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Structural and functional studies on epigenetic regulators

Abstract : This manuscript describes my research activities over the last fifteen years. I graduated in Molecular Biology from the Charles University in Prague in 2000. At that time, structural biology was very poorly developed in my home country. During my training at EMBL in Grenoble I discovered for the first time the world of protein structures and realized how important detailed structural information can be to understand protein function. I then joined the laboratory of Stephen Cusack at the EMBL and began my PhD jointly with the Université Joseph Fourier. I started using X-ray crystallography and studied proteins involved in targeted mRNA degradation pathway called the Nonsense Mediated mRNA Decay. For my postdoc I decided to change the research filed and joined the group of David Stuart at the University of Oxford to work on viral fusion proteins. The preparation of these viral surface glycoproteins for crystallization required their expression in mammalian cells and an efficient deglycosylation. The scientific, instrumentation and technological environment at the department was truly exceptional so it was possible to succeed in these projects in a relatively short time. The structure of the baculovirus fusion protein GP64 we determined was perhaps the most revealing structure I have worked on so far and was a significant contribution to the viral fusion field. While working in Oxford was a great experience I decided to return to France and was offered a staff scientist position back at EMBL Grenoble in my original PhD laboratory. I was very fortunate to be given a maximal scientific independence and support within the group. I established a new research line in the group focusing on epigenetic regulatory complexes. Chromatin/epigenetic control of DNA-based processes is an extremely important and sophisticated layer of regulation. Perhaps, due to the challenging nature of chromatin regulatory complexes for structural analysis, most of them still remain structurally uncharacterised. I started two very fruitful collaborations with expert cell biologist in the chromatin field, Asifa Akhtar (MPI Freiburg) and Bernard de Massy (IGH Montpellier). Together with them we can carry out an interdisciplinary research combining biochemistry, structural and cell biology and genetics. All my work on the histone acetyltransferase complexes (MSL and NSL complex) and PRDM9 at the EMBL included supervision of Master and PhD students. In 2014, I obtained the ATIP/AVENIR start-up grant and moved to the Institut de Biologie Structurale (IBS) in Grenoble where I set up my research team. We continue our effort to structurally and functionally characterise the MSL and NSL complexes as well as the PRDM9 methyltransferase. Given the large size of these complexes, the method of choice for the analysis will be a combination of X-ray crystallography and cryo-electron microscopy.
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https://hal.univ-grenoble-alpes.fr/tel-02440134
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Soumis le : mercredi 15 janvier 2020 - 08:31:58
Dernière modification le : mercredi 15 juillet 2020 - 13:02:04
Archivage à long terme le : : jeudi 16 avril 2020 - 12:44:28

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  • HAL Id : tel-02440134, version 1

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Jan Kadlec. Structural and functional studies on epigenetic regulators. Biomolecules [q-bio.BM]. Université Grenoble Alpes, 2017. ⟨tel-02440134⟩

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