The cystic fibrosis transmembrane conductance regulator (CFTR) is a novel member of the ATP-binding cassette (ABC) transporter superfamily that forms an anion channel with complex regulation. CFTR is predominantly located in epithelia lining ducts and tubes throughout the body, although it is also expressed in some non-epithelial tissues, most notably cardiac myocytes. In epithelia, CFTR provides a pathway for the movement of chloride (Cl-) and bicarbonate anions across the apical (lumen-facing) membrane and a key point at which to regulate the rate of transepithelial salt and water transport.

Dysfunction of the CFTR Cl- channel is associated with a wide spectrum of disease. Mutations that, in general, abolish the function of CFTR cause the genetic disease cystic fibrosis (CF), which affects multiple organ systems in the body. By contrast, some forms of male infertility, chronic pancreatitis and bronchiectasis are caused by mutations that probably preserve partial CFTR function. These conditions, termed CFTR-related diseases, affect a single organ system in the body. Increased or inappropriate activity of the CFTR Cl- channel is associated with other diseases, such as secretory diarrhoea and autosomal dominant polycystic kidney disease.

In our studies of the CFTR, we have three specific research goals:

• To understand the relationship between the structure and function of the CFTR Cl- channel

• To learn how CF-associated mutations cause a loss of CFTR function

• To identify new modulators of CFTR that might prove to be of value in the treatment of disease and elucidate their mechanism of action.