[{"oa":1,"external_id":{"pmid":["30504274"],"isi":["000455189900006"]},"isi":1,"quality_controlled":"1","project":[{"call_identifier":"FP7","name":"Investigating the role of transporters in invasive migration through junctions","_id":"2536F660-B435-11E9-9278-68D0E5697425","grant_number":"334077"}],"doi":"10.1523/JNEUROSCI.1059-18.2018","language":[{"iso":"eng"}],"month":"01","acknowledgement":"This work was supported by INSERM, CNRS, UDS, Ligue Régionale contre le Cancer, Hôpital de Strasbourg, Association pour la Recherche sur le Cancer (ARC) and Agence Nationale de la Recherche (ANR) grants. P.B.C. was funded by the ANR and by the ARSEP (Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques), and G.T. by governmental and ARC fellowships. This work was also supported by grants from the Ataxia UK (2491) and the NC3R (NC/L000199/1) awarded to M.F. The Institut de Génétique et de Biologie Moléculaire et Cellulaire was also supported by a French state fund through the ANR labex. D.E.S. was funded by Marie Curie Grant CIG 334077/IRTIM. We thank B. Altenhein, K. Brückner, M. Crozatier, L. Waltzer, M. Logan, E. Kurant, R. Reuter, E. Kurucz, J.L Dimarcq, J. Hoffmann, C. Goodman, the DHSB, and the BDSC for reagents and flies. We also thank all of the laboratory members for comments on the manuscript; C. Diebold, C. Delaporte, M. Pezze, the fly, and imaging and antibody facilities for technical assistance; and D. Dembele for help with statistics. In addition, we thank Alison Brewer for help with Luciferase assays.","year":"2019","pmid":1,"publication_status":"published","department":[{"_id":"DaSi"}],"publisher":"Society for Neuroscience","author":[{"last_name":"Trébuchet","first_name":"Guillaume","full_name":"Trébuchet, Guillaume"},{"full_name":"Cattenoz, Pierre B","last_name":"Cattenoz","first_name":"Pierre B"},{"last_name":"Zsámboki","first_name":"János","full_name":"Zsámboki, János"},{"full_name":"Mazaud, David","last_name":"Mazaud","first_name":"David"},{"id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8323-8353","first_name":"Daria E","last_name":"Siekhaus","full_name":"Siekhaus, Daria E"},{"last_name":"Fanto","first_name":"Manolis","full_name":"Fanto, Manolis"},{"first_name":"Angela","last_name":"Giangrande","full_name":"Giangrande, Angela"}],"date_created":"2018-12-11T11:44:07Z","date_updated":"2023-09-19T10:10:55Z","volume":39,"file_date_updated":"2020-10-02T09:33:28Z","publist_id":"8048","ec_funded":1,"publication":"Journal of Neuroscience","citation":{"ama":"Trébuchet G, Cattenoz PB, Zsámboki J, et al. The Repo homeodomain transcription factor suppresses hematopoiesis in Drosophila and preserves the glial fate. Journal of Neuroscience. 2019;39(2):238-255. doi:10.1523/JNEUROSCI.1059-18.2018","ieee":"G. Trébuchet et al., “The Repo homeodomain transcription factor suppresses hematopoiesis in Drosophila and preserves the glial fate,” Journal of Neuroscience, vol. 39, no. 2. Society for Neuroscience, pp. 238–255, 2019.","apa":"Trébuchet, G., Cattenoz, P. B., Zsámboki, J., Mazaud, D., Siekhaus, D. E., Fanto, M., & Giangrande, A. (2019). The Repo homeodomain transcription factor suppresses hematopoiesis in Drosophila and preserves the glial fate. Journal of Neuroscience. Society for Neuroscience. https://doi.org/10.1523/JNEUROSCI.1059-18.2018","ista":"Trébuchet G, Cattenoz PB, Zsámboki J, Mazaud D, Siekhaus DE, Fanto M, Giangrande A. 2019. The Repo homeodomain transcription factor suppresses hematopoiesis in Drosophila and preserves the glial fate. Journal of Neuroscience. 39(2), 238–255.","short":"G. Trébuchet, P.B. Cattenoz, J. Zsámboki, D. Mazaud, D.E. Siekhaus, M. Fanto, A. Giangrande, Journal of Neuroscience 39 (2019) 238–255.","mla":"Trébuchet, Guillaume, et al. “The Repo Homeodomain Transcription Factor Suppresses Hematopoiesis in Drosophila and Preserves the Glial Fate.” Journal of Neuroscience, vol. 39, no. 2, Society for Neuroscience, 2019, pp. 238–55, doi:10.1523/JNEUROSCI.1059-18.2018.","chicago":"Trébuchet, Guillaume, Pierre B Cattenoz, János Zsámboki, David Mazaud, Daria E Siekhaus, Manolis Fanto, and Angela Giangrande. “The Repo Homeodomain Transcription Factor Suppresses Hematopoiesis in Drosophila and Preserves the Glial Fate.” Journal of Neuroscience. Society for Neuroscience, 2019. https://doi.org/10.1523/JNEUROSCI.1059-18.2018."