Lipids are the main component of cellular membranes; however, they can also act as key signalling molecules. Vital to almost all signalling pathways is the production of lipid signals, with specific lipids known as phosphoinositides mediating many key signaling roles. Different phosphoinositides act as a code for the recruitment of downstream signalling proteins to specific intracellular membranes. Lipid phosphoinositides play fundamental roles in virtually all pathways that control a cell’s decision to grow, move, divide, and die. Because of this, the kinases that phosphorylate phosphoinositide lipids are involved in myriad essential cellular functions. The misregulation of phosphoinositide kinases is critical in human diseases, including cancer, primary immunodeficiencies, viral infection, malaria, and inflammation.

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There are still major knowledge gaps in how lipid signalling enzymes are regulated in health and disease. The main overarching goal of my research is to understand the molecular mechanisms of how lipid signalling enzymes are regulated, with a particular focus on phosphoinositide kinases, and how they are involved in numerous diseases. This misregulation frequently manifests itself in diseases through the inappropriate activity of these proteins. Specific examples include the phosphoinositide 3 kinases, which are one of the most frequently mutated enzymes in human cancer.

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The two signalling systems we are interrogating is the PI3K and PI4K family of PI kinases, and their involvement in cancer, primary immunodeficiencies, developmental disorders, viral infection, and malaria.