marhavy, Peter","orcid":"0000-0001-5227-5741"},{"first_name":"Juan C","last_name":"Montesinos López","orcid":"0000-0001-9179-6099","full_name":"Montesinos López, Juan C","id":"310A8E3E-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Abuzeineh","first_name":"Anas","full_name":"Abuzeineh, Anas"},{"full_name":"Van Damme, Daniël","last_name":"Van Damme","first_name":"Daniël"},{"last_name":"Vermeer","first_name":"Joop","full_name":"Vermeer, Joop"},{"full_name":"Duclercq, Jérôme","last_name":"Duclercq","first_name":"Jérôme"},{"last_name":"Rakusova","first_name":"Hana","full_name":"Rakusova, Hana"},{"first_name":"Petra","last_name":"Marhavá","full_name":"Marhavá, Petra","id":"44E59624-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Jirí","last_name":"Friml","orcid":"0000-0002-8302-7596","full_name":"Friml, Jirí","id":"4159519E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Niko","last_name":"Geldner","full_name":"Geldner, Niko"},{"last_name":"Benková","first_name":"Eva","orcid":"0000-0002-8510-9739","full_name":"Benková, Eva","id":"38F4F166-F248-11E8-B48F-1D18A9856A87"}],"quality_controlled":"1","abstract":[{"lang":"eng","text":"To sustain a lifelong ability to initiate organs, plants retain pools of undifferentiated cells with a preserved prolif eration capacity. The root pericycle represents a unique tissue with conditional meristematic activity, and its tight control determines initiation of lateral organs. Here we show that the meristematic activity of the pericycle is constrained by the interaction with the adjacent endodermis. Release of these restraints by elimination of endo dermal cells by single-cell ablation triggers the pericycle to re-enter the cell cycle. We found that endodermis removal substitutes for the phytohormone auxin-dependent initiation of the pericycle meristematic activity. However, auxin is indispensable to steer the cell division plane orientation of new organ-defining divisions. We propose a dual, spatiotemporally distinct role for auxin during lateral root initiation. In the endodermis, auxin releases constraints arising from cell-to-cell interactions that compromise the pericycle meristematic activity, whereas, in the pericycle, auxin defines the orientation of the cell division plane to initiate lateral roots."}],"publication_status":"published","pmid":1,"publication":"Genes and Development","title":"Targeted cell elimination reveals an auxin-guided biphasic mode of lateral root initiation","_id":"1492","ddc":["570"],"oa":1,"file_date_updated":"2020-07-14T12:44:58Z","publisher":"Cold Spring Harbor Laboratory Press","volume":30,"issue":"4","month":"03","date_created":"2018-12-11T11:52:20Z","status":"public","intvolume":"        30","publist_id":"5691"},{"year":"2016","author":[{"first_name":"Jan","last_name":"Schwarz","id":"346C1EC6-F248-11E8-B48F-1D18A9856A87","full_name":"Schwarz, Jan"}],"citation":{"ista":"Schwarz J. 2016. Quantitative analysis of haptotactic cell migration. Institute of Science and Technology Austria.","short":"J. Schwarz, Quantitative Analysis of Haptotactic Cell Migration, Institute of Science and Technology Austria, 2016.","chicago":"Schwarz, Jan. “Quantitative Analysis of Haptotactic Cell Migration.” Institute of Science and Technology Austria, 2016.","ieee":"J. Schwarz, “Quantitative analysis of haptotactic cell migration,” Institute of Science and Technology Austria, 2016.","ama":"Schwarz J. Quantitative analysis of haptotactic cell migration. 2016.","mla":"Schwarz, Jan. <i>Quantitative Analysis of Haptotactic Cell Migration</i>. Institute of Science and Technology Austria, 2016.","apa":"Schwarz, J. (2016). <i>Quantitative analysis of haptotactic cell migration</i>. Institute of Science and Technology Austria."