We aim to understand the proteins that transmit signals within the cell and the signalling pathways that regulate the cell’s functions. Understanding these pathways and proteins enables the discovery of new drug 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 in regulating physiology. Furthermore, ADP-ribosylation is important in numerous cellular processes such as DNA damage detection and repair as well as metabolism, host-virus interactions and epigenetic regulation. Our approach is to use high resolution structural information for the generation of selective inhibitors (i.e. chemical probes) which we use to gain an understanding of the different functions of kinase proteins. We have therefore generated a large repository of efficient expression systems, recombinant proteins and crystal structures that enable family-wide structural comparison and screening.
In addition to our work on kinases, we have interests in lipid kinases and sphingolipid biosynthesis—both of which have strong links to inflammation and cancer—and where mutations in the proteins involved are associated with a variety of rare diseases.