Ben Nichols

The plasma membrane provides the key interface between a cell and its environment, and thus has a central role in a very wide range of cell processes. We are interested in the mechanisms underlying several important aspects of plasma membrane cell biology: particularly, how regions of the membrane are specialised for different functions, and how proteins and lipids are internalised from the membrane. We focus on the role of oligomeric protein assemblies that form specific microdomains. Caveolae, flask-shaped membrane invaginations formed by cavin and caveolin proteins, constitute one kind of microdomain, and flotillin proteins form another. Achievements over the last 5 years have included revealing functions for flotillin proteins in cell migration, determining key protein actors at the neck of caveolae, characterising the large 80S protein complex that generates the bulb of caveolae, and quantifying flux through different endocytic pathways in tissue culture cells.

Studies in cultured cells and model organisms have been successful in identifying many molecular components and specific protein-protein interactions. We now want to confront the complexity of how these components function in differentiated cell types. Our interests in caveolae and in endocytosis lead to projected experiments to elucidate the function of caveolae in the vascular system, and the membrane traffic mechanisms underlying vesicular transcytosis in endothelium. We will complement these experiments with biochemical and functional analysis of protein complexes at the neck of caveolae. In the case of flotillins, we now know that these proteins have an important role in sphingosine-1-phosphate signalling, and projected experiments will determine both the relevant mechanisms and links to regulation of endocytosis.