Grant: Operating Grant

Cystic fibrosis (CF) is the most frequent orphan disease in Canada, and the CFTR gene was discovered by Canadian and US researchers 22 years ago. The CFTR gene codes for a cell surface protein that transports chloride and the most frequent mutant protein is able to transport chloride, but is retained inside the cell. We have identified small molecules that are good correctors of this trafficking defect of the CFTR mutant protein trafficking and these are under intensive development. We have observed that correctors that work well in transformed human lung-derived epithelial cell lines do not necessarily work well in cells obtained from CF patient lung transplants. In addition we have noticed a considerable variation in the functional response to correctors in CF patient lung cells obtained from different individuals. This proposal will address the questions, why do correctors function differently in different cells, and do outside stimuli affect the corrector's ability to function? Our overall hypothesis is that this knowledge will guide us to better targets for drug development for cystic fibrosis.