Cell migration is essential for wound healing, immune and inflammatory responses, and tumour cell metastasis is dependent on cell migration. Our research aims to identify and characterise key signalling molecules involved in the migration of leukocytes, endothelial cells and epithelial cancer cells, which could be targets for therapeutic intervention in human diseases. We are focusing on signal transduction by the Rho family of GTPases, which we have shown play essential roles in cytoskeletal remodelling and changes in cell adhesion during cell migration. In humans there are 20 Rho GTPases, most of which are regulated by cycling between an active, GTP-bound conformation and an inactive GDP-bound conformation. We are using a combination of RNAi and expression of wildtype and mutant proteins to determine how Rho GTPases, their regulators and downstream target affect cell migration and invasion. Cell migration, invasion, and protein localisation are analysed by confocal and time-lapse microscopy. Biochemical techniques are used to investigate how signalling proteins are regulated and localized within migrating cells, for example by studying changes in protein-protein interactions and protein phosphorylation.

Cell migration and invasion in cancer and inflammation; Rho GTPases; signal transduction.

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