Our research programme aims at establishing mechanisms of regulation of an ancient family of giant kinases involved in cellular homeostasis. In addition, members of the family have important roles in human cancers. Projects include understanding mechanisms of regulation of the lipid kinase VPS34 and the protein kinases ATM and mTOR. VPS34 and mTOR are present in large complexes that are activated at membrane interfaces, and they are essential responding to nutritional stress. ATM is present in a large complex that enables it to assume a fundamental role in sensing and responding to DNA damage. We are characterising structural mechanisms regulation of these enzyme complexes as well as developing small molecule modulators of them.

Projects involve single-particle electron cryo-microscopy (cryo-EM) and cryo-electron tomography (cryo-ET), as well as characterisation of the dynamics of complexes by hydrogen/deuterium exchange mass spectrometry (HDX-MS), molecular dynamics and enzyme kinetics.