Professor Patrick Sexton and Professor Arthur Christopoulos

Monash University

Australian researchers exploring “dimmer switch” medicines that could help patients with obesity, diabetes and schizophrenia, have won the prestigious GSK Award for Research Excellence.

The ground-breaking research by Professors Arthur Christopoulos and Patrick Sexton from Monash University offers hope for people with chronic conditions. According to the researchers, medicines that can be “turned up” or “turned down” rather than “on and off“ will give doctors more variability to tailor treatment to a patient’s medical needs. Medicines based on this principle will allow patients to lead a more normal life without the side effects associated with existing drugs.

Their research into G protein-coupled receptors (GPCRs) has begun to unravel the complexities of drug action that could lead to more targeted medicines. The “dimmer switch” of a protein, known as the allosteric site, allows the targeted protein to be dialled up or down in a way that was not previously possible.

Both professors were congratulated on winning the GSK Award for Research Excellence at the annual Research Australia Awards in Sydney. The award is well recognised among the Australian medical research community and includes an $80,000 prize that will help the winners progress their work.

“Many medicines have unwanted side effects because they work by simply turning receptors on or off, even though we know that most of these proteins have the potential for more graded levels of response that can become highly relevant in the contexts of tissue specificity, disease and individual patient profiles. We have discovered a more tailored way to exploit this functionality, by targeting regions on the receptors that act more like dimmer switches rather than on/off switches,” said Professor Sexton.

Both professors are world leaders in the study of G protein-coupled receptors (GPCRs), the largest class of drug targets, and the application of analytical pharmacology to understand allosteric modulation. In recent years their work has challenged traditional views of how medicines were thought to work.