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  • Génomes

    • Lundi 2 septembre 11:00-12:00 - Chloé GIRARD - Stanford University, USA

      Recombining genomes : when, where and how much ?

      Résumé : Meiotic recombination is a major driving force of evolution : not only can it create new and advantageous genetic combinations, but it can also break down existing ones. The frequency and distribution of crossovers dictate which traits are inherited together and which ones are re-assorted to produce new combinations on which selection can act. Crossover distribution is neither uniform nor random, but the mechanisms and evolutionary forces that impose crossover patterning are poorly understood. Understanding when, where, and how much genomes recombine is of major importance to apprehend causes of infertility and to reveal the forces contributing to genome evolution. Chloe Girard has been studying the mechanisms that regulate meiotic recombination in both the plant Arabidopsis and the nematode C. elegans, and will share insights about factors that limit crossover formation in wild type. She will also present future directions for her research about how crossover distribution and frequency can be influenced by polymorphism density and external stress conditions.

      Lieu : Salle A. Kalogeropoulos - bâtiment 400 - campus d'Orsay

      Article

    • Mardi 10 septembre 11:00-12:00 - Céline VALLOT - Institut Curie, Paris

      Tracking the dynamics of chromatin states in tumor cells at single-cell resolution : response and resistance to cancer therapies

      Résumé : The dynamic nature of chromatin and transcriptional features are expected to participate to tumor evolution, particularly in the context of response to cancer treatment and acquisition of resistance. Yet, the contribution of epigenetic plasticity to cancer cells remains unclear and means to target it are still rather non-specific and inefficient, mostly due to the lack of relevant cellular models and in vivo datasets. We have recently achieved the mapping of histone marks at single-cell resolution in human breast tumors, enabling the investigation of the dynamics of chromatin marks, and its contribution to tumor evolution. Using in vivo models of acquired resistance to cancer treatment, our recent data indicate that resistance to tamoxifen or chemotherapy may be associated with the emergence of an epigenetic subclone, characterized by a specific histone mark profile that could be stable along cell generations. More generally, the research projects of the group aim for a better understanding of the mechanisms of non-genetic selection, with the objective to design strategies to enhance or restore sensitivity to cancer treatments.

      Lieu : Salle A. Kalogeropoulos - bâtiment 400 - campus d'Orsay

      Article

    • Vendredi 20 septembre 11:00-12:00 - Christian MUCHARDT - Institut Pasteur, Paris

      Regulation of transcription initiation and mRNA maturation by silencing machineries

      Résumé : Machineries imposing long-term transcriptional repression – or transcriptional gene silencing – are essential to prevent expression of repeated and potentially mobile DNA elements, and to ensure the timely and robust transcriptional repression of genes involved in cell differentiation and development. Yet, silencing machineries also participate in transcriptional regulation of inducible genes. In particular, many genes involved in innate immune defense are regulated by members of the HP1 family, keeping them in check in the absence of stimulation, but also regulating their alternative splicing while they are expressed. These mechanisms will be discussed in the context of autoimmune diseases and ageing.


      Contact : BETERMIER Mireille (Mireille.BETERMIER i2bc.paris-saclay.fr)

      Lieu : Salle des séminaires - bâtiment 26 - campus de Gif-sur-Yvette

      Article

    • Vendredi 27 septembre 11:00-12:00 - Frederic FROTTIN - Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany

      Phasing-in protein quality control in the nucleus : the nucleolus is a phase-separated protein quality control compartment with novel chaperone-like properties.

