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Hijacking the Host : genomic and epigenomicaspects of host-parasite interaction

proposé par Professor Jonathan Weitzman, Université Paris Diderot

Projet de stage

We study how intracellular parasites change the phenotypes of their host cells. We use cellular and genomic approaches to investigate how pathogens hijack the signaling pathways of host cells to manipulate their genomes and epigenomes. We have been studying how Theileria parasites hijack host signaling pathways to induce host cell transformation. We identified epigenetic events in the host cell nucleus that are induced by the intracellular parasite. One example is the regulation of a positive feedback loop involving microRNAs (Marsolier et al., 2013) ; the parasite induces oncogene addiction which maintains host cell phenotypes. We also found examples of host methylation events induced by the parasite which lead to stable changes in host nuclear chromatin and gene expression (Cock-Rada et al. 2012). In addition to investigating changes in the host genome and cellular states, we explore unique features of the parasite genome. We mined the Theileria genome in search of parasite-encoded onco-proteins. We identified a parasite-encoded Pin1 protein that is secreted into the host cell and rewires host cell metabolism and oncogenic signaling (Marsolier et al., 2015). We study Theileria-infected leukocytes as a model to explore the plasticity of cellular phenotypes, the determinants of cell identities and the evolutionary strategies of interacting cellular systems. The M2 project will take an integrated genomic and proteomic approach to investigate parasite-induced transformation. The project is supported by funding from the ANR and the Labex WHO AM I ? The Unité Epigénétique et Destin Cellulaire is equipped with all the technologies and expertise necessary for successful completion of this project. The successful candidate should be curious about phenotypic plasticity and interdisciplinary approaches to epigenetic regulation. We are looking for a team player with creativity,passion and determination

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