Profile: Senior Scientist, SickKids Research Institute
Department: Biochemistry, University of Toronto
Lab: Bear Lab
At present, our specific studies focus on understanding the molecular and structural basis for Cystic Fibrosis, the disease caused by mutations in the gene, CFTR. Our group developed the means for purification and functional reconstitution of the protein product of CFTR (Bear, C. et al. Cell 1992). Further, we showed in electrophysiological studies in planar lipid bilayers, that wild type CFTR functions as a chloride channel and as an ATPase and certain disease causing mutations in CFTR cause specific defects in these functions (Li, C. et al. Nature Genetics 1993) (Li, C. et al. J. Biol. Chem. 1996) (Pasyk, E. et al. J. Biol. Chem. 1998), (Kogan, I. et al. J. Biol. Chem. 2001). Recently, we have developed novel methods for assessment of the quaternary structure of CFTR in cell membranes obtained from native tissues and the separation and reconstitution of each structure (Ramjeesingh, M. et al., Biochem. J. 1999) (Ramjeesingh, M. et. al. Biochemistry, 2000) . We found that while monomeric CFTR is the minimal functional unit, the protein self-associates to form dimers at the plasma membrane. We are currently using our reconstitution system to determine the functional consequences of this self association and the impact of disease-causing mutations on this process.