Eukaryotic cells contain extensive internal membranes defining many compartments having each specific functions. However these organelles are constantly moving and reshaping, still retaining their identity. The maintenance of cell compartmentalization in eukaryotes is thus very complex and tightly controlled. Nathalie Sauvonnet’s team deals with intracellular trafficking of eukaryotic cells and how it regulates cell and tissue organization. In particular we study endocytosis and exocytosis pathways and their linked to lipid distribution, cell compartmentalization and host-pathogen interactions. For this purpose we used an array of techniques from high resolution microscopy, single molecules tracking, robust image analysis, statistical classification, crispR-cas9 edition to organ-on-a-chip.
Our research focuses on the control of cell migration in health and disease. Cell migration is essential during development as well as in adult as it contributes to immune responses, tissue renewal, wound healing. In addition, cell migration and invasion is characteristic of highly malignant tumours that spread into the surrounding tissue to eventually metastasize 21,22. Migrating isolated cells but also migrating groups, sheets or chains of cells have been observed during physiological and pathological situations. Initiation of migration first requires cell polarization along a front to rear axis. Extracellular cues guiding polarization and migration include soluble factors such as chemoattractants and repellant as well as biochemical and biophysical properties of the extracellular matrix and of surrounding cells. These extracellular signals are transduced in intracellular signaling pathways that involve evolutionary conserved polarity proteins. The process of migration relies on the coordinated regulation of different cytoskeletal elements including actin, microtubule and intermediate filaments. This regulation occurs downstream of the polarity proteins to insure that the cytoskeletal networks organized in a polarized manner.
The Lymphocyte Cell Biology Unit investigates early stages of the adaptive immune response, in particular the molecular mechanisms that lead to the generation and function of immunological synapses, and their subversion by the lymphotropic retroviruses HIV-1 and HTLV-1.
The infection of an organism by a pathogen (e.g. virus or bacteria) triggers a specific and long lasting immune response, called the adaptive immune response that allows the defense of the organism. T lymphocytes are in the center of adaptive immune responses, since they contribute to their regulation and to the destruction of infected or cancer cells.
T lymphocytes are activated when they detect on the surface of antigen presenting cells the presence of molecular fragments (antigens) derived from pathogens. When a T cell recognizes its specific antigen, it polarizes towards the antigen-presenting cell, generating an organized cell-cell contact named the immunological synapse. Immunological synapses are multitask interfaces that allow the triggering and control of T cell activation, leading to proliferation and differentiation. They also enable T cell effector functions, like polarized secretion of cytokines and of cytotoxic granules.
Our goal is to elucidate how immunological synapses are generated and control T cell functions. We investigate the role of receptors and intracellular signaling molecules, of the actin cytoskeleton and microtubules and of intracellular vesicle traffic, in the formation of immunological synapses and in T cell activation. We also study how retroviruses that infect T lymphocytes, such as the human immunodeficiency virus (HIV-1), or the human T cell leukemia virus (HTLV-1) subvert the mechanisms of generation of immunological synapses in order to modulate T cell responses and to better spread from cell to cell.