Juillet 2022
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Vendredi 01/07/2022 Salle SDT CRC Séminaire Externe |
« Molecular mechanisms and chromatin determinants of chromosome folding in yeast » | |
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Romain KOSZUL (Institut Pasteur – Paris)
Hôte : Equipe Piazza
Advances in chromosome imaging and Hi-C approaches over the past decade have shown unequivocally that prokaryotic, archaeal, and eukaryotic chromosomes are not folded at random. The principles that govern the 3D organization of genomes, and its causal relationships with DNA processes such as transcription, repair or replication, are being actively studied. Converging evidence indicates that transcription, structural maintenance of chromosomes (SMC) ring-shaped protein complexes and heterochromatin play a major role in chromosome folding. In humans, SMC cohesin mediates chromatin loops that bring together distal regulatory elements and gene promoters. Similar cohesin-mediated loops compact the chromosome during metaphase of budding yeast mitosis (1). The cohesin ring organizes genomes by progressively expanding small DNA loops into larger structures, a ubiquitous process also called loop extrusion (2). Transcription and the deposition of DNA-binding proteins are involved in the positioning of loops, which can also be affected by discrete double-strand breaks (3,4). Recent in vitro single-molecule experiments suggest that loop expansion is mediated by Scc2-stimulated ATPase activity of cohesins.
We now provide a comprehensive overview of the roles of various cohesin regulators in the regulation of chromatin loop expansion in vivo. First, we demonstrate that Scc2 is essential for cohesin translocation, resulting in loop expansion (5). Acetylation of Smc3 during S phase counteracts this activity by stabilizing Pds5, which fine-tunes loop size and stability in G2. Then, we developed a transversal approach to address the limitations resulting from the complex nature of chromosomes, which exhibit an intertwined, multiscale network of structures. We study the behavior of large pseudo-random sequences using Mb long bacterial chromosomes cloned into the yeast genome, from which they have diverged for over 1.5 billion years. We characterized these chimeric genomes using RNA-seq, ChIP-seq, Hi-C, and engineering experiments supported by deep learning analysis to study the determinants of chromosome metabolism, and validate or identify the rules of chromosome folding regulation
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Lundi 04/07/2022 Salle SDT CRC Séminaire Externe |
" Muscle formation, growth and fusion: a bird's eye view " | |
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Prof. Christophe MARCELLE (MeLiS, Lyon, France)
Hôte: Samir MERABET
Christophe has a long and worldwide renowned contribution on muscle formation and repair in vertebrates (see the selected publication list below and his web site: https://inmg.fr/melis/en/team_marcelle.php).
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Lundi 04/07/2022 Amphi Pasteur Séminaire Externe |
« Discovery and development of Hepcludex/bulevirtide, the first approved drug for chronic Hepatitis D virus Infection » | |
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Pr. Stephan URBAN (Dpt. of Infectious Diseases, University Hospital Heidelberg Molecular Virology & German Centre for Infectious Research (DZIF))
Contact: David Durantel
Hepatitis B (HBV) and Hepatitis D Virus (HDV) infection requires the interaction of the shared envelope proteins with the hepatocyte specific receptor sodium taurocholate co-transporting polypeptide (NTCP). This speciesspecific interaction is mediated by an evolutionary adaptation of an essential sequence (the receptor binding domain (RBD)) within the myristoylated preS1-domain of the HBV large surface protein (L-protein) to NTCP.
Following the concept that chemically synthesized lipopeptides representing this RBD are potent inhibitors of hepadnaviral infection, both the identity of the long-sought HBV receptor was uncovered and the first approved entry inhibitor for HBV/HDV infection (bulevirtide/Hepcludex) was developed.In this lecture I will provide a survey on the development of bulevirtide (formerly called Myrcludex B). I will highlight the initial limitations that HBV research faced at a time when only the duck hepatitis B virus (DHBV) infection system was available to study hepadnaviral entry processes. I will elaborate on the transfer of the concepts established in the DHBV model to HBV using primary human hepatocytes (PHH) and HepaRG cell lines. Although some of these concepts could not be verified in both infection systems one finally resulted in the identification of a peptidic lead substance that entered into clinical trials (bulevirtide) in 2011. I will further highlight some very surprising findings that were associated with the pharmacological behaviour of HBVpreS-1- derived peptides in vivo (e.g. liver targeting, stability) that fundamentally differed from other therapeutically applied peptides. I will finally summarize arguments that strongly support the use of an entry inhibitor to counteract HDV (and probably HBV) persistence and therefore may lead to elimination of the respective viral template (nuclear circHDV RNA and HBV cccDNA). The development of bulevirtide was an untypical enterprise, not only regarding its identification as an optimized “fragment” of an “endogenous” viral structure but also regarding its unusual properties as a stable and highly efficient peptidic drug. Its recent approval in the European Union and its successful application to HDV/HBV coinfected patients raises justified hope to become part of a curative regimen in the future. |
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Lundi 08/07/2022 11H00 Salle de conférences IBCP Séminaire Externe |
« Biotherapies for RDEB (Recessive Dystrophic Epidermolysis Bullosa) » | |
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Matthias TITEUX (Inserm U1163 - Institut Imagine – Paris)
Hôte : Catherine Moali
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Vendredi 08/07/2022 14H00 SdT CRC Séminaire externe |
« Nuclear magnetic resonance for plants : fascination of imaging » | |
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Pr. Ljudmilla BORISJUK (IPK Gatersleben ; Leibniz Institute)
Host :
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Mardi 12/07/2022 11h15 Salle SDT CRC Séminaire externe |
« Expansion microscopy for Structural cell biology: from centriole architecture to human diseases » | |
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Pr. Paul GUICHARD (Dpt. of Cell Biology; University of Geneva)
Contact: Chloé Journo & Jacques Brocard
The centriole is an evolutionary conserved organelle that coordinates fundamental biological processes including cell division, cellular signalling and cell motility. This organelle, of 500 nm long and 250 nm in diameter is composed of about 100 different proteins, some of which have been associated with human diseases. How these proteins are organized at the level of the centriole architecture and how associated mutations could be involved in pathologies is still poorly understood. I will present the latest work from my laboratory, which tackle these fundamental structural cell biology questions using cryo-tomography, cell biology and our newly developed ultrastructure expansion microscopy (U-ExM) method
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