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Research in my laboratory focuses on the molecular cell biology and signal transduction of phagocytosis in mammalian cells, with particular emphasis on the initial steps of uptake, from particle recognition to phagosome closure. Phagocytosis is emerging as a phylogenetically conserved process, that is regulated by both actin and membrane dynamics and also targeted by numerous bacterial toxins and virulence factors. From a cellular and molecular perspective, phagocytic uptake is akin to adhesion and motility, using similar types of adhesion molecules, cellular mechanisms (actin polymerisation, focal exocytosis) and signalling pathways (eg controlled by small G proteins like Rho-family members and Arf6). Specifically, we are trying to decipher the signalling pathways directing internalisation through the two main phagocytic receptors normally expressed in professional phagocytes (macrophages and neutrophils): complement receptor 3 (CR3, a beta2 integrin) and Fc gamma Receptors (FcgR). These surface receptors control uptake of inert particles, bacteria and apoptotic cells in health and disease. Thereby, we are seeking to get a better understanding of 1/ how local signalling at the plasma membrane is coordinated with other phagocyte responses, such as cytokine production; 2/ how microbial pathogens interfere with phagocytosis signalling; 3/ the molecular mechanisms underlying CR3 and FcgR function, including the identification of new regulators of phagocytic uptake.
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