Research Project
3245449
Cystic fibrosis (CF) is a common inherited disease which affects the epithelia of the lungs, sweat glands, salivary glands, gut, pancreas and male reproductive tract, and which is characterized by abnormalities in electrolyte and fluid transport. Although there is substantial evidence that the primary defect in CF cells is expressed as a reduced apical membrane chloride permeability, it is only in respiratory tract epithelia that the defect has been linked to a particular type of chloride channel. The specific aims of this project are: (i) to characterize, using whole-cell current recordings, the macroscopic anion currents, and their regulation in human pancreatic and epididymal duct cells, and to identify which conductance(s) is/are affected by CF; (ii) to investigate the effects of antibodies, prepared against specific cytoplasmic domains of CFTR (the CF gene product), on these anion currents; and (iii) to monitor the properties of anion conductances in genetically manipulated pancreatic and epididymal duct cell lines in which the expression of CFTR has been modulated. My long term objectives are to identify the anion conductance(s) in glandular epithelial cells that are affected by CF, and to gain an insight into the role of CFTR in regulating this (these) anion conductance pathways.
