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Alan and Rachel MX beamline

Australian Synchrotron joins Monash and key institutions in $2.9 million new platform to support drug development

Monash University is partnering with the Australian Synchrotron and other key institutions to launch a $2.9 million national project – delivering a robotic laboratory capable of drastically speeding up the invention, trials and commercialisation of medicines by Australian researchers.

The nationally accessible facility, backed by a Medical Research Future Fund (MRFF) National Critical Research