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How Membrane Physical Properties and Cortical Actin Regulate Protein Interactions During T Cell Signalling

Final Report Summary - MEMREGPRO (How Membrane Physical Properties and Cortical Actin Regulate Protein Interactions During T Cell Signalling)

The project generated a suite of new statistical analysis and software tools to quantify the nanoscale organisation of molecules within cells. These methods include describing clusters of proteins (number of clusters, number of molecules per cluster etc) as well as describing proteins which form bibrous patterns (mesh density, mesh regularity and so on). These tools were then used to describe the arrangement of key signalling molecules in T cells, the activation of which must be tightly regulated to ensure a corrent immune response. In particular, we discovered an increase in the clustering of ZAP-70 after activation and generated a detailes description of the arrangement of the cell skeleton. Unexpectedly, while examining the negative regulator of T cell activity PTPN22, we found that a loss-of-function mutation causes a failure of this protein to correctly decluster. This is potentially important as the same mutation has been found to predispose humans and mine to autoimmune diseases including arthritis and diabetes. Controlling nanoscale organisation of proteins therefore might have important implications for health and disease.