DDB's work applies multidisciplinary approaches to define new roles of macromolecules—particularly G protein-coupled receptors (GPCRs) and ion channels—in physiology and disease. This knowledge is utilised to modulate the properties of these macromolecules in a manner that can inform novel drug discovery.
Collectively, GPCRs and ion channels comprise the largest grouping of cell-surface signal-transmitting receptors. Approximately 40% of current pharmaceuticals target less than 10% of these proteins, leaving many untapped opportunities to discover new biology and therapeutics that regulate these receptors.
Furthermore, GPCRs and ion channels are key regulators of many significant health burdens, including neuropsychiatric disease, metabolic disease, pain and inflammation, cardiovascular disease and numerous cancers.
DDB is leading the world in the study of novel modes of regulating drug receptors, in particular:
- Allosteric modulation—the interaction of drugs and other substances at receptor sites, topographically distinct from the endogenous hormone/transmitter binding site.
- Ligand-biased signalling—the ability of molecules to promote distinct receptor conformations that yield strikingly different functional outcomes.
The two major tiers to these studies are to understand how they impact the functioning of receptor proteins, and how they can be exploited to direct novel drug discovery.
- whole-animal imaging core
- radioisotopic assay core
- molecular modelling
- mammalian cell culture
- murine disease model facility (MDMF)
- fluorescence-associated cell sorting (FACS)
- protein expression and purification
- cell signalling core
- molecular biology core
- yeast cell biology
- ex vivo pharmacology