},"publication_status":"published","abstract":[{"text":"Directed cell migration is a hallmark feature, present in almost all multi-cellular\r\norganisms. Despite its importance, basic questions regarding force transduction\r\nor directional sensing are still heavily investigated. Directed migration of cells\r\nguided by immobilized guidance cues - haptotaxis - occurs in key-processes,\r\nsuch as embryonic development and immunity (Middleton et al., 1997; Nguyen\r\net al., 2000; Thiery, 1984; Weber et al., 2013). Immobilized guidance cues\r\ncomprise adhesive ligands, such as collagen and fibronectin (Barczyk et al.,\r\n2009), or chemokines - the main guidance cues for migratory leukocytes\r\n(Middleton et al., 1997; Weber et al., 2013). While adhesive ligands serve as\r\nattachment sites guiding cell migration (Carter, 1965), chemokines instruct\r\nhaptotactic migration by inducing adhesion to adhesive ligands and directional\r\nguidance (Rot and Andrian, 2004; Schumann et al., 2010). Quantitative analysis\r\nof the cellular response to immobilized guidance cues requires in vitro assays\r\nthat foster cell migration, offer accurate control of the immobilized cues on a\r\nsubcellular scale and in the ideal case closely reproduce in vivo conditions. The\r\nexploration of haptotactic cell migration through design and employment of such\r\nassays represents the main focus of this work.\r\nDendritic cells (DCs) are leukocytes, which after encountering danger\r\nsignals such as pathogens in peripheral organs instruct naïve T-cells and\r\nconsequently the adaptive immune response in the lymph node (Mellman and\r\nSteinman, 2001). To reach the lymph node from the periphery, DCs follow\r\nhaptotactic gradients of the chemokine CCL21 towards lymphatic vessels\r\n(Weber et al., 2013). Questions about how DCs interpret haptotactic CCL21\r\ngradients have not yet been addressed. The main reason for this is the lack of\r\nan assay that offers diverse haptotactic environments, hence allowing the study\r\nof DC migration as a response to different signals of immobilized guidance cue.\r\nIn this work, we developed an in vitro assay that enables us to\r\nquantitatively assess DC haptotaxis, by combining precisely controllable\r\nchemokine photo-patterning with physically confining migration conditions. With this tool at hand, we studied the influence of CCL21 gradient properties and\r\nconcentration on DC haptotaxis. We found that haptotactic gradient sensing\r\ndepends on the absolute CCL21 concentration in combination with the local\r\nsteepness of the gradient. Our analysis suggests that the directionality of\r\nmigrating DCs is governed by the signal-to-noise ratio of CCL21 binding to its\r\nreceptor CCR7. Moreover, the haptotactic CCL21 gradient formed in vivo\r\nprovides an optimal shape for DCs to recognize haptotactic guidance cue.\r\nBy reconstitution of the CCL21 gradient in vitro we were also able to\r\nstudy the influence of CCR7 signal termination on DC haptotaxis. To this end,\r\nwe used DCs lacking the G-protein coupled receptor kinase GRK6, which is\r\nresponsible for CCL21 induced CCR7 receptor phosphorylation and\r\ndesensitization (Zidar et al., 2009). We found that CCR7 desensitization by\r\nGRK6 is crucial for maintenance of haptotactic CCL21 gradient sensing in vitro\r\nand confirm those observations in vivo.\r\nIn the context of the organism, immobilized haptotactic guidance cues\r\noften coincide and compete with soluble chemotactic guidance cues. During\r\nwound healing, fibroblasts are exposed and influenced by adhesive cues and\r\nsoluble factors at the same time (Wu et al., 2012; Wynn, 2008). Similarly,\r\nmigrating DCs are exposed to both, soluble chemokines (CCL19 and truncated\r\nCCL21) inducing chemotactic behavior as well as the immobilized CCL21. To\r\nquantitatively assess these complex coinciding immobilized and soluble\r\nguidance cues, we implemented our chemokine photo-patterning technique in a\r\nmicrofluidic system allowing for chemotactic gradient generation. To validate\r\nthe assay, we observed DC migration in competing CCL19/CCL21\r\nenvironments.