Grant: Project Grant

White blood cells of the innate immune system protect the body against invading microorganisms and also clear the remnants of the ~2 billion dead cells within our body each day. These white cells have the unique ability to engulf and destroy the microorganisms and effete cells. The engulfment process, known as phagocytosis, is initiated by specialized proteins on the cell surface, called receptors, which detect the potential pathogens or dead cells and facilitate their uptake. Once internalized, the 'prey' is degraded inside vacuoles (phagosomes) by digestive enzymes delivered by a process called maturation. To avoid infections and autoimmune disorders, it is important to understand the mechanisms underlying the internalization and maturation of phagosomes. Curiously, the maturing phagosome is not an inert vacuole but a highly dynamic organelle that interacts with other organelles and ultimately, breaks down once the prey is degraded. The proposed research has three main objectives. 1) Understand the importance of contacts between the forming phagosome and the endoplasmic reticulum (a large, mesh-like organelle) in regulating signaling. 2) Define the stages of the phagosomal maturation process and the subsequent breakdown into lysosomes (degradative organelles that act as the cell's stomach) and 3) Determine how macrophage prevent an unhealthy buildup of cholesterol while eating dead cells.