      Résumé : Protein quality control in the nucleus is not well understood. The nucleus contains several non-membrane bound subcompartments forming liquid-like condensates. The largest of these is the nucleolus, the site of ribosome biogenesis. Metastable nuclear proteins that misfold upon heat stress enter the nucleolus where they avoid irreversible aggregation and remain competent for Hsp70 dependent refolding upon recovery from stress. Prolonged stress or the uptake of proteins associated with neurodegenerative diseases resulted in loss of reversibility. These findings demonstrate how the properties of a phase-separated compartment can be utilized in protein quality control, a fundamental biological function.
      Recent publications :
      The nucleolus functions as a phase-separated protein quality control compartment.
      Frottin F, Schueder F, Tiwary S, Gupta R, Körner R, Schlichthaerle T, Cox J, Jungmann R, Hartl FU, Hipp MS.
      Science. 2019 Jul 11. pii : eaaw9157. doi : 10.1126/science.aaw9157. [Epub ahead of print]
      In Situ Structure of Neuronal C9orf72 Poly-GA Aggregates Reveals Proteasome Recruitment.
      Guo Q, Lehmer C, Martínez-Sánchez A, Rudack T, Beck F, Hartmann H, Pérez-Berlanga M, Frottin F, Hipp MS, Hartl FU, Edbauer D, Baumeister W, Fernández-Busnadiego R.
      Cell. 2018 Feb 8 ;172(4):696-705.e12. doi : 10.1016/j.cell.2017.12.030. Epub 2018 Feb 1.
      Soluble Oligomers of PolyQ-Expanded Huntingtin Target a Multiplicity of Key Cellular Factors.
      Kim YE, Hosp F, Frottin F, Ge H, Mann M, Hayer-Hartl M, Hartl FU.
      Mol Cell. 2016 Sep 15 ;63(6):951-64. doi : 10.1016/j.molcel.2016.07.022. Epub 2016 Aug 25.

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

      Article

  • Biologie Cellulaire

    • Mardi 10 septembre 11:30-12:30 - Mikael MOLIN - Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden

      Roles of peroxiredoxins in proteostasis and longevity converge on protein biosynthesis

      Résumé : Peroxiredoxins are modulators of aging in yeast and multicellular organisms (1). We have previously identified key roles for the peroxiredoxin Tsa1 in mechanisms by which caloric restriction (CR) boosts yeast H₂O₂ stress resistance and slows down replicative aging (2,3). Our data point to a role of peroxiredoxins as modulators of signaling that appears to be crucial for their ability to slow down aging and stimulate H₂O₂ resistance (4-6). In addition, we have shown that peroxiredoxins elicit a key role in age-related proteostasis (3), which is interesting given the conservation of proteostatic dysfunction in neurodegeneration and age-related decline.
      Strikingly, we found that increased dosage of the major cytosolic Prx in yeast, Tsa1, potently extends lifespan in an Hsp70 chaperone-dependent and CR-independent manner without altering H2O2 levels or genome stability (3). Furthermore, Tsa1 and Hsp70 interact physically and hyperoxidation of the primary catalytic (peroxidatic) cysteine in Tsa1 by H2O2 is required for the recruitment of Hsp70 chaperones and the Hsp104 disaggregase to misfolded and aggregated proteins during peroxide stress and aging but not heat stress. In addition, the reduction of hyperoxidized Tsa1 by sulfiredoxin facilitated clearance of H2O2-generated aggregates.
      Still the ability of Tsa1 to counteract aging and to stimulate H2O2-resistance depends on the activity of both the peroxidatic and the resolving catalytic cysteines (6). A recent closer investigation of aggregates forming in cells upon H2O2 addition reveal that they are more mobile than those forming upon heat-shock and co-accumulate certain mRNAs, suggesting that they represent translation-related messenger RiboNucleoProtein complexes (mRNPs). Through a novel, non-invasive technique for ribosome profiling (5P-Seq) we can substantiate a role of Tsa1 in regulating global protein synthesis. In addition, we found that ribosomes pause in a Tsa1-dependent manner at a specific codon upon H2O2 addition. We are currently looking into to what extent modulating tRNA levels affects Tsa1-dependent phenotypes.
      References
      1. Nystrom, T., 2012. Genes & Development, 26 : 2001-8.
      2. Molin, M., 2011. Molecular Cell, 43 : 823-33.
      3. Hanzen, S. 2016. Cell, 166 : 140-51.
      4. Goulev, Y., 2017. eLIFE, 6 : 23791
      5. Bodvard, K., 2017. Nature Communications, 8 : 14791
      6. Roger F., 2019. bioRxiv, 676270

