G protein-coupled receptors
effectiveness of drug therapy
molecular mechanisms of desensitisation
Areas of expertise
There are more than 800 G protein-coupled receptors (GPCRs) in the genome and they represent a major target for clinically-prescribed drugs. Following prolonged or repeated exposure to agonist drugs that activate these receptors, the GPCRs invariably become less responsive to the agonist, a phenomenon called desensitisation. Desensitisation can limit the effectiveness of drug therapy. This group’s research focuses on the molecular mechanisms of desensitisation of GPCRs.
At the present time we are studying:
• the molecular mechanisms that mediate desensitisation of the ě opioid receptor and its relationship to morphine tolerance
• the co-regulation of group I mGluRs by different protein kinases
• the internalisation, intracellular sorting, and recycling of P2Y receptor subtypes.
We are also beginning to probe the molecular mechanisms that underlie “functional selectivity” at GPCRs, whereby different agonists at the same GPCR can induce different active conformations of the receptor, which can lead to different functional outcomes.