How do phagocytes control phagosome fate and pathogen killing?

Our goal is to understand how phagocytic cells control how they kill different microbes. This core role of immune cells is key to preventing infections, but how pathogen processing is controlled and especially how this adapts to different microbes remains a major gap in our knowledge. We previously identified key lipid signals required for phagosome maturation and pathogen killing. Using the unique tools we have developed, we now find this signalling is modulated in response to different microbes - defining a novel key feature of the innate immune response. Our aims are therefore to understand how this signalling is controlled, how it mediates phagosome processing, and how this helps immune cells adapt to different prey. This is a cell biology proposal, working across scales from biochemical reconstitution, cellular and whole-animal models, and primary human cells. The tools and methods we have developed put us in a unique position to investigate both the molecular mechanisms and physiological significance of phagosome processing. This will enable us to uncover core mechanisms of the innate immune response and fundamentally change our knowledge of how phagocytes respond to diverse microbial challenges. Keywords: Phagocytosis, trafficking, phosphatidylinositol, endocytosis, innate immunity