We are interested in understanding the proteins that regulate cellular signalling via post-translational modifications. Detailed understanding of these proteins enables the discovery of small molecule inhibitors which can then be used to probe the functions of the proteins and uncover new targets for treating disease.
Key proteins of interest in our research are those that catalyse post-translational modifications such as phosphorylation or ADP-ribosylation. Phosphorylation is catalysed by protein kinases; there are over 500 protein kinases in the human genome and most of them remain poorly characterized despite their importance regulating physiology. Our approach is to use high resolution structural information for the generation of selective inhibitors (chemical probes) which we use to gain understanding of the functions of these largely uncharacterized proteins. Our lab generated a large repository of efficient expression systems, recombinant proteins and crystal structures that now enables family wide structural comparison and screening. ADP-ribosylation is important in numerous cellular processes; as well as a well-established role in DNA damage detection and repair it is also important for host-virus interactions, epigenetic regulation and metabolism. We also have interests in lipid kinases and sphingolipid biosynthesis, which both have strong links to inflammation and cancer, and where mutations in the various proteins involved are associated with a variety of rare diseases.