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5 novembre 2018: 1 événement


    Lundi 5 novembre 14:00-15:00 - Alexandre GRASSART - Institut PASTEUR, Paris

    From single molecule to tissue : understanding endocytosis mechanisms at its native state

    Résumé : Cells permanently communicate with its environment and mediate information inside the cell through an intricate vesicular trafficking network. At the plasma membrane, receptor-mediated endocytosis is deeply integrated to this cellular logistic and thus play key role in the regulation of cell signaling and homeostasis. My research is focused on understanding the molecular mechanisms and regulatory circuit underlying the assembly of these cellular machineries. To do so, I pioneered an approach based of gene-editing in human cells, live-cell imaging with single molecule resolution and analytical tools to determine the native stoichiometry of proteins during endocytosis in real time. My findings support a model in which endocytosis pathways are governed by two decisional checkpoints. Now I aim to better identify the molecular factors involved in these critical steps and define the regulatory mechanisms involved. A particular effort will be focus on understanding how the physical and cellular microenvironment could interplay with the endocytosis molecular machinery dynamics and determine its impact on intestinal stem cell fate. Toward this goal, I recently developed a biomimetic device recapitulating a 3D organotypic intestinal epithelium barrier interface and the mechanical forces encountered at the organ level. During this presentation, I will present this approach and data demonstrating its physiological relevance. In particular, I tested the capacity of this new model system to recapitulate the infection of Shigella flexneri, an enteroinvasive bacterium whose natural reservoir is exclusively human. In contrast to conventional “flat” in vitro models, I could strikingly observed a level of infection close to clinical data. Thus, this strategy opens new avenues for studying in vitro the biology of human intestinal epithelial cell barrier and its interactions in an environment close to its physiological state.

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

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