},"article_type":"original","page":"238-255","date_published":"2019-01-09T00:00:00Z","scopus_import":"1","day":"09","article_processing_charge":"No","has_accepted_license":"1","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"8","status":"public","title":"The Repo homeodomain transcription factor suppresses hematopoiesis in Drosophila and preserves the glial fate","ddc":["570"],"intvolume":" 39","oa_version":"Published Version","file":[{"date_created":"2020-10-02T09:33:28Z","date_updated":"2020-10-02T09:33:28Z","checksum":"8f6925eb4cd1e8747d8ea25929c68de6","success":1,"relation":"main_file","file_id":"8596","file_size":9455414,"content_type":"application/pdf","creator":"dernst","file_name":"2019_JournNeuroscience_Trebuchet.pdf","access_level":"open_access"}],"type":"journal_article","abstract":[{"lang":"eng","text":"Despite their different origins, Drosophila glia and hemocytes are related cell populations that provide an immune function. Drosophila hemocytes patrol the body cavity and act as macrophages outside the nervous system whereas glia originate from the neuroepithelium and provide the scavenger population of the nervous system. Drosophila glia are hence the functional orthologs of vertebrate microglia, even though the latter are cells of immune origin that subsequently move into the brain during development. Interestingly, the Drosophila immune cells within (glia) and outside the nervous system (hemocytes) require the same transcription factor Glide/Gcm for their development. This raises the issue of how do glia specifically differentiate in the nervous system and hemocytes in the procephalic mesoderm. The Repo homeodomain transcription factor and pan-glial direct target of Glide/Gcm is known to ensure glial terminal differentiation. Here we show that Repo also takes center stage in the process that discriminates between glia and hemocytes. First, Repo expression is repressed in the hemocyte anlagen by mesoderm-specific factors. Second, Repo ectopic activation in the procephalic mesoderm is sufficient to repress the expression of hemocyte-specific genes. Third, the lack of Repo triggers the expression of hemocyte markers in glia. Thus, a complex network of tissue-specific cues biases the potential of Glide/Gcm. These data allow us to revise the concept of fate determinants and help us understand the bases of cell specification. Both sexes were analyzed.SIGNIFICANCE STATEMENTDistinct cell types often require the same pioneer transcription factor, raising the issue of how does one factor trigger different fates. In Drosophila, glia and hemocytes provide a scavenger activity within and outside the nervous system, respectively. While they both require the Glide/Gcm transcription factor, glia originate from the ectoderm, hemocytes from the mesoderm. Here we show that tissue-specific factors inhibit the gliogenic potential of Glide/Gcm in the mesoderm by repressing the expression of the homeodomain protein Repo, a major glial-specific target of Glide/Gcm. Repo expression in turn inhibits the expression of hemocyte-specific genes in the nervous system. These cell-specific networks secure the establishment of the glial fate only in the nervous system and allow cell diversification."}],"issue":"2"},{"external_id":{"isi":["000470025900008"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"quality_controlled":"1","isi":1,"doi":"10.1112/jlms.12193","language":[{"iso":"eng"}],"month":"06","year":"2019","publication_status":"published","publisher":"Wiley","department":[{"_id":"TaHa"}],"author":[{"full_name":"Ganev, Iordan V","id":"447491B8-F248-11E8-B48F-1D18A9856A87","first_name":"Iordan V","last_name":"Ganev"}],"date_created":"2018-12-11T11:44:06Z","date_updated":"2023-09-19T10:13:08Z","volume":99,"file_date_updated":"2020-07-14T12:46:35Z","publist_id":"8052","license":"https://creativecommons.org/licenses/by/4.0/","publication":"Journal of the London Mathematical Society","citation":{"apa":"Ganev, I. V. (2019). The wonderful compactification for quantum groups. Journal of the London Mathematical Society. Wiley. https://doi.org/10.1112/jlms.12193","ieee":"I. V. Ganev, “The wonderful compactification for quantum groups,” Journal of the London Mathematical Society, vol. 99, no. 3. Wiley, pp. 778–806, 2019.","ista":"Ganev IV. 2019. The wonderful compactification for quantum groups. Journal of the London Mathematical Society. 