Grant: Operating Grant

The cystic fibrosis gene dictates the synthesis of a protein (called CFTR) which is normally resides in the limiting membrane of cells and responsible for the normal water content or hydration of the lung. Genetic mutations in the cystic fibrosis gene can impair the protein's ability to accumulate at cell surface and/or remain there long enough to execute its function. The mechanism of delivery of the normal CFTR to and the premature removal of mutants from plasma membrane is not known and constitutes the major focuse of the present proposal. We propose to identify the molecular basis of CFTR normal delivery to its appropriate cellular location, as well as the cellular mechanisms that discriminate between the normal and mutant CFTR structure. We will investigate the cellular and biochemical mechanisms of mutant CFTR recognition and premature elimination, one of the most common causes of cystic fibrosis at the cellular level. The results may identify novel drug targets in cystic fibrosis that could help to alleviate the clinical symptoms in this devastating disease.