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Séminaire

  • Génomes

    • Vendredi 16 mars 11:00-12:00 - Damien Coudreuse - Institut de Génetique & Développement de Rennes

      Shaping cell proliferation : cell cycle progression and CDK activity dynamics

      Résumé : Cell cycle progression is central to cell proliferation in normal and pathological contexts. Despite the complexity of the eukaryotic cell cyclecontrol, we previously showed that the core engine of cell proliferation relies on the simple oscillation of a single qualitative cyclin-dependent kinase (CDK) activity between a low (S phase) and high (M phase) threshold. While this model explains the main cell cycle transitions, the importance of the temporal profile of CDK activity remains unknown. In other words, do the precise dynamics in CDK function throughout the cell cycle play a role in the integrity of cell proliferation, as was suggested by mathematical models ? Or is the two-threshold model sufficient to understand how eukaryotic cells organise their cell cycle ? Using a synthetic approach to cell cycle control in fission yeast coupled with high resolution microscopy and microfluidic technologies, our recent work reveals how CDK activity dynamics shape cell cycle progression and act as a noise filter.
      Contact : Julie SOUTOURINA <julie.soutourina cea.fr>

      Lieu : Auditorium - bâtiment 21 - Campus CNRS de Gif-sur-Yvette

      Article

    • Vendredi 23 mars 11:00-12:00 - Antoine Coulon - Genome functions in space and time, Institut Curie - CNRS

      Probing the spatiotemporal kinetics of transcription at the single-RNA level

      Résumé : The synthesis of mature messenger RNA molecules from the DNA sequence of a gene is a central step in gene expression and is regulated at many levels (transcription initiation, elongation, splicing...). Yet, at the single-gene level, the stochastic kinetics of such regulatory processes and their coordination in space and time remain poorly understood.
      Using the RNA-labeling techniques MS2 and PP7, we can now image transcription “in 4D” to probe the processes involved in mRNA synthesis. More specifically, with this approach, we are able to visualize and monitor in real-time the position and the amount of nascent transcripts from individual genes of interest, with high temporal resolution and single-molecule sensitivity. The possibility of using two colors (e.g. to label either two distinct parts of a single gene or two different genes) opens up a vast range of possibilities to study the kinetics and coordination between the molecular mechanisms involved in transcriptional regulation. A methodological challenge is the analysis and interpretation of the resulting datasets, i.e. stochastic and noisy transcriptional time traces. To this end, we also developed a computational method based on auto/cross-correlation analysis to reveal the signatures of the underlying molecu­lar processes and extract quantitative information about single-RNA transcription kinetics.
      I will present these imaging and data analysis approaches and how we applied them to understand the kinetics of single-RNA synthesis, sense/antisense transcription and gene bursting, as well as our future directions to study transcriptional coordination in four dimensions.
      Contact : Daan Noordermeer <daan.noordermeer i2bc.paris-saclay.fr>

      Lieu : Bibliothèque- bâtiment 34 - Campus CNRS de Gif-sur-Yvette

      Article

    • Vendredi 30 mars 14:00-15:00 - Gisou Van der Goot - Ecole Polytechnique Fédérale de Lausanne

      Function and dynamics of protein palmitoylation

      Résumé : Protein function can be regulated by a variety of post-translational modifications. One that is of particular interest, but still poorly understood due to the technical difficulties in studying it, is S-acylation, the only reversible lipid modification of proteins. Over recent years it has become apparent that 10% or more of the human proteome can undergo this modification. It is mediated by polytopic transmembrane enzymes of the DHHC family of which human have 23, flies and worms about 20. Mutations in these enzymes have been associated with higher brain function disorders and cancer. Removal of the acyl chain occurs through the action of Acyl Protein thioesterases, of which so far 5 have been identified.
      The presentation will be focused on palmitoylation in the endoplasmic reticulum, where a variety of key functions are regulated by palmitoylation. I will describe how the architecture of the compartment is controlled by palmitoylation via the ZDHHC6 palmitoyltransferase. This indicates that the activity of this enzyme needs to be tightly regulated. I will show that it is in fact controlled by a cascade of palmitoylation, reminiscent of the cascades observed in phosphorylation and ubiquitination.
      Contact : Carmela GIGLIONE <carmela.giglione i2bc.paris-saclay.fr>