99(3), 778–806.","ama":"Ganev IV. The wonderful compactification for quantum groups. Journal of the London Mathematical Society. 2019;99(3):778-806. doi:10.1112/jlms.12193","chicago":"Ganev, Iordan V. “The Wonderful Compactification for Quantum Groups.” Journal of the London Mathematical Society. Wiley, 2019. https://doi.org/10.1112/jlms.12193.","short":"I.V. Ganev, Journal of the London Mathematical Society 99 (2019) 778–806.","mla":"Ganev, Iordan V. “The Wonderful Compactification for Quantum Groups.” Journal of the London Mathematical Society, vol. 99, no. 3, Wiley, 2019, pp. 778–806, doi:10.1112/jlms.12193."},"page":"778-806","date_published":"2019-06-01T00:00:00Z","scopus_import":"1","day":"01","has_accepted_license":"1","article_processing_charge":"Yes (via OA deal)","_id":"5","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","ddc":["510"],"title":"The wonderful compactification for quantum groups","status":"public","intvolume":" 99","oa_version":"Published Version","file":[{"file_id":"7238","relation":"main_file","date_created":"2020-01-07T13:31:53Z","date_updated":"2020-07-14T12:46:35Z","checksum":"1be56239b2cd740a0e9a084f773c22f6","file_name":"2019_Wiley_Ganev.pdf","access_level":"open_access","creator":"kschuh","content_type":"application/pdf","file_size":431754}],"type":"journal_article","abstract":[{"text":"In this paper, we introduce a quantum version of the wonderful compactification of a group as a certain noncommutative projective scheme. Our approach stems from the fact that the wonderful compactification encodes the asymptotics of matrix coefficients, and from its realization as a GIT quotient of the Vinberg semigroup. In order to define the wonderful compactification for a quantum group, we adopt a generalized formalism of Proj categories in the spirit of Artin and Zhang. Key to our construction is a quantum version of the Vinberg semigroup, which we define as a q-deformation of a certain Rees algebra, compatible with a standard Poisson structure. Furthermore, we discuss quantum analogues of the stratification of the wonderful compactification by orbits for a certain group action, and provide explicit computations in the case of SL2.","lang":"eng"}],"issue":"3"},{"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"}],"alternative_title":["ISTA Thesis"],"type":"dissertation","file":[{"file_id":"7175","relation":"source_file","date_created":"2019-12-12T09:32:36Z","date_updated":"2020-07-14T12:47:51Z","checksum":"ef981c1a3b1d9da0edcbedcff4970d37","file_name":"Thesis_Mina_final_upload_7.docx","access_level":"closed","creator":"mvasilev","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_size":20454014},{"relation":"main_file","file_id":"7176","date_updated":"2020-07-14T12:47:51Z","date_created":"2019-12-12T09:33:10Z","checksum":"3882c4585e46c9cfb486e4225cad54ab","file_name":"Thesis_Mina_final_upload_7.pdf","access_level":"open_access","content_type":"application/pdf","file_size":11565025,"creator":"mvasilev"}],"oa_version":"Published Version","ddc":["570"],"title":"Molecular mechanisms of endomembrane trafficking in Arabidopsis thaliana","status":"public","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"7172","article_processing_charge":"No","has_accepted_license":"1","day":"12","date_published":"2019-12-12T00:00:00Z","page":"192","citation":{"ieee":"M. K. Vasileva, “Molecular mechanisms of endomembrane trafficking in Arabidopsis thaliana,” Institute of Science and Technology Austria, 2019.","apa":"Vasileva, M. K. (2019). Molecular mechanisms of endomembrane trafficking in Arabidopsis thaliana. