My research group studies the chemistry that happens inside living organisms, in particular how cells modify proteins. We design and apply new chemical approaches with a focus on the biology of disease, which may lead to the discovery and validation of novel drug targets and initiation of drug discovery programmes.
Proteins are the machines that run cells and all life, converting chemical energy into motion, electrical activity or thought, and defending the body from infections. Chemical modification of proteins, or 'post-translational modification' (PTM), can be thought of as adding an ‘upgrade’ to a protein machine to allow it to work in a new or more efficient way.
For example, the modification might ensure it is in the right place at the right time to do its job effectively, or allow it to respond in time to a critical event.
PTMs are themselves added by other proteins (enzymes) and are also used by organisms that cause disease such as malaria parasites, or viruses which can commandeer our cells' enzymes to modify their own proteins. For example, PTMs allow assembly of the protective protein shell which allows them to infect new cells. Cancer cells also switch off PTMs, or even add new ones, to evolve resistance to the body’s immune response or to drugs.
In my lab we have developed new chemical technologies to understand how PTMs work across whole cells or organisms, and we are particularly interested in identifying ways to disable or enhance protein modification to target diseases.
For example, we have developed new potential therapeutic approaches for the treatment of diseases as diverse as malaria, cancer and the common cold, by focusing on understanding and manipulating the chemistry of protein modification.
We work closely with other groups at the Crick, including the Downward, Calado and Carvalho labs and STPs such as Chemical Biology and High Throughput Screening, and with my group at Imperial College London. For example, our collaboration with Dinis Calado led to the first Crick/Imperial joint spinout company, Myricx Pharma, which is working to deliver our findings into the clinic to benefit patients.