Project 170476

Embedded in the membranes of all living cells, membrane proteins are the molecular links between the inside and outside world. These proteins help preserve the biological structure of the cells; they act as receptors by participating in signaling (such as telling the cell when to 'grow'); and they act as transporters to regulate the flow of molecules into and out of the cell, including calcium or sodium ions, nutrients such as amino acids and sugars, as well as drugs and more complex molecules. Membrane proteins consist of long chains of amino acids; critical mutations even at a single point in the chain underlie the causes of many human diseases. These include several forms of cancer, diabetes, and cystic fibrosis. But it is very difficult to deduce the molecular mechanisms of a disease, and move toward drug design/therapy, without fundamental structural information about the overall protein. Our research involves studies of proteins and peptides, focusing on the protein segments that are physically integrated into the cell membranes. By using a variety of modern laboratory methods and instruments that can be applied to the determination of protein structure, we hope to discover how small variations in the amino acid sequence impact on the ability of the protein to function normally. This research should yield fundamental information as to how specific amino acids within membranes give rise to the correct protein function, and in the longer range will provide the rationale for ascribing a structural basis to the aberrant effects of disease-related mutations in membrane proteins. As we increase our understanding of these important molecules, we will be better positioned to develop therapies against diseases of these proteins.

using a variety of modern laboratory methods and instruments to determine the structure of membrane proteins and understand the impact of amino acid sequence variations on protein function