This discovery builds on years of cystic fibrosis (CF) research at The Hospital for Sick Children (HSC), including the discovery of the CF gene in 1989. After the discovery of the gene, research focused on determining the function of the protein that the gene encodes. Each gene in the human genome codes for a unique protein. The gene is the molecule of information, but the protein that is then biosynthesized in the cell actually carries out the bodily function. In the case of the CF gene, the protein (named CFTR) regulates the necessary balance of sodium chloride (salt) across the cell membranes in the lungs and pancreas.
"We now have a clearer picture of why the protein doesn't function properly in the milder form of cystic fibrosis - segments of the protein are sticking together, interfering with the flow of chloride in and out of the cell," said Dr. Charles Deber, the study's principal investigator, a senior scientist in the HSC Research Institute and a professor of Biochemistry at the University of Toronto.
Cystic fibrosis is not just one distinct phenotype, as researchers have found hundreds of different mutations in the CF gene and the corresponding protein. The milder form of cystic fibrosis, also known as pancreatic sufficient CF, occurs in 10-15 per cent of CF patients. In this form of the disease, which often manifests as lung disease and male infertility, CFTR is able to carry out partial function. In the more severe forms of cystic fibrosis, the protein never assembles properly and no chloride can be transported.
"This opens the door for new avenues of research in terms of rational drug design," added Dr. Deber. "We will look for molecules that could possibly break up the abnormal bond that is
Contact: Jennifer ten Westeneind
The Hospital for Sick Children