Research Interests

Clathrin-mediated endocytosis allows cells to capture nutrients and other important molecules by engulfing them in a capsule made from the plasma membrane. This is a vital process that contributes not only to nutrient uptake but to other cellular functions including recycling of synaptic vesicles in the brain, communication within and between cells and development of cells and tissues to perform specialised functions. In addition the endocytic apparatus is used by some viruses (notably HIV and influenza) and bacteria to gain entry into cells and there is accumulating evidence that endocytic proteins are associated with a wide range of diseases including neurodegenerative disease and cancer.

Clathrin-mediated endocytosis operates through formation of a vesicle from the cell's membrane trapping cargo molecules inside. This process is controlled by a network of proteins which include clathrin and a set of adaptor proteins which bind to clathrin. Clathrin assembles to form a polyhedral cage which, together with its adaptor proteins, forms a coat around the vesicle. The vesicles then detach from the membrane and move to a location inside the cell to deliver their contents. It remains a mystery how so many different adaptor proteins coordinate with a single protein so that this cellular postal system can achieve its function.

We aim to solve this mystery using two main approaches. First, by using electron microscopy images of frozen protein mixtures we can determine three-dimensional maps that show what these proteins look like and how clathrin’s adaptor protein binding partners are arranged within a cage structure. Secondly, by using advanced biophysical techniques we can measure how these adaptor proteins bind to clathrin and how clathrin cage assembly and disassembly is controlled. In this way we hope determine how clathrin coats specify and are involved in so many critical functions in cells.

Scientific Inspiration

My scientific inspiration comes from the pioneering ethos of the lab in which I did my own PhD, summed up by the ambition to identify the key, ‘killer’ experiment and use enterprise, imagination and courage in equal measure to carry it out.