Mechanism and regulation of perforin function

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Perforin is a cytolytic protein found in cytotoxic lymphocytes. It plays an essential role in the destruction of virus- and pathogen- infected cells as well as tumour cells. Perforin deficiency in humans and experimental animals results in the loss of resistance to many viral infections and dramatically increases the chance of spontaneous tumour formation. Whilst perforin was first characterised two decades ago, its mechanisms of action remain unknown. The current Grant Proposal will capitalise on some recent key technological advances in our laboratory that are enabling us to investigate the mechanisms and the regulation of perforin function. Our recent advances in the field put us in a pre-eminent international position to conduct these studies. In broader terms, the proposed studies will have an immediate impact on our understanding of the mechanisms of cytotoxic lymphocyte regulated immune response and on immune homoeostasis in general. It will also improve our understanding of defence mechanisms against various pathogens and will provide more insight into the role of immune system in protection of the organism against cancer.