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  • Génomes

    • Vendredi 7 septembre 11:00-12:00 - Rami Hannoush - Department of Early Discovery Biochemistry, Genentech Inc, CA USA

      Pharmacological modulation of Wnt signaling in intestinal stem cells

      Résumé : The Frizzled (FZD) 7 receptor (FZD7) is enriched in LGR5+ intestinal stem cells and plays a critical role in their self-renewal. In general, FZD proteins interact with Wnt signaling proteins via, in part, a lipid-binding groove on the extracellular cysteine-rich domain (CRD) of the FZD receptor. This presentation will highlight our lab’s recent efforts in providing new structural insights into the molecular arrangement of members of the FZD receptor family and their mode of regulation by cis-unsaturated fatty acids. We also highlight drug discovery approaches and structural bases for targeting specific FZD isoforms. In particular, we describe the identification of a potent peptide that selectively binds to the FZD7 CRD at a previously uncharacterized site and alters the conformation of the CRD and the architecture of its lipid-binding groove. Treatment with the FZD7-binding peptide impaired Wnt signaling in cultured cells and stem cell function in intestinal organoids.
      Contact : GIGLIONE Carmela <carmela.giglione i2bc.paris-saclay.fr>

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

      Article

    • Lundi 10 septembre 11:00-12:00 - Sander Granneman - Centre for Synthetic and Systems Biology (SynthSys) University of Edinburgh

      Post-transcriptional regulation of adaptive responses in microorganisms

      Résumé : Work in my lab is focusing on understanding how microorganisms manage to rapidly adapt (and even thrive) to sudden changes in their environment. Many pathogenic species have developed very sophisticated mechanisms to efficiently scavenge essential nutrients from the host environment and even evade the immune system.
      We hypothesize that this successful rapid adaptation program is underpinned by the ability of the microorganism to very rapidly remodel its gene expression profile.
      Obviously, transcription factors largely dictate which genes are switched on and off during adaptive responses. However, it is becoming increasingly clear that post-transcriptional regulation plays a key role in this process by shaping gene expression profiles. Small non-coding RNAs (sRNAs) and RNA-binding proteins (RBPs) are believed to play a crucial role in post-transcriptional regulation by modulating the translation efficiency and stability of mRNA targets. However, for the vast majority their function is unknown, underscoring the need for a thorough analysis of these molecules.
      Over the years my group has developed a number of powerful high-throughput methods that enable us to unravel post-transcriptional regulatory networks controlled by non-coding RNAs and RBPs. Our initial studies in yeast uncovered a novel role for RBPs in co-transcriptionally controlling the expression kinetics of stress-responsive genes as well as targets for thousands of bacterial sRNAs. We are currently expanding our research into pathogenic bacteria. Collectively, our data provide intriguing insights into how non-coding RNAs and RBPs are employed to fine-tune gene expression in response to stress. Results from these studies will be presented.
      Contact : ROUGEMAILLE Mathieu <Mathieu.ROUGEMAILLE i2bc.paris-saclay.fr>

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

      Notes de dernières minutes : Demo of the Vari-X-linker will follow (14h ) at CEA Saclay (building 144). Contact Mathieu for participation. Be careful CEA requires authorization to enter the campus

      Article

    • Vendredi 14 septembre 11:00-12:00 - Hironori Niki - National Institute for Genetics (NIG), Japan

      A long-periodical expression of trj1, a key gene responsible for fungal temperature response, in the dimorphic fission yeast Schizosaccharomyces japonicas

