Molecular Endocrinology - GPCRs

This group studies the molecular function of G-protein coupled receptors (GPCRs) and their signalling pathways. GPCRs are a family of about 1000 different cell surface sensors in the human body. Their function is diverse and, among many more, includes the detection of light (vision), odorants (smell), the regulation of growth, reproduction, immune responses etc. Not surprisingly, almost half of all currently available prescription drugs modulate GPCR function to mitigate various diseases. The market for GPCR based drugs is large with annual sales of US$23.5 billion for drugs targeting GPCRs directly.

The group's main goal has been to determine the molecular basis of drug recognition and signalling by pituitary GPCRs controlling reproductive and thyroid function. Gonadotropin-releasing hormone (GnRH) is the master hormone in the control of reproduction and the receptors for GnRH have been the central focus of these studies. Ligands for these receptors have huge clinical application - particularly GnRH analogues, which generate revenues in excess of US$1 billion annually for treatment of prostate and breast cancer and gynaecological disorders. Other receptors under investigation include thyrotropin-releasing hormone (TRH), receptors which are involved in controlling the thyroid axis, nutritional states and obesity as well as Orexin receptors, which are also involved in obesity.

Another research focus of the group is receptor dimerisation and its role in GPCR function, signalling and pharmacology. This concept is believed to play an important role in the future for the design of highly specific and effective drugs. Novel technologies for the analysis of GPCR dimer function and drug discovery are currently under development.

The group has expertise in, and access to, a wide repertoire of modern methodologies to study GPCR function, including genetic engineering, recombinant protein expression, tissue culture, ligand binding, intracellular signalling etc. This laboratory was also one of the 'pioneers' around the world to apply bioluminescence resonance energy transfer (BRET), an advanced protein-protein interaction assay technology. This method has a multitude of applications and the availability of this technology in Perth has resulted in new collaborations with other local, national and international research groups.

Senior Research Staff

Dr Kevin Pfleger Head, Molecular Endocrinology - GPCRs Research: G-protein coupled receptors; bioluminescence resonance energy transfer

A/Professor Karin Eidne Head, Molecular Endocrinology - GPCRs Research: novel G-protein coupled receptor interactions