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Les événements du mois


  • Génomes

    • Friday 8 September 11:00-12:00 - Dr Diarmaid Hughes - Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden

      Evolutionary trajectories to ciprofloxacin-resistance in Escherichia coli

      Résumé : Ciprofloxacin is an important antibacterial drug targeting Type II topoisomerases, and is highly active against Gram-negatives including Escherichia coli. The evolution of resistance to ciprofloxacin in E. coli always requires multiple genetic changes, usually including mutations affecting two different drug target genes, gyrA and parC, but frequently also involving mutations in drug-efflux regulators. Resistant mutants selected in vitro or in vivo can have many different mutations in target genes and efflux regulator genes that contribute to resistance. However, among resistant clinical isolates there are a few predominant genotypes, suggesting they have a selective advantage. By combining experimental data and mathematical modeling, we mapped the fitness landscape that constrains the evolutionary trajectories taken during the development of clinical resistance and could explain the predominance of the most frequently selected genotypes.
      Contact : Nara Figueroa

      Lieu : Auditorium - Bâtiment 21, campus de Gif


  • Biologie Cellulaire

    • Friday 22 September 11:00-12:30 - Vesa Markus OLKKONEN - Minerva Foundation Institute for Medical Research, Helsingfors, Finlande, invité par Francesca Giordano

      OSBP-related protein 2 (ORP2): A new regulatory node between cellular energy metabolism, adhesion, migration and proliferation

      Résumé : ORP2 is a ubiquitously expressed OSBP-related protein previously implicated in triacylglycerol (TG) metabolism at endoplasmic reticulum (ER) - lipid droplet (LD) contacts, cholesterol transport, and adrenocortical steroidogenesis. We now characterize the functional role of ORP2 by employing ORP2-knock-out (KO) hepatoma cells generated by CRISPR-Cas9 gene editing. Loss of ORP2 did not affect the major cellular phospholipids, cholesterol, or oxysterols, nor the quantity of ER-LD contact sites. However, the knock-out resulted in reduced expression of SREBP-1 target genes and mRNAs encoding glycolytic enzymes, defective TG synthesis and storage, inhibition of LD growth upon fatty acid loading, reduction of glucose uptake, glycogen synthesis, glycolysis (ECAR) and Akt activity. ORP2 was found to form a physical complex with key controllers of Akt, Cdc37 and Hsp90. In addition to the metabolic phenotypes, the ORP2-KO cells showed defects in adhesion, lamellipodieae formation, migration and proliferation, and the ORP2 interactome contained, in addition to Cdc37, a number of actin regulatory components. The putative lipid transport steps that ORP2 function may involve are as yet unknown, albeit we find a sterol-PI4P countertransport function quite possible.
      To conclude, the present study identifies ORP2 as new regulatory node between cellular energy metabolism, adhesion, migration and proliferation.

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


  • Microbiologie

    • Tuesday 12 September 12:45-13:45 - Dr Marcia ORTEGA RAMOS - Dept. of Biochemistry & Molecular Biology, The Pennsylvania State University University Park, Etats-Unis

      Towards Assembly of a Type I Reaction Center in a Purple Phototroph

      Résumé : Engineering photosynthetic bacteria to utilize a heterologous reaction center (RC) containing a different photo-pigment could improve solar energy conversion efficiency by allowing the cell to absorb a broader range of the solar spectrum. One promising candidate is the homodimeric Type I RC from Heliobacterium modesticaldum (HbRC). It is the simplest known RC and has the benefit of using Bchl g, which absorbs in the near-infrared region of the spectrum. The purple phototrophic bacterium Rhodobacter (Rba.) sphaeroides was chosen as the platform into which the HbRC is introduced. However, to assemble a functional HbRC, engineered production of bacteriochlorophyll g (BChl g), must first be achieved. BChl g and BChl b are two chlorophyll (Chl) derivatives that contain an ethylidene substituent on ring B and share very similar biosynthetic pathways. Using the background strain Rba. sphaeroides producing BChl b rather than the native BChl a, we were able to re-direct the biosynthesis of pigments to produce an analog of BChl g. The majority of Chls and BChls found in nature contain a C20 phytyl alcohol moiety, whereas BChl g contains a shorter C15 farnesyl tail. To ensure that the BChl g produced in Rba. sphaeroides can be correctly incorporated into a heterologous HbRC, we are redirecting the native terpenoid pathway to produce these shorter alcohol moieties. By combining both strategies we may be able to generate a functional HbRC in Rba. sphaeroides. Ultimately this mutant will be used as the platform in which the HbRC will be assembled. This strategy could be applicable to other organisms, such as cyanobacteria, thereby expanding the range of the solar spectrum they are able to absorb.
      Invitée par l’équipe "Biologie et Biotechnologie des Cyanobactéries"

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


    • Thursday 14 September 15:00-16:00 - Dr Christophe CORRE - Life Sciences & Chemistry University of Warwick United Kingdom

      Mining bacterial transcriptional regulators for the discovery of natural products, biocatalysts and synthetic biology tools

      Résumé : Invité par l’équipe "Microbiologie Moléculaire des Actinomycètes"

      Lieu : Salle A. Kalogeropoulos - Bâtiment 400, campus d’Orsay


  • B3S

    • Thursday 21 September 15:30-16:30 - Pr Shunichi Takeda - Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Kyoto, Japan

      The role Mre11-Rad50-Nbs1 complex in double-strand-break repair – Myth and Facts

      Résumé : Homologous recombination initiates double-strand break (DSB) repair by digesting 5’-termini at DSBs, the biochemical reaction called DSB resection, during which DSBs are processed by nucleases to generate 3’ single-strand DNA. Rad51 recombinase polymerizes along resected DNA, and resulting Rad51-DNA complex undergoes homology search. Although DSB resection by the Mre11 nuclease plays a critical role in HR in Saccharomyces cerevisiae, it remains elusive whether DSB resection by Mre11 significantly contributes to HR-dependent DSB repair in mammalian cells. Depletion of Mre11 decreases the efficiency of DSB resection only by a few times in mammalian cells. We show that although Mre11 is required for efficient HR-dependent repair of ionizing-radiation-induced DSBs, Mre11 is largely dispensable for DSB resection in both chicken DT40 and human TK6 B cell lines. Moreover, 2- to 3-fold decrease in DSB resection has virtually no impact on the efficiency of HR. Thus, although a large number of literatures have reported the vital role of Mre11-mediated DSB resection in HR, the role may not explain the very severe defect in HR in Mre11-deficient cells including their lethality. We here show experimental evidences for the additional roles of Mre11 in (i) elimination of chemical adducts from DSB ends for subsequent DSB repair, and (ii) maintaining homologous recombination intermediates for their proper resolution.
      Contact : Jean-Baptiste Charbonnier

      Lieu : Salle de Conférences - Bâtiment 144, Campus de Saclay


  • cytoskeleton club

    • Tuesday 12 September 11:30-12:30 - Christophe Le Clainche

      Cytoskeleton Club

      Résumé : Understanding cellular force response through the in vitro reconstitution of mechanosensitive protein machineries

      Lieu : Bibliothèque - Bâtiment 34, campus de Gif



  • Microbiologie

    • Friday 15 September 14:00-17:00 - Jerzy Witwinowski - Département de Microbiologie, I2BC

      Biosynthèse de dicétopipérazines chez les actinobactéries

      Lieu : Salle Kalogeropoulos - Bâtiment 400, campus d’orsay


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