Our group investigates the roles of phosphoinositide 3-kinase (PI3K) enzymes in immunity and infection. Cells of the immune system can express up to eight different PI3K isoforms, all of which have in common that they add a phosphate to the 3rd hydroxyl position of the inositol ring of phosphatidylinositols which form part of the cell membrane. These 3-phosphorylated phosphatidylinositols act as second messenger signalling molecules within cells that control diverse of cellular functions and genetic programmes. Our group tries to dissect the unique roles played by individual PI3K isoforms with particular focus on their roles in B cells and T cells. We also ask what the effect of inhibiting or enhancing the activity of individual PI3K isoforms has on immunity to infections.
Most of our work to date has focused on the p110δ isoform (sometime also referred to as PI3Kδ). P110δ is a so-called class IA PI3K because it becomes recruited to tyrosine-kinase linked receptors by one of several SH2 domain containing regulatory subunits called p85. The activation of p110δ is one of the first events that happen inside a T cell or B cell when it first is exposed to a foreign antigen. Because p110δ is expressed at very low levels in other organs in the body, it is thought that targeting p110δ with drugs may be an effective way to suppress immune responses without some of the the side effects associated with many immunosuppressive drugs in current use. We therefore work closely with colleagues in pharmaceutical companies who have developed specific inhibitors against p110δ or other PI3K isoforms to help predict and understand the effect of such drugs on the immune system.