Fields of Study
Areas of Interest
Research in the laboratory is focused on two main areas: ABC transporters and phage proteins. We use a combination of NMR spectroscopy and other biophysical tools to obtain information about the structure, interactions, and dynamics of proteins.
ABC transporters are multi-domain, integral membrane proteins found in all species and consist of two repeats each comprised of a membrane spanning domain (MSD) and a cytoplasmic nucleotide binding domain (NBD). ATP binding and hydrolysis at the NBDs results in transport of solutes across biological membranes. ABC proteins are of vast biomedical importance. ABC protein-mediated pumping of cytotoxic molecules from cells confers multidrug resistance to bacterial and tumour cells. Furthermore, many genetic diseases are caused by mutations of specific ABC proteins. We are studying two different ABC proteins in the lab: (1) Ycf1p, a Cd transporter in yeast; (2) sulfonylurea receptors (SUR), which form regulatory subunits in K+ channels. Studies of Ycf1p are aimed at understanding the basic mechanisms of regulation of ABC transporters. Studies of SUR proteins are aimed at understanding the molecular defects caused by disease-causing mutations in the proteins and how we can correct these defects with drugs.
Our work on phage proteins is focused on an HNH endonuclease a the lambda-like bacteriophage. The HNH protein is critical for the phage replication cycle. We are performing structural studies of the protein to understand the molecular basis for its function in phage morphogenesis. This work will ultimately lead to generation of designer phages that can be used to treat antibiotic resistant bacteria.