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

      Article

  • Virologie

    • Vendredi 20 septembre 11:00-12:00 - Quentin NEVERS - Institut Pasteur, Paris

      IFITM proteins inhibit cell-cell fusion mediated by endogenous retroviral envelopes

      Lieu : Salle des séminaires - Bâtiment 14C, Campus de Gif-sur-Yvette

      Article

  • B3S

    • Vendredi 6 septembre 11:00-12:00 - Tomio Takahashi - Equipe Biologie Cellulaire des Archées, I2BC

      Identification of new topoisomerase and topoisomerase-like proteins in mobile genetic elements

      Résumé : The control of DNA topology by DNA topoisomerases is essential for fundamental cellular processes, such as transcription and replication. These enzymes, ubiquitous and essential for every organism, exist as several non-homologous families. We previously identified a small group of atypical type IIB DNA topoisomerases, called Topo VIII, mainly encoded by free or integrated plasmids from bacteria. Taking advantage of the rapid expansion of sequenced genomes, we found new putative Topo VIII sequences. Further analysis confirm and expand the presence of the corresponding genes in mobile genetic elements across nine different bacterial phyla and one archaeal superphylum. We notably identified a new subfamily of enzymes called "Mini-A" in free and integrated bacterioviruses and archaeoviruses, that are homologous but distantly related to other type IIB topoisomerases. Interestingly, one uncharacterized peptide at the C-terminal extremity of type IIB enzymes seems sufficient to discriminate between the three subfamilies, Mini-A, Topo VI and Topo VIII. This "Type 2 topoisomerases Interaction" T2I box could be one key element to understand the difference between these subfamilies. Altogether, this work leads to an updated model for the origin and evolution of type IIB topoisomerase family and raise questions concerning the function of topoisomerases for mobile genetic elements.

      Lieu : Salle de conférence - Bat 144, Campus CEA Saclay

      Article

    • Mardi 24 septembre 11:00-12:00 - Joanna Timmins - IBS, Univ. Grenoble Alpes, CNRS, CEA

      Nucleoid organisation and dynamics in Deinococcus radiodurans

      Résumé : In all organisms, genomic DNA is compacted several orders of magnitude and yet must remain accessible for essential DNA-related processes. Using a combination of biochemical, biophysical and advanced imaging approaches, we have explored the nucleoid organization in Deinococcus radiodurans, a relatively large, spherical bacterium, well-known for its exceptional radioresistance. This work has revealed that its nucleoid is highly compact, but also surprisingly dynamic, adopting various configurations, including the previously described toroid. A major player in the organization of bacterial nucleoids is the highly abundant histone-like HU protein that largely coats the genomic DNA. We have investigated HU’s mode of DNA binding and its ability to condense the genomic DNA. Taken together, these findings demonstrate that bacterial nucleoids are tightly regulated by cell shape and cell cycle progression, and suggest that the HU protein plays a key role in this process.

      Lieu : Salle de conférence - Bat 144, Campus CEA Saclay

      Article

  • cytoskeleton club

    • Mardi 10 septembre 11:30-12:30 -

      Cytoskeleton club - Internal seminar

      Lieu : Bibliothèque - bât. 34

      Article

Soutenance

  • Microbiologie

    • Lundi 23 septembre 14:00-17:00 - Joy Lachat - Equipe Interactions Plantes-Bactéries, I2BC

      Identification des facteurs de résistance aux peptides antimicrobiens et de colonisation de l’insecte Riptortus pedestris chez la bactérie symbiotique Burkholderia insecticola