      Résumé : Many fungi respond to environmental cues including light and temperature in order to regulate fungal development and behavior. The WC proteins are assembled in a white collar complex (WCC) that is the major transcription factor of the light response in fungi. Orthologs of the WC proteins are found in dimorphic fission yeast Schizosaccharomyces japonicus. Indeed, hyphae of Sz. japonicus show synchronous activation of cell division in response to light. Besides, thermal stimuli can induce the similar response under continuous darkness (Okamoto et al. 2013). When temperature cycles (30°C for 12 h and 35°C for 12 h) were applied, distinct dark- and bright-colored stripes of hyphae were formed on an agar plate. We identified a key gene for the temperature response in our knockout gene library of Sz. japonicus. The gene, trj1, encodes a 63 kDa protein including the BTB/POZ domain, which is involved in protein-protein interaction. Orthologs of trj1 are broadly conserved in the kingdom Fungus alone. We analyzed the expression of tri1 after the temperature stimuli. Interestingly, tri1 showed a long-period change in the gene expression. After temperature shift-up, transcription started to increase mRNA of trj1, reached a maximum level after 18 h, and finally got back after 36 h. The regular expression patterns of trj1 were observed between 25°C and 35°C, suggesting the regular expression is temperature-compensated. Although the gene expression changed for over a day, the regular expression pattern of trj1 oscillated with 24 hours period during the temperature cycles. Both light and temperature, which are daily external cues, have the same effect on growing hyphal cells in Sz. japonicus. The dual sensing mechanism of external signals allows the organism to adapt to daily changes of environmental alteration.
      Contact : Yoshiharu YAMAICHI <Yoshiharu.YAMAICHI i2bc.paris-saclay.fr>

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

      Article

    • Lundi 24 septembre 11:00-12:00 - Jade Wang - Department of Bacteriology, University of Wisconsin at Madison, USA

      Spontaneous Mutations and Phenotypic Switches in the Bacterium Bacillus subtilis

      Résumé : The ability to generate diversity within a clonal population is important for organisms to survive later onset of selective pressures. For example, in bacteria, antibiotic resistance can arise via spontaneous mutagenesis, which is an example of a genotypic switch, and antibiotic tolerance can arise via persister formation, which is an example of a phenotypic switch. Characterization of both processes is challenged by the difficulty of detecting switched cells, which are rare events, within a large population.
      In this lecture, I will discuss ongoing efforts in my lab to characterize these two processes
      Contact : Frédéric BOCCARD <Frederic.BOCCARD i2bc.paris-saclay.fr>

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

      Article

    • Vendredi 28 septembre 11:00-12:00 - Joana Santos - Institute of Pharmacology and Structural Biology (IBPS), Toulouse

      How malaria parasites commit : a tale of transcription factors and epigenetics

      Résumé : Malaria, a disease that infects 3% of the world population and kills half a million people each year, is caused by the parasite Plasmodium. The disease symptoms are correlated with exponentially increasing waves of red blood cell (RBC) invasion and egress, in which parasite forms called schizonts rupture and release merozoites fit for a new round of RBC invasion. Alternatively, some schizonts (<10% of the population) enter the sexual pathway and differentiate into male and female gametocytes. While morphologically identical, sexually committed- and asexually committed-schizonts are transcriptionally programmed to either generate merozoites that invade RBCs, replicate and originate new merozoites, or that instead differentiate into gametocytes. Both ways are indispensable for parasite survival - Plasmodium must invade in order to subsist because it is an obligatory intracellular parasite, and gametocytes assure host-host transmission because they are the only parasite forms that can be uptake during a mosquito bite. How schizonts commit to each pathway remains a mystery.
      The Plasmodium genome is organized similarly to other eukaryotes and gene expression is regulated by binding of transcription factors (TFs) to promoter regions upstream of gene bodies. The ApiAP2 is the only characterized family of TFs in Plasmodium. I have characterized an essential ApiAP2 TF, named AP2-I, that regulates expression of the majority of invasion genes by binding to their promoters and recruiting a bromodomain protein (BDP1). Intriguingly, several lines of evidence suggest that AP2-I and BDP1 are not only involved in programming parasites to invade RBCs, but may also program parasites to enter the sexual development program. If this model were proven correct, these would be the first protein factors involved in schizont commitment.
      I propose to use different genomic and molecular approaches at the population and single cell level, including Cas9- and Cas13-derived methods as well as real time imaging, to identify the transcription regulation mechanisms involved in parasite commitment to the asexual and sexual pathways.
      Contact : Mireille Betermier <mireille.betermier i2bc.paris-saclay.fr>

