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10 septembre 2019: 3 événements

  • Département Biologie des Génomes

    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

    En savoir plus : Département Biologie des Génomes
  • Département 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.
    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

    En savoir plus : Département Biologie Cellulaire
  • Cytoskeleton club

    Mardi 10 septembre 11:30-12:30 -

    Cytoskeleton club - Internal seminar

    Lieu : Bibliothèque - bât. 34

    En savoir plus : Cytoskeleton club