Grants and Contributions:

Grant or Award spanning more than one fiscal year. (2017-2018 to 2022-2023)

Phagocytosis is the process by which cells internalize large particulate materials (senescent cells, microbes) from their milieu and sequester them in phagosomes. These newly formed phagosomes rapidly mature into phagolysosomes where the internalized material is degraded. This process plays a role in a wide range of cell functions, ranging from nutrition in ameba to innate and adaptive immunity in mammals. Hence, phagolysosomes play a central role in host defence through the destruction of microbes and by allowing the presentation of microbial antigens to the immune system. Our research program is aimed at understanding the role(s) of protein tyrosine phosphatases (PTPs) in the biogenesis and function of phagolysosomes, a model organelle. Phagolysosome biogenesis requires the coordinated action of multiple signaling molecules, including protein kinases, which regulate the interactions between the phagosome and the cytoskeleton, as well as the early, late and recycling endocytic compartments. The importance of tyrosine (Tyr) phosphorylation in phagosome signaling was evidenced by the finding that Tyr phosphorylation sites are overrepresented in the phagosome proteome, as compared to global phosphoproteome. Precise control of protein tyrosine phosphorylation is crucial for cellular homeostasis, and is achieved by the balanced action of protein tyrosine kinases and PTPs.

There is growing knowledge on the role of macrophage PTPs and their proteins targets in the regulation of phagolysosome biogenesis and function. We expect that our research program will contribute further to our understanding of the role of Tyr phosphorylation in these processes. Better knowledge of the PTPs and their targets involved in phagolysosome biogenesis may also provide a better understanding of microbial pathogenesis.