A major new initiative: Drugs Discovery Biology joins MIPS

Drug Discovery Biology (DDB), the newest theme in the Monash Institute of Pharmaceutical Sciences (MIPS), will be established at the Parkville campus in July.

Professors Patrick Sexton, Arthur Christopoulos and Roger Summers, from the DDB theme, use a multidisciplinary approach to study the regulation of receptors to find novel molecules that can eventually become drugs.

Research currently focuses on understanding novel modes of regulation of G protein-coupled receptors (GPCRs) in an effort to identify novel targets or approaches for drug discovery. The function and health of living cells depend on how they respond to the many physical and chemical stimuli that continually bombard them. Most chemical cellular stimuli comprise hormones, peptides and neurotransmitters that impart their actions by binding to specific cell surface receptor proteins. GPCRs represent the largest superfamily of all receptors (around 2% of the human genome) and are the targets for nearly 30% of all currently used therapeutic drugs.

The work of the DDB theme encompasses investigation across virtually all levels of GPCR structure/function, including analysis of the functional significance of single nucleotide polymorphisms; alternate mRNA splicing; signalling via G proteins and downstream messenger systems; interaction of receptors with regulatory accessory proteins; novel allosteric GPCR binding sites; and mathematical and molecular modelling of GPCR-ligand interactions

Currently within the Faculty of Medicine, Nursing and Health Sciences, the DDB’s move to Parkville and integration within MIPS means increased synergy between Monash faculties and among the existing MIPS research themes. The DDB team’s work focuses on the early phase of drug development, including target identification, target validation, hit discovery, mechanism of action, proof of concept and in some cases early preclinical animal models. Increased linkages with the Medicinal Chemistry and Drug Action theme and the other MIPS themes means that the DDB team has a greater coverage of target and chemical space and an increased capacity to move promising candidates up the drug discovery pipeline.

Molecular model of a G protein-coupled receptor indicating potential binding pockets for novel classes of drugs.

“The move to MIPS and to Parkville is a real benefit to us. It increases the translational potential of what we do,” said Professor Sexton.

“Being co-located with the three existing MIPS themes, we will have greater synergy and more translational opportunities to undertake higher impact, multi-disciplinary projects.”

Professor Christopoulos said that the new infrastructure provided by the theme is applicable to other drug targets, outside the DDB area of specialty.

“This framework is transferable to other types of targets,” he said. “It will also give us the opportunity to co-develop new types of infrastructure and to broaden our ability to engage with industry groups.”

MIPS, which comprises the largest and most experienced group of pharmaceutical scientists in Australia, takes a lead role in drug discovery and development, pharmaceutical research and training.

“The establishment of MIPS is a great innovation,” said Professor Summers. “Nowhere else in Australia can you go from the target to the molecule to an optimised preclinical drug candidate that may be ready for early phase clinical trials.”

The new facilities, which comprise the entire third floor of the new fourth building at the Parkville campus, were designed specifically to suit DDB requirements. A purpose-built open-plan laboratory is supported by discrete spaces dedicated to specialist services such as receptor binding, cell culture, bacterial and yeast work, cell-based signalling assays, molecular modelling and protein chemistry.

The facilities will house the 35 team members and can accommodate 54 staff, allowing for eventual expansion of the DDB team or for staff from other MIPS themes to work cooperatively.

“The integration of DDB into MIPS further improves cooperation between the faculties of Medicine, Nursing and Health Sciences, and Pharmacy and Pharmaceutical Sciences,” said Professor Bill Charman.

“In most universities there would be myriad organisational and political reasons why such a unique and strategic collaboration would not happen. However, this is not the case at Monash, where the focus is on assembling leading teams to undertake high impact research in collaborative multi-disciplinary environments. MIPS is now uniquely placed in the GPCR field to undertake drug discovery and development – and is another terrific and tangible example of ‘better medicines by design’, the MIPS
tag line.”