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7172","ista":"Vasileva MK. 2019. Molecular mechanisms of endomembrane trafficking in Arabidopsis thaliana. Institute of Science and Technology Austria.","ama":"Vasileva MK. Molecular mechanisms of endomembrane trafficking in Arabidopsis thaliana. 2019. doi:10.15479/AT:ISTA:7172","chicago":"Vasileva, Mina K. “Molecular Mechanisms of Endomembrane Trafficking in Arabidopsis Thaliana.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:7172.","short":"M.K. Vasileva, Molecular Mechanisms of Endomembrane Trafficking in Arabidopsis Thaliana, Institute of Science and Technology Austria, 2019.","mla":"Vasileva, Mina K. Molecular Mechanisms of Endomembrane Trafficking in Arabidopsis Thaliana. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:7172."},"file_date_updated":"2020-07-14T12:47:51Z","date_created":"2019-12-11T21:24:39Z","date_updated":"2023-09-19T10:39:33Z","related_material":{"record":[{"id":"1346","relation":"part_of_dissertation","status":"public"},{"id":"6377","relation":"part_of_dissertation","status":"public"},{"id":"449","status":"public","relation":"part_of_dissertation"}]},"author":[{"id":"3407EB18-F248-11E8-B48F-1D18A9856A87","last_name":"Vasileva","first_name":"Mina K","full_name":"Vasileva, Mina K"}],"department":[{"_id":"JiFr"}],"publisher":"Institute of Science and Technology Austria","publication_status":"published","year":"2019","publication_identifier":{"eissn":["2663-337X"]},"month":"12","language":[{"iso":"eng"}],"supervisor":[{"orcid":"0000-0002-8302-7596","id":"4159519E-F248-11E8-B48F-1D18A9856A87","last_name":"Friml","first_name":"Jiří","full_name":"Friml, Jiří"}],"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"}],"degree_awarded":"PhD","doi":"10.15479/AT:ISTA:7172","oa":1},{"date_published":"2019-05-23T00:00:00Z","citation":{"ama":"Cepeda Humerez SA. Estimating information flow in single cells. 2019. doi:10.15479/AT:ISTA:6473","ista":"Cepeda Humerez SA. 2019. Estimating information flow in single cells. Institute of Science and Technology Austria.","ieee":"S. A. Cepeda Humerez, “Estimating information flow in single cells,” Institute of Science and Technology Austria, 2019.","apa":"Cepeda Humerez, S. A. (2019). Estimating information flow in single cells. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6473","mla":"Cepeda Humerez, Sarah A. Estimating Information Flow in Single Cells. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6473.","short":"S.A. Cepeda Humerez, Estimating Information Flow in Single Cells, Institute of Science and Technology Austria, 2019.","chicago":"Cepeda Humerez, Sarah A. “Estimating Information Flow in Single Cells.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6473."},"page":"135","article_processing_charge":"No","has_accepted_license":"1","day":"23","keyword":["Information estimation","Time-series","data analysis"],"file":[{"file_id":"6480","relation":"source_file","checksum":"75f9184c1346e10a5de5f9cc7338309a","date_updated":"2020-07-14T12:47:31Z","date_created":"2019-05-23T11:18:16Z","access_level":"closed","file_name":"Thesis_Cepeda.zip","creator":"scepeda","content_type":"application/zip","file_size":23937464},{"file_name":"CepedaThesis.pdf","access_level":"open_access","creator":"scepeda","file_size":16646985,"content_type":"application/pdf","file_id":"6481","relation":"main_file","date_created":"2019-05-23T11:18:13Z","date_updated":"2020-07-14T12:47:31Z","checksum":"afdc0633ddbd71d5b13550d7fb4f4454"}],"oa_version":"Published Version","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"6473","title":"Estimating information flow in single cells","ddc":["004"],"status":"public","abstract":[{"text":"Single cells are constantly interacting with their environment and each other, more importantly, the accurate perception of environmental cues is crucial for growth, survival, and reproduction. This communication between cells and their environment can be formalized in mathematical terms and be quantified as the information flow between them, as prescribed by information