Structural cell biology of transport vesicle and organelle biogenesis

Every one of the trillions of cells in the human body are surrounded by a lipid membrane and contain membrane-bound compartments. Proteins embedded in these membranes mediate cell interactions with the blood and the immune system. They also permit signals and small molecules to cross these membrane barriers. These embedded proteins are moved in the right quantities at the right times to the right membranes in transport vesicles. These are formed when a portion of a donor membrane, into which the correct embedded proteins have been sorted, is pinched off, transported to and fused with its target membrane. Failures in vesicle transport can result in cell death or malfunction leading to diseases including Alzheimer’s, Parkinson’s and cancer. The transport vesicle system can be ‘hijacked’ by pathogens to facilitate their entry into host cells.

We aim to determine, at atomic resolution, the structures of various protein nano-machines that are recruited onto membranes from inside the cell to drive a transport vesicle’s formation, transport and fusion.

Our findings will allow us to explain how these proteins function correctly and how they can go wrong. It will also allow us to design highly specific mutant forms to help test theories of vesicle formation/destruction in cells.