      Résumé : L’insecte phytophage Riptortus pedestris, appartenant au sous-ordre des Hétéroptères, est un ravageur notoire de cultures agricoles en Asie du sud-est qui se nourrit préférentiellement de plants de soja. Cette punaise est associée à une bactérie symbiotique du genre Burkholderia nommée Burkholderia insecticola, localisée dans une région spécifique de l’intestin de l’insecte appelée la région M4. Cette région M4, organisée en cryptes, constitue l’organe symbiotique dans lequel le symbiote prolifère de manière extracellulaire. Cette interaction favorise la croissance et le développement de la punaise. Récemment, il a été montré que Riptortus produit des peptides antimicrobiens au sein des cryptes, appelés “crypt-specific cysteine-rich peptides” ou peptides CCR pour lesquels le symbiote est particulièrement résistant. Il a été proposé que les peptides antimicrobiens de l’hôte, incluant les peptides CCR, participent à la colonisation spécifique de l’organe symbiotique par B. insecticola. Dans ce travail, une approche Tn-seq a été utilisée pour identifier les gènes bactériens impliqués dans la résistance aux peptides antimicrobiens et dans la symbiose. Dans un premier temps, la robustesse de la méthode Tn-seq a été évaluée en identifiant le génome essentiel de B. insecticola. Puis dans un second temps, les facteurs bactériens impliqués dans la résistance aux peptides antimicrobiens ont été caractérisés via une approche gènes-candidats et l’approche Tn-seq. Dans une dernière partie, une expérience de Tn-seq in vivo a permis d’évaluer l’ampleur du goulot d’étranglement sur la population symbiotique lors de l’infection de l’organe symbiotique et d’identifier les facteurs symbiotiques impliqués dans la colonisation de R. pedestris.

      Lieu : Bibliothèque - Bâtiment 34, campus Gif-su-Yvette

      Article

    • Lundi 30 septembre 14:00-17:00 - Anna Maikova - Equipe ARNs régulateurs chez les Clostridies, I2BC

      The CRISPR-Cas system of human pathogen Clostridium difficile : function and regulation

      Résumé : Clostridium difficile (the novel name – Clostridioides difficile) is a Gram-positive, strictly anaerobic spore forming bacterium, found in soil and aquatic environments as well as in mammalian intestinal tracts. C. difficile is one of the major pathogenic clostridia and a key public health issue associated with antibiotic therapy in industrialized countries. Since the last decade the number of severe infection forms has been rising due to emergence of the hypervirulent and epidemic strains as ribotype 027 R20291 strain. Many aspects of C. difficile pathogenesis remain poorly understood. During the infection cycle C. difficile survives in bacteriophage-rich gut communities possibly by relying on some special systems that control the genetic exchanges favored within these complex environments. During the last decade, CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) systems of adaptive prokaryotic immunity against exogenic genetic elements has become the center of interest among various anti-invader bacterial defense systems.
      Previous studies revealed the presence of abundant and diverse CRISPR RNAs in C. difficile. C. difficile has an original CRISPR-Cas system, which is characterized by the presence of an unusually large set of CRISPR arrays (12 arrays in the laboratory 630 strain and 9 in the hypervirulent R20291 strain), of two or three sets of cas genes conserved in the majority of sequenced C. difficile genomes and the prophage location of several CRISPR arrays. However, the role CRISPR-Cas plays in the physiology and infectious cycle of this important pathogen remains obscure.
      In the present PhD thesis, the experimental evidence for CRISPR system functionality in C. difficile is provided. Through plasmid conjugation experiments we demonstrate the defensive functions of CRISPR-Cas system in both reference and epidemic C. difficile strains and its adaptive function in reference strain. Additionally, the general functional protospacer-adjacent motif (PAM) consensus was determined using PAM libraries experiments. The role of multiple cas operons in C. difficile CRISPR functionality was also demonstrated.
      New aspects of the regulation of C. difficile CRISPR-Cas system expression and function were explored. This work demonstrates the link between C. difficile CRISPR-Cas system and a new type I toxin-antitoxin system, as well as a possible co-regulation under biofilm and stress conditions of CRISPR-Cas system and these toxin-antitoxin modules. Furthermore, a possible role of c-di-GMP in regulation of C. difficile CRISPR-Cas system was defined.
      Additionally, the utilization of endogenous C. difficile CRISPR-Cas system as a novel tool for genome editing in C. difficile was described.
      Altogether, the obtained data highlight the original features of active C. difficile CRISPR-Cas system and demonstrate its biotechnological potential.