      Lieu : Bibliothèque- bâtiment 34 - Campus CNRS de Gif-sur-Yvette

      Article

  • Biologie Cellulaire

    • Vendredi 9 mars 11:00-12:00 - Damien ARNOULT - Institut André Lwoff, Villejuif, invité par Agnès Delaunay-Moisan

      A cytosolic unfolded protein response controls innate immune signaling

      Lieu : Auditorium - bâtiment 21 - Campus de Gif-sur-Yvette

      Article

    • Vendredi 16 mars 11:00-12:00 - Guy TRAN VAN NHIEU - CIRB, Paris, invité par R. Legouis

      Ca2+ signals and cytoskeletal reorganization during Shigella invasion of epithelial cells

      Résumé : The bacterial pathogen Shigella invades the colonic mucosa, triggering tissue destruction leading to the dysenteric syndrome. We will review how this pathogen promotes its invasion and intracellular replication by affecting cellular processes that regulate cytoskeletal dynamics, vesicular trafficking and the autophagy machinery. Recent findings highlighting the key role of bacterial effectors that divert host cell mechanosensing and Ca2+ signaling will be presented.

      Lieu : Bibliothèque - bâtiment 34 - campus de Gif-sur-Yvette

      Article

    • Lundi 26 mars 11:00-12:30 - Ivan BAXTER - Donald Danforth Plant Sciences Center, St Louis (MO) USA

      Can We Use Elemental Profiles to Understand How Plants Adapt to Their Environments ?

      Résumé : Contact : Sebastien.THOMINE i2bc.paris-saclay.fr

      Lieu : Auditorium I2BC - Bât. 21, Campus de Gif-sur-Yvette

      Article

    • Vendredi 30 mars 11:00-12:00 - Manuel THERY - Institut Universitaire d'Hematologie, Hopital Saint Louis, Paris, invité par A.M. Tassin

      Making sense of symmetry breaks

      Résumé : In this presentation I will discuss the role of friction in and on actin and microtubule networks. I will describe few examples showing that friction in the networks tend to maintain the symmetry whereas friction on the networks tend to break it. I will discuss how these geometrical rules propagate to the overall cell polarity via actin-microtubule crosstalk.

      Lieu : Bibliothèque - bâtiment 34 - Campus de Gif-sur-yvette

      Article

  • I2BC

    • Mercredi 7 mars 11:00-12:30 - Rati Fotedar - Sanford Burnham Prebys Medical Discovery Institute, San Diego, California, USA

      Braking the cell cycle : some twists and turns

      Résumé : Our contributions to the mammalian cell cycle and DNA damage fields have defined the role and mechanisms of protein modification and protein degradation in regulation of the cell cycle, DNA replication and DNA damage/repair. We have focused on proteins regulating the cell cycle (CDKs, Rb, Emi1), DNA replication (RPA, RFC, PCNA), DNA damage checkpoint (p53, p21, Emi1, WISp39, Hsp90, APC), DNA repair pathways (NER, MMR), mitosis (APC) and stress signaling (MAPK, mTOR). Our work has provided insights into the biochemical and molecular framework of DNA damage signaling by the p53 tumor suppressor as well as the role of Hsp90 and of an E3 ubiquitin ligase in this process. Cell cycle regulation is crucial for normal development, for differentiation and for tumorigenesis. I will describe recent work in which we identified a previously unknown mechanism of how CDKs regulate cell cycle progression. Finally, while cell cycle arrest is required for senescence, it is not sufficient by itself to induce this state. Our recent work reveals signals that act downstream of cell cycle arrest to induce senescence.


      Invité par Thierry Meinnel

      Lieu : Auditorium I2BC - Bâtiment 21
      Campus de Gif-sur-Yvette

      Article

  • Virologie

    • Mardi 20 mars 11:00-12:30 - Franck Perez - Institut Curie, Paris

      Exploring and Exploiting the Diversity of Secretory Routes in Mammalian Cells

      Résumé : To regulate their homeostasis – to exchange signals with the extracellular environment or migrate for example – cells need to address particular proteins and lipids toward specific compartments in a tightly controlled way. Golgi-dependent trafficking plays an essential role in these processes but, although our knowledge about the mechanisms of intra-Golgi transport and sorting has dramatically increased over the past two decades, the underlying complexity of transport routes, in term of mechanism and dynamics, is only starting to emerge.
      Using our recently developed synchronized secretory system, the RUSH assay, we monitored transport of cargos to the cell surface and observed that preferred tracks exist in cells that drive protein transport to exocytosis hotspots. We also used the RUSH system to explore cell-to-cell signalling analysing the transport of GPI-anchored ephrins. Last, we are adapting the RUSH assay for High Content Screening to use the diversity of the secretory pathway to identify potential therapeutic molecules.

