We are interested in understanding how various signalling proteins function, how they interact with other signalling molecules and how they can be modulated. We use largely structural biology approaches and apply different biochemical, biophysical and structural techniques in our research to elucidate the molecular details of these processes both in vivo and in vitro.
One of the system we have studied in detail is the extracellular regulation of TGFβ family growth factors. This is a large family of related proteins with over thirty members in humans and we are interested in the determinants of signalling specificity and interactions with inhibitor proteins and receptors. Our recent focus has been in elucidation of the details of the precursor forms of these growth factors, activin and myostatin in particular. Many of our projects are in collaboration with developmental and stem cell biologists and we run a core facility for the production of growth factors for local stem cell research groups.
We are members of an interdisplinary research consortium in Cambridge applying novel methods to the development of inhibitors against clinically relevant targets. Our particular aim is to inhibit these proteins outside the active site with particular focus on regulatory protein-protein interactions. These are traditionally seen as very difficult targets for chemical intervention but hold great promise for therapeutic use and as chemical tools. Together with groups of, Tom Blundell here in Biochemistry and Chris Abell and David Spring in the Department of Chemistry we have used various different approaches, often starting with small fragments (fragment-based drug discovery), but also using high-throughput hits as starting points and developed peptidomimetics. In these inhibitor development projects we employ calorimetry, X-ray crystallography and protein engineering amongst other techniques to guide the development process.
We are also active in translating our research to applications. We operate a core facility for production of growth factors for University of Cambridge Stem Cell Institute. That has also resulted in a spin-out company Qkine that will develop next generation growth factors for stem cell research and regenerative medicine appliations.