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

      Article

  • cytoskeleton club

    • Mardi 11 septembre 11:30-13:00 - Valérie Campanacci - MiKiCa - B3S

      Cytoskeleton club

      Résumé : Selection and characterization of artificial proteins targeting the tubulin α subunit

      Lieu : Bibliothèque - bât. 34

      Article

Soutenance

  • Génomes

    • Lundi 10 septembre 14:00-17:00 - Wenfeng LIU - Signalisation et Réseaux de Régulations Bactériens

      ARN régulateurs et adaptation aux antibiotiques chez Staphylococcus aureus

      Résumé : Staphylococcus aureus est un agent pathogène opportuniste responsable d’infections communautaires et nosocomiales pour lesquelles les traitements sont compliquées du fait de l’émergence de souches multi-résistantes. L’adaptation rapide de S. aureus à de multiples conditions de croissance contribue à sa virulence ; elle dépend de nombreux facteurs incluant la régulation des petits ARN (ARNrég). Nous avons réalisé une étude précise de tous les petits ARN de la souche modèle HG003, un dérivé de la souche NCTC8325 couramment utilisé pour les études de régulation génétique chez S. aureus. C’est une tâche complexe qui est essentielle pour réaliser des études moléculaires et fonctionnelles. Nous avons trouvé environ 50 authentiques (bona fide) petits ARN, un nombre beaucoup plus faible que précédemment rapporté. Comme la plupart des ARNrég contribuent à une « régulation fine » de l’expression génique, les phénotypes dépendants des ARNrég sont généralement difficiles à détecter. Cependant, ces phénotypes peuvent apparaître comme un caractère important après plusieurs générations sous une pression sélective. Nous avons développé une stratégie expérimentale pour mesurer l’évolution de la quantité de mutants d’ARNrég dans une population de mutants de S. aureus. Nous avons construit une collection de quatre-vingts mutants d’ARNrég dans la souche HG003. Chaque gène d’ARNrég est remplacé par une séquence d’ADN « code-barres » spécifique pour l’identification des mutants. La bibliothèque de mutants est cultivée dans différentes conditions de croissance, les codes-barres sont amplifiés par PCR et comptés par séquençage massif. Nous pouvons ainsi déterminer les mutants qui diminuent ou s’accumulent pendant une condition de stress et inférer une fonction à certains ARNrég. L’utilisation d’amorces spécifiques permet de multiplexer 50 conditions expérimentales. Nous nous sommes posés la question suivante : les ARNrég de S. aureus participent-t-ils à la résistance aux antibiotiques ? Dans ce mémoire, nous présentons des données en utilisant la méthode décrite ci-dessus. La bibliothèque de mutants d’ARNrég a été testée en présence de 10 antibiotiques ciblant les enveloppes, la synthèse des protéines, la réplication de l’ADN ou la synthèse de l’ARN. Plusieurs mutants sont affectés par les conditions de croissance testées. Par exemple, la proportion du mutant sau6836 augmente considérablement en présence de vancomycine et est réduite en présence de flucloxacilline, cloxacilline ou céfazoline. La proportion du mutant ARNIII-agr augmente progressivement en présence de gentamicine, de linézolide et de clindamycine. La proportion de mutant d’ARN 6S diminue significativement en présence de rifampicine. Il est important de noter que l’ARN 6S et la rifampicine ciblent l’ARN polymérase. L’ARNrég RsaA est un régulateur des autolysines dont l’absence affecte la survie en présence de ciprofloxacine. Ces exemples illustrent la puissance des expériences de compétition pour identifier les phénotypes dépendants des ARNrég et révèlent que plusieurs ARNrég contribuent à moduler la résistance aux antibiotiques.

      Lieu : Salle A. Kalogeropoulos, Bat400 - Campus Université Paris-Sud

      Article

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