      Lieu : Salle de séminaire bâtiment 14C - Campus Gif-sur-Yvette

      Article

    • Mardi 27 mars 11:00-12:30 - Wolfram Brune - Heinrich Pette Institute, Leibniz Institute for Experimental Virology

      Viral induced protein aggregation and selective autophagy for the inhibition of cell death and inflammation

      Résumé : Murine cytomegalovirus (MCMV) encodes a multifunctional protein called M45. This protein interacts with receptor-interacting protein kinase 1 (RIPK1) and RIPK3 to inhibit the induction of programmed necrosis in response to viral infection. M45 also blocks proinflammatory NF-κB signalling by interacting with the regulatory subunit of the IKK complex, NEMO, and redirecting it to autophagosomes. However, the molecular mechanism of autophagy induction and selective NEMO degradation by M45 remained to be determined. We now show that degradation occurs in two steps. First, M45 interacting with NEMO and RIPK1 causes their accumulation in the detergent insoluble fraction, most likely as misfolded protein aggregates. A conserved sequence motif with the C-terminal part of M45 was identified as responsible for this process. In the second step, insoluble aggregates are targeted to autophagosomes for degradation in lysosomes. This process requires the interaction of M45 with Vps26B, a component of the retromer complex. Vps26B serves as a selective autophagy receptor by interacting with the key autophagy marker LC3-II via the adaptor protein TBC1D5. Indeed, we show that M45-induced NEMO and RIPK1 degradation was inhibited in Vps26b or TBC1D5 deficient cells. Collectively the data suggest that M45 recruits the retromer component Vps26B to promote the degradation of insoluble NEMO and RIPK1 aggregates via the adaptor protein TBC1D5.

      Lieu : Salle de séminaire bâtiment 14C - Campus de Gif-sur-Yvette

      Article

  • Microbiologie

    • Jeudi 15 mars 11:30-13:00 - Dr. Xavier Charpentier - Centre International de Recherche en Infectiologie (CIRI), Lyon

      Silently transformable : how bacteria conceal their built-in capacity of genetic exchange

      Résumé : A highly conserved DNA uptake system allows some bacteria to actively import and integrate exogenous DNA. This process, called natural transformation, represents a major mechanism of horizontal gene transfer (HGT) and is involved in the acquisition of virulence and antibiotic resistance determinants. Despite evidence of widespread HGT and the high level of conservation of the genes coding the DNA uptake system, most bacterial species appear non-transformable under laboratory conditions. This observation led us to investigated the mechanism that controls expression of the DNA uptake system in the human pathogen Legionella pneumophila (1). We found that expression of the DNA uptake system is controlled by a novel RNA-based silencing system. Silencing is relieved under specific conditions, allowing bacteria to take up free DNA and subsequently undergo genetic transformation. RNA-based silencing represents a previously unknown regulatory means to control natural transformation (2). Importantly, these findings also show that a previously overlooked family of chromosome-encoded proteins act as chaperones of trans-acting sRNAs, playing key roles in post-transcriptional gene regulation throughout bacterial species (3). Also, and in light of unpublished results, a recent hypothesis suggesting that natural transformation evolved as mechanism to rid the genome of selfish genetic elements will be discussed.
      1. Attaiech L, Boughammoura A, Brochier-Armanet C, Allatif O, Peillard-Fiorente F, Edwards RA, Omar AR, MacMillan AM, Glover M, Charpentier X. 2016. Silencing of natural transformation by an RNA chaperone and a multitarget small RNA. Proc Natl Acad Sci U S A 113:8813–8818.
      2. Attaiech L, Charpentier X. 2017. Silently transformable : the many ways bacteria conceal their built-in capacity of genetic exchange. Curr Genet 63:451–455.
      3. Attaiech L, Glover JNM, Charpentier X. 2017. RNA Chaperones Step Out of Hfq’s Shadow. Trends Microbiol 25:247–249.


