Molecular Physiology Laboratory
G protein-coupled receptors are the largest family of membrane proteins in the human genome. They mediate a great diversity of physiological functions and are particularly amenable to modulation by small molecule drugs, making them important targets for therapeutic interventions. All G protein-coupled receptors communicate an extracellular signal across a biological membrane, via a change in the conformation of the receptor protein. Our research aims to understand how binding of ligands to the extracellular surface of GPCRs induces distinct cellular responses.
The Molecular Physiology Laboratory focuses on two G protein-coupled receptors, the gonadotropin-releasing hormone (GnRH) receptor, which regulates reproduction, and the CCR5 chemokine receptor, which mediates HIV infection. We use site-directed mutagenesis of the GnRH and CCR5 receptors, combined with a range of in vitro functional assays to study how receptor proteins change conformation in response to binding of different ligands (hormones, chemokines, drugs or HIV proteins) and how the changes result in different cellular responses.
Better understanding of how G protein-coupled receptors function has applications in development of new drugs for treatment and prevention of reproductive disorders and HIV infection.
Dr Colleen Flanagan
Dr Michael Madziva