theory. \r\nThe recent availability of real–time dynamical patterns of signaling molecules in single cells has allowed us to identify encoding about the identity of the environment in the time–series. However, efficient estimation of the information transmitted by these signals has been a data–analysis challenge due to the high dimensionality of the trajectories and the limited number of samples. In the first part of this thesis, we develop and evaluate decoding–based estimation methods to lower bound the mutual information and derive model–based precise information estimates for biological reaction networks governed by the chemical master equation. This is followed by applying the decoding-based methods to study the intracellular representation of extracellular changes in budding yeast, by observing the transient dynamics of nuclear translocation of 10 transcription factors in response to 3 stress conditions. Additionally, we apply these estimators to previously published data on ERK and Ca2+ signaling and yeast stress response. We argue that this single cell decoding-based measure of information provides an unbiased, quantitative and interpretable measure for the fidelity of biological signaling processes. \r\nFinally, in the last section, we deal with gene regulation which is primarily controlled by transcription factors (TFs) that bind to the DNA to activate gene expression. The possibility that non-cognate TFs activate transcription diminishes the accuracy of regulation with potentially disastrous effects for the cell. This ’crosstalk’ acts as a previously unexplored source of noise in biochemical networks and puts a strong constraint on their performance. To mitigate erroneous initiation we propose an out of equilibrium scheme that implements kinetic proofreading. We show that such architectures are favored over their equilibrium counterparts for complex organisms despite introducing noise in gene expression. ","lang":"eng"}],"type":"dissertation","alternative_title":["ISTA Thesis"],"doi":"10.15479/AT:ISTA:6473","language":[{"iso":"eng"}],"degree_awarded":"PhD","supervisor":[{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","first_name":"Gašper","last_name":"Tkačik","full_name":"Tkačik, Gašper"}],"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"publication_identifier":{"issn":["2663-337X"]},"month":"05","related_material":{"record":[{"id":"1576","relation":"dissertation_contains","status":"public"},{"id":"6900","relation":"dissertation_contains","status":"public"},{"id":"281","status":"public","relation":"dissertation_contains"},{"relation":"dissertation_contains","status":"public","id":"2016"}]},"author":[{"full_name":"Cepeda Humerez, Sarah A","id":"3DEE19A4-F248-11E8-B48F-1D18A9856A87","first_name":"Sarah A","last_name":"Cepeda Humerez"}],"date_created":"2019-05-21T00:11:23Z","date_updated":"2023-09-19T15:13:26Z","year":"2019","publisher":"Institute of Science and Technology Austria","department":[{"_id":"GaTk"}],"publication_status":"published","file_date_updated":"2020-07-14T12:47:31Z"},{"has_accepted_license":"1","article_processing_charge":"No","day":"11","citation":{"ista":"Prizak R. 2019. Coevolution of transcription factors and their binding sites in sequence space. Institute of Science and Technology Austria.","apa":"Prizak, R. (2019). Coevolution of transcription factors and their binding sites in sequence space. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:th6071","ieee":"R. Prizak, “Coevolution of transcription factors and their binding sites in sequence space,” Institute of Science and Technology Austria, 2019.","ama":"Prizak R. Coevolution of transcription factors and their binding sites in sequence space. 2019. doi:10.15479/at:ista:th6071","chicago":"Prizak, Roshan. “Coevolution of Transcription Factors and Their Binding Sites in Sequence Space.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/at:ista:th6071.","mla":"Prizak, Roshan. Coevolution of Transcription Factors and Their Binding Sites in Sequence Space. Institute of Science and Technology Austria, 2019, doi:10.15479/at:ista:th6071.","short":"R. Prizak, Coevolution of Transcription Factors and Their Binding Sites in Sequence Space, Institute of Science and Technology Austria, 2019."