Nos tutelles


Nos partenaires


28 septembre 2018: 1 événement

  • Département Biologie des Génomes

    Vendredi 28 septembre 2018 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>

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

    En savoir plus : Département Biologie des Génomes