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

      Article

    • Lundi 30 septembre 14:00-17:00 - Céline Aubry - Equipe Microbiologie Moléculaire des Actinomycètes, I2BC

      Vers la biosynthèse combinatoire d’antibiotiques pyrrolamides chez Streptomyces.

      Résumé : Depuis plus de 80 ans, le métabolisme spécialisé nous fournit de nombreuses molécules utilisées en médecine, en particulier comme anti-infectieux. Aujourd’hui, avec l’augmentation mondiale de la résistance aux antimicrobiens, de nouveaux antibiotiques sont indispensables. Une des réponses à cette pénurie grave pourrait provenir de la biologie synthétique. Dans le domaine du métabolisme spécialisé, la biologie synthétique est utilisée en particulier pour la biosynthèse de métabolites non naturels. Parmi les métabolites spécialisés, les peptides non ribosomiques constituent une cible attrayante, car ils nous ont déjà fourni des molécules à haute valeur clinique (ex. les antibiotiques vancomycine et daptomycine). De plus, la plupart sont synthétisés par des enzymes multimodulaires appelées synthétases de peptides non ribosomiques (NRPS), et sont diversifiés davantage par des enzymes de décoration. Ainsi, ces voies de biosynthèse se prêtent particulièrement à la biosynthèse combinatoire, consistant à combiner des gènes de biosynthèse provenant de divers groupes de gènes ou, dans le cas des NRPS, à combiner des modules ou domaines pour créer de nouvelles enzymes. Cependant, si plusieurs études ont établi la faisabilité de telles approches, de nombreux obstacles subsistent avant que les approches combinatoires de biosynthèse soient totalement efficaces pour la synthèse de nouveaux métabolites.
      Les travaux présentés ici s’inscrivent dans le cadre d’un projet visant à comprendre les facteurs limitant les approches de biosynthèse combinatoire basées sur les NRPS, en utilisant une approche de biologie synthétique. Nous avons choisi de travailler avec les NRPS responsables de la biosynthèse des pyrrolamides. En effet, ces NRPS sont constitués uniquement de modules et de domaines autonomes, et donc particulièrement adaptés aux manipulations génétiques et biochimiques. La caractérisation du groupe de gènes de biosynthèse du pyrrolamide anthelvencine constitue la première partie de cette thèse et nous a fourni de nouveaux gènes pour notre étude. La deuxième partie a consisté à construire de vecteurs intégratifs modulaires, outils essentiels pour la construction et l’assemblage de cassettes génétiques. La dernière partie présente la reconstruction du groupe de gènes du pyrrolamide congocidine, basée sur la construction et l’assemblage de cassettes de gènes synthétiques. Dans l’ensemble, ces travaux ouvrent la voie à de futures expériences de biosynthèse combinatoire, expériences qui devraient contribuer à une meilleure compréhension du fonctionnement précis des NRPS.

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

      Article

  • B3S

    • Mardi 24 septembre 14:00-17:00 - Jingqi DAI - Equipe Enveloppe Nucléaire, Télomères et Réparation de l'ADN, I2BC

      Mécanisme moléculaire de l’endonucléase Mlh1-Mlh3 dans la voie de réparation des mésappariements de l’ADN et dans les processus de recombinaison en méiose

      Lieu : amphithéatre Bloch - Orme des Merisiers (CEA, accès libre)

      Notes de dernières minutes : Accès amphithéatre : http://iramis.cea.fr/spec/Contact/visitAmphiBloch.php

      Article

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