},"page":"189","date_published":"2019-03-11T00:00:00Z","type":"dissertation","alternative_title":["ISTA Thesis"],"abstract":[{"lang":"eng","text":"Transcription factors, by binding to specific sequences on the DNA, control the precise spatio-temporal expression of genes inside a cell. However, this specificity is limited, leading to frequent incorrect binding of transcription factors that might have deleterious consequences on the cell. By constructing a biophysical model of TF-DNA binding in the context of gene regulation, I will first explore how regulatory constraints can strongly shape the distribution of a population in sequence space. Then, by directly linking this to a picture of multiple types of transcription factors performing their functions simultaneously inside the cell, I will explore the extent of regulatory crosstalk -- incorrect binding interactions between transcription factors and binding sites that lead to erroneous regulatory states -- and understand the constraints this places on the design of regulatory systems. I will then develop a generic theoretical framework to investigate the coevolution of multiple transcription factors and multiple binding sites, in the context of a gene regulatory network that performs a certain function. As a particular tractable version of this problem, I will consider the evolution of two transcription factors when they transmit upstream signals to downstream target genes. Specifically, I will describe the evolutionary steady states and the evolutionary pathways involved, along with their timescales, of a system that initially undergoes a transcription factor duplication event. To connect this important theoretical model to the prominent biological event of transcription factor duplication giving rise to paralogous families, I will then describe a bioinformatics analysis of C2H2 Zn-finger transcription factors, a major family in humans, and focus on the patterns of evolution that paralogs have undergone in their various protein domains in the recent past. "}],"_id":"6071","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","status":"public","ddc":["576"],"title":"Coevolution of transcription factors and their binding sites in sequence space","oa_version":"Published Version","file":[{"access_level":"open_access","file_name":"Thesis_final_PDFA_RoshanPrizak.pdf","file_size":20995465,"content_type":"application/pdf","creator":"rprizak","relation":"main_file","file_id":"6072","checksum":"e60a72de35d270b31f1a23d50f224ec0","date_updated":"2020-07-14T12:47:18Z","date_created":"2019-03-06T16:05:07Z"},{"relation":"source_file","file_id":"6073","title":"Latex files","date_updated":"2020-07-14T12:47:18Z","date_created":"2019-03-06T16:09:39Z","checksum":"67c2630333d05ebafef5f018863a8465","file_name":"thesis_v2_merge.zip","access_level":"closed","content_type":"application/zip","file_size":85705272,"creator":"rprizak"}],"publication_identifier":{"issn":["2663-337X"]},"month":"03","oa":1,"project":[{"call_identifier":"FWF","name":"Biophysics of information processing in gene regulation","grant_number":"P28844-B27","_id":"254E9036-B435-11E9-9278-68D0E5697425"}],"doi":"10.15479/at:ista:th6071","language":[{"iso":"eng"}],"supervisor":[{"full_name":"Tkačik, Gašper","last_name":"Tkačik","first_name":"Gašper","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"}],"degree_awarded":"PhD","file_date_updated":"2020-07-14T12:47:18Z","year":"2019","publisher":"Institute of Science and Technology Austria","department":[{"_id":"GaTk"},{"_id":"NiBa"}],"publication_status":"published","related_material":{"record":[{"id":"1358","status":"public","relation":"part_of_dissertation"},{"status":"public","relation":"part_of_dissertation","id":"955"}]},"author":[{"last_name":"Prizak","first_name":"Roshan","id":"4456104E-F248-11E8-B48F-1D18A9856A87","full_name":"Prizak, Roshan"}],"date_updated":"2023-09-22T10:00:48Z","date_created":"2019-03-06T16:16:10Z"}]