\r\nAdhesiveness guided haptotaxis has been studied intensively over the\r\nlast century. However, quantitative studies leading to conceptual models are\r\nlargely missing, again due to the lack of a precisely controllable in vitro assay. A\r\nrequirement for such an in vitro assay is that it must prevent any uncontrolled\r\ncell adhesion. This can be accomplished by stable passivation of the surface. In\r\naddition, controlled adhesion must be sustainable, quantifiable and dose\r\ndependent in order to create homogenous gradients. Therefore, we developed a novel covalent photo-patterning technique satisfying all these needs. In\r\ncombination with a sustainable poly-vinyl alcohol (PVA) surface coating we\r\nwere able to generate gradients of adhesive cue to direct cell migration. This\r\napproach allowed us to characterize the haptotactic migratory behavior of\r\nzebrafish keratocytes in vitro. Furthermore, defined patterns of adhesive cue\r\nallowed us to control for cell shape and growth on a subcellular scale.","lang":"eng"}],"ddc":["570"],"oa":1,"_id":"1129","title":"Quantitative analysis of haptotactic cell migration","publisher":"Institute of Science and Technology Austria","file_date_updated":"2021-02-22T11:43:14Z","status":"public","date_created":"2018-12-11T11:50:18Z","month":"07","publist_id":"6231","degree_awarded":"PhD","day":"01","supervisor":[{"orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","last_name":"Sixt"}],"date_updated":"2023-09-07T11:54:33Z","type":"dissertation","oa_version":"Published Version","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","article_processing_charge":"No","acknowledgement":"First, I would like to thank Michael Sixt for being a great supervisor, mentor and\r\nscientist. I highly appreciate his guidance and continued support. Furthermore, I\r\nam very grateful that he gave me the exceptional opportunity to pursue many\r\nideas of which some managed to be included in this thesis.\r\nI owe sincere thanks to the members of my PhD thesis committee, Daria\r\nSiekhaus, Daniel Legler and Harald Janovjak. Especially I would like to thank\r\nDaria for her advice and encouragement during our regular progress meetings.\r\nI also want to thank the team and fellows of the Boehringer Ingelheim Fond\r\n(BIF) PhD Fellowship for amazing and inspiring meetings and the BIF for\r\nfinancial support.\r\nImportant factors for the success of this thesis were the warm, creative\r\nand helpful atmosphere as well as the team spirit of the whole Sixt Lab.\r\nTherefore I would like to thank my current and former colleagues Frank Assen,\r\nMarkus Brown, Ingrid de Vries, Michelle Duggan, Alexander Eichner, Miroslav\r\nHons, Eva Kiermaier, Aglaja Kopf, Alexander Leithner, Christine Moussion, Jan\r\nMüller, Maria Nemethova, Jörg Renkawitz, Anne Reversat, Kari Vaahtomeri,\r\nMichele Weber and Stefan Wieser. We had an amazing time with many\r\nlegendary evenings and events. Along these lines I want to thank the in vitro\r\ncrew of the lab, Jörg, Anne and Alex, for lots of ideas and productive\r\ndiscussions. I am sure, some day we will reveal the secret of the ‘splodge’.\r\nI want to thank the members of the Heisenberg Lab for a great time and\r\nthrilling kicker matches. In this regard I especially want to thank Maurizio\r\n‘Gnocci’ Monti, Gabriel Krens, Alex Eichner, Martin Behrndt, Vanessa Barone,Philipp Schmalhorst, Michael Smutny, Daniel Capek, Anne Reversat, Eva\r\nKiermaier, Frank Assen and Jan Müller for wonderful after-lunch matches.\r\nI would not have been able to analyze the thousands of cell trajectories\r\nand probably hundreds of thousands of mouse clicks without the productive\r\ncollaboration with Veronika Bierbaum and Tobias Bollenbach. Thanks Vroni for\r\ncountless meetings, discussions and graphs and of course for proofreading and\r\nadvice for this thesis. For proofreading I also want to thank Evi, Jörg, Jack and\r\nAnne.\r\nI would like to acknowledge Matthias Mehling for a very productive\r\ncollaboration and for introducing me into the wild world of microfluidics. Jack\r\nMerrin, for countless wafers, PDMS coated coverslips and help with anything\r\nmicro-fabrication related. And Maria Nemethova for establishing the ‘click’\r\npatterning approach with me. Without her it still would be just one of the ideas…\r\nMany thanks to Ekaterina Papusheva, Robert Hauschild, Doreen Milius\r\nand Nasser Darwish from the Bioimaging Facility as well as the Preclinical and\r\nthe Life Science facilities of IST Austria for excellent technical support. At this\r\npoint I especially want to thank Robert for countless image analyses and\r\ntechnical ideas. Always interested and creative he played an essential role in all\r\nof my projects.