      Invited by Tamara Basta-Le Berre

      Lieu : Salle Kalogeropoulos - Bâtiment 400, Campus d’Orsay

      Article

  • B3S

    • Jeudi 8 mars 10:30-12:00 - Hélène Launay - iSCB (Integrative Structural &Chemical Biology), Marseille

      Structural disorder and photosynthesis regulation deciphered using NMR, SAXS and Modelling

      Résumé : Photosynthesis is the only mean of regulation of terrestrial CO2, and its regulation is mediated via protein-protein interactions, post-translational modifications and disorder-to-order transitions. One of the central regulators of the chemical photosynthesis pathway, the Calvin-Benson-Basham cycle, is the conditionally disordered chloroplastic protein CP12. During the day, reducing conditions prevail in the chloroplast and reduced CP12 is intrinsically disordered. During the night, oxidizing conditions prevail in the chloroplast, CP12 is oxidized, and the protein binds to and inhibits to key players of the CBB cycle : glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and phosphoribulokinase (PRK). I will present our recent structural investigation of the Chlamydomonas reinhardtii CP12 using NMR, SAXS, molecular modelling, CD, which show that CP12 is a very peculiar intrinsically disordered protein that undergo several disorder-to-order transitions depending on either its redox state or its association with its partner. CP12 is a model conditionally disordered protein, and the molecular description of its disorder-to-order transitions are required to rationalize the fine tuning of photosynthesis and carbon assimilation in micro-algae.

      Lieu : Bibliothèque, Bât. 34 - Bâtiment 34, Campus Gif-sur-Yvette

      Article

    • Vendredi 30 mars 11:00-12:30 - Ludovic Sauguet - Institut Pasteur, Unité de Dynamique Structurale des Macromolécules

      Secret from the abyss : crystal and cryo-EM structures of the D-family DNA polymerase (PolD) reveal that DNA replication and DNA transcription share a joint evolutionary history in archaea

      Résumé : Archaeal replicative DNA polymerases D (PolD) constitute an atypical class of DNA polymerases. Crystal and Cryo-EM structures of Pyrococcus abyssi PolD reveal a catalytic core strikingly different from all other known DNA polymerases. Rather, the PolD catalytic core has the same “double-psi b-barrel” architecture seen in the RNA polymerase (RNAP) superfamily, which includes multi-subunit transcriptases of all domains of life. This finding bridges together, for the first time in cellular life, DNA transcription and DNA replication within the same protein superfamily.

      En raison des conditions d’accès sur le Centre d’Etudes de Saclay, les personnes qui désirent assister à ces conférences sont invitées à contacter Jean-Baptiste Charbonnier (Tél. : 01 69 08 76 77) au moins 3 jours avant la date de la conférence pour les citoyens de l’Union Européenne ou au moins 20 jours pour les citoyens hors Union Européenne. A la porte Nord (accès par la D36), ces personnes devront présenter une pièce d’identité prouvant leur nationalité et devront préciser qu’elles viennent assister à un séminaire du SB2SM/LBSR.
      Due to the restricted access to the Centre d’Etudes de Saclay, scientists who wish to attend these seminars should call Jean-Baptiste Charbonnier (Tel : 01 69 08 76 77) at least 3 days before the date of the conference for EU citizens or at least 20 days for non-EU citizens. At the North entrance (D36 road), these scientists will have to present a passport to prove their nationality and state that they will attend the seminar of the SB2SM/LBSR.

      Lieu : Salle de conférence du Bat 144, CEA, CE-Saclay. - I2BC, Site Saclay

      Article

  • Club Bioinformatique

    • Lundi 12 mars 11:00-12:30 - (i) Cyril Denby-Wilkes (ii) Mariam Bouzid - (i) I2BC (ii) I2BC

      (i) Transcription-coupled DNA repair (ii) Very fast taxonomic comparison of genomic sequences

      Résumé : (i) Cyril Denby-Wilkes (eq. Julie Soutourina/I2BC)
      Genome-wide study of transcription-coupled DNA repair in response to UV-irradiation
      (ii) Mariam Bouzid (SSFA/I2BC)
      A tool for very fast taxonomic comparison of genomic sequences

      Lieu : salle de conférence A.Kalogeropoulos - b.400, campus Orsay - Université Paris-Sud, 91405 - Orsay Cedex

      Article

  • cytoskeleton club

    • Mardi 20 mars 11:45-12:30 - Anne-Marie Pret

      Cytoskeleton club

      Résumé : JAK/STAT Signaling and Epithelial Dynamics

      Lieu : Bibliothèque - Bâtiment 34, campus de Gif

      Article

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