Grant: Operating Grant - PA: Institute of Genetics (Bridge Funding)

Our study investigates the protein that is responsible for removal of acid from cells. As a byproduct of cell metabolism, acid is produced. Too much acid has deleterious effects on many cellular tissues including the heart. The protein that removes the acid from cells is called the Na+/H+ exchanger. This protein is found in the outside membrane of the cell. It is known to remove excess intracellular acid in exchanger for an outside sodium molecule. The protein is critically involved in heart disease, and helps regulate cell growth and movement. Several companies are now developing new drugs to inhibit the activity of this protein - which results in improved outcome in some types of heart disease. Our study investigates how the protein works and what particular amino acids of the protein are important in function. We mutate amino acids in the protein to determine if they important in function. We will also determine associations of membrane protein with each other and analyze protein topology. In addition, we will obtain valuable structural information on the membrane domain of the protein. Our study will give novel information on the structure and mechanism of activity of this physiologically important protein. Ultimately this will lead to a better design of inhibitors and modifiers of the protein that can alter its activity. We will also provide valuable fundamental knowledge on how human membrane proteins function.