\r\nAdditionally I want to thank Ingrid and Gabby for welcoming me warmly\r\nwhen I first started at IST, for scientific and especially mental support in all\r\nthose years, countless coffee sessions and Heurigen evenings. #BioimagingFacility #LifeScienceFacility #PreClinicalFacility","language":[{"iso":"eng"}],"has_accepted_license":"1","department":[{"_id":"MiSi"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"}],"page":"178","date_published":"2016-07-01T00:00:00Z","file":[{"access_level":"closed","checksum":"e3cd6b28f9c5cccb8891855565a2dade","file_name":"Thesis_JSchwarz_final.pdf","date_updated":"2019-08-13T10:55:35Z","file_id":"6813","file_size":32044069,"content_type":"application/pdf","creator":"dernst","date_created":"2019-08-13T10:55:35Z","relation":"main_file"},{"file_size":8396717,"creator":"dernst","content_type":"application/pdf","relation":"main_file","date_created":"2021-02-22T11:43:14Z","checksum":"c3dbe219acf87eed2f46d21d5cca00de","file_name":"2016_Thesis_JSchwarz.pdf","access_level":"open_access","success":1,"date_updated":"2021-02-22T11:43:14Z","file_id":"9181"}],"publication_identifier":{"issn":["2663-337X"]},"alternative_title":["ISTA Thesis"]},{"file":[{"file_size":1471217,"content_type":"application/pdf","creator":"system","date_created":"2018-12-12T10:18:36Z","relation":"main_file","access_level":"open_access","checksum":"c2c84bca37401435fedf76bad0ba0579","file_name":"IST-2018-1020-v1+1_Simaskova_et_al_NatCom_2015.pdf","date_updated":"2020-07-14T12:45:08Z","file_id":"5358"}],"date_published":"2015-01-01T00:00:00Z","scopus_import":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","day":"01","oa_version":"Submitted Version","type":"journal_article","date_updated":"2021-01-12T06:52:11Z","has_accepted_license":"1","department":[{"_id":"EvBe"},{"_id":"JiFr"}],"language":[{"iso":"eng"}],"doi":"10.1038/ncomms9717","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"ec_funded":1,"acknowledgement":"This work was supported by the European Research Council Starting Independent Research grant (ERC-2007-Stg-207362-HCPO to E.B., M.S., C.C.), by the Ghent University Multidisciplinary Research Partnership ‘Biotechnology for a Sustainable Economy’ no.01MRB510W, by the Research Foundation—Flanders (grant 3G033711 to J.-A.O.), by the Austrian Science Fund (FWF01_I1774S) to K.Ö.,E.B., and by the Interuniversity Attraction Poles Programme (IUAP P7/29 ‘MARS’) initiated by the Belgian Science Policy Office. I.D.C. and S.V. are post-doctoral fellows of the Research Foundation—Flanders (FWO). This research was supported by the Scientific Service Units (SSU) of IST-Austria through resources provided by the Bioimaging Facility (BIF), the Life Science Facility (LSF).","pubrep_id":"1020","volume":6,"publisher":"Nature Publishing Group","file_date_updated":"2020-07-14T12:45:08Z","publist_id":"5513","intvolume":"         6","status":"public","article_number":"8717","month":"01","date_created":"2018-12-11T11:53:12Z","quality_controlled":"1","author":[{"full_name":"Šimášková, Mária","last_name":"Šimášková","first_name":"Mária"},{"full_name":"O'Brien, José","first_name":"José","last_name":"O'Brien"},{"last_name":"Khan-Djamei","first_name":"Mamoona","id":"391B5BBC-F248-11E8-B48F-1D18A9856A87","full_name":"Khan-Djamei, Mamoona"},{"first_name":"Giel","last_name":"Van Noorden","full_name":"Van Noorden, Giel"},{"first_name":"Krisztina","last_name":"Ötvös","orcid":"0000-0002-5503-4983","full_name":"Ötvös, Krisztina","id":"29B901B0-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Anne","last_name":"Vieten","full_name":"Vieten, Anne"},{"full_name":"De Clercq, Inge","first_name":"Inge","last_name":"De Clercq"},{"first_name":"Johanna","last_name":"Van Haperen","full_name":"Van Haperen, Johanna"},{"id":"33A3C818-F248-11E8-B48F-1D18A9856A87","full_name":"Cuesta, Candela","orcid":"0000-0003-1923-2410","last_name":"Cuesta","first_name":"Candela"},{"last_name":"Hoyerová","first_name":"Klára","full_name":"Hoyerová, Klára"},{"full_name":"Vanneste, Steffen","first_name":"Steffen","last_name":"Vanneste"},{"id":"3F45B078-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5227-5741","full_name":"Marhavy, Peter","last_name":"Marhavy","first_name":"Peter"},{"first_name":"Krzysztof T","last_name":"Wabnik","id":"4DE369A4-F248-11E8-B48F-1D18A9856A87","full_name":"Wabnik, Krzysztof T","orcid":"0000-0001-7263-0560"},{"full_name":"Van Breusegem, Frank","first_name":"Frank","last_name":"Van Breusegem"},{"first_name":"Moritz","last_name":"Nowack","full_name":"Nowack, Moritz"},{"full_name":"Murphy, Angus","last_name":"Murphy","first_name":"Angus"},{"orcid":"0000-0002-8302-7596","full_name":"Friml, Jiřĺ","id":"4159519E-F248-11E8-B48F-1D18A9856A87","last_name":"Friml","first_name":"Jiřĺ"},{"last_name":"Weijers","first_name":"Dolf","full_name":"Weijers, Dolf"},{"full_name":"Beeckman, Tom","last_name":"Beeckman","first_name":"Tom"},{"id":"38F4F166-F248-11E8-B48F-1D18A9856A87","full_name":"Benková, Eva","orcid":"0000-0002-8510-9739","first_name":"Eva","last_name":"Benková"}],"citation":{"ista":"Šimášková M, O’Brien J, Khan-Djamei M, Van Noorden G, Ötvös K, Vieten A, De Clercq I, Van Haperen J, Cuesta C, Hoyerová K, Vanneste S, Marhavý P, Wabnik KT, Van Breusegem F, Nowack M, Murphy A, Friml J, Weijers D, Beeckman T, Benková E. 2015. Cytokinin response factors regulate PIN-FORMED auxin transporters. Nature Communications. 6, 8717.","chicago":"Šimášková, Mária, José O’Brien, Mamoona Khan-Djamei, Giel Van Noorden, Krisztina Ötvös, Anne Vieten, Inge De Clercq, et al. “Cytokinin Response Factors Regulate PIN-FORMED Auxin Transporters.” <i>Nature Communications</i>. Nature Publishing Group, 2015. <a href=\"https://doi.org/10.1038/ncomms9717\">https://doi.org/10.1038/ncomms9717</a>.","short":"M. Šimášková, J. O’Brien, M. Khan-Djamei, G. Van Noorden, K. Ötvös, A. Vieten, I. De Clercq, J. Van Haperen, C. Cuesta, K. Hoyerová, S. Vanneste, P. Marhavý, K.T. Wabnik, F. Van Breusegem, M. Nowack, A. Murphy, J. Friml, D. Weijers, T. Beeckman, E. Benková, Nature Communications 6 (2015).","ieee":"M. Šimášková <i>et al.</i>, “Cytokinin response factors regulate PIN-FORMED auxin transporters,” <i>Nature Communications</i>, vol. 6. Nature Publishing Group, 2015.","ama":"Šimášková M, O’Brien J, Khan-Djamei M, et al. Cytokinin response factors regulate PIN-FORMED auxin transporters. <i>Nature Communications</i>. 2015;6. doi:<a href=\"https://doi.org/10.1038/ncomms9717\">10.1038/ncomms9717</a>","apa":"Šimášková, M., O’Brien, J., Khan-Djamei, M., Van Noorden, G., Ötvös, K., Vieten, A., … Benková, E. (2015). Cytokinin response factors regulate PIN-FORMED auxin transporters. <i>Nature Communications</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/ncomms9717\">https://doi.org/10.1038/ncomms9717</a>","mla":"Šimášková, Mária, et al. “Cytokinin Response Factors Regulate PIN-FORMED Auxin Transporters.” <i>Nature Communications</i>, vol. 6, 8717, Nature Publishing Group, 2015, doi:<a href=\"https://doi.org/10.1038/ncomms9717\">10.1038/ncomms9717</a>."},"year":"2015","_id":"1640","ddc":["580"],"oa":1,"title":"Cytokinin response factors regulate PIN-FORMED auxin transporters","publication":"Nature Communications","abstract":[{"lang":"eng","text":"Auxin and cytokinin are key endogenous regulators of plant development. Although cytokinin-mediated modulation of auxin distribution is a developmentally crucial hormonal interaction, its molecular basis is largely unknown. Here we show a direct regulatory link between cytokinin signalling and the auxin transport machinery uncovering a mechanistic framework for cytokinin-auxin cross-talk. We show that the CYTOKININ RESPONSE FACTORS (CRFs), transcription factors downstream of cytokinin perception, transcriptionally control genes encoding PIN-FORMED (PIN) auxin transporters at a specific PIN CYTOKININ RESPONSE ELEMENT (PCRE) domain. Removal of this cis-regulatory element effectively uncouples PIN transcription from the CRF-mediated cytokinin regulation and attenuates plant cytokinin sensitivity. We propose that CRFs represent a missing cross-talk component that fine-tunes auxin transport capacity downstream of cytokinin signalling to control plant development."}],"publication_status":"published","project":[{"grant_number":"207362","name":"Hormonal cross-talk in plant organogenesis","call_identifier":"FP7","_id":"253FCA6A-B435-11E9-9278-68D0E5697425"},{"name":"Hormone cross-talk drives nutrient dependent plant development","grant_number":"I 1774-B16","_id":"2542D156-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}]}]