The clearance of dying cells is the last phase of apoptosis in vivo. Corpse removal prevents inflammation and autoimmunity. We plan to develop therapeutic strategies aimed to restore in vivo clearance, in order to prevent tissue damage and chronic inflammation. To this aim we will characterise the molecular machinery involved, using complementary approaches (from genetic screening in C. elegans to function complementation in autoimmune patient phagocytes). We will establish a panel of clearance defective animals bearing combined modifications of relevant genes and study the consequences of accumulation of apoptotic cells in selected tissues on the homeostasis of the organism. We will characterise the effect of molecular interventions in vivo in models of acute and chronic tissue inflammation. Finally we will exploit this system to identify novel autoantigens in vivo, which will be validated as diagnostic tools in patients with systemic autoimmune diseases.
Funding SchemeCSC - Cost-sharing contracts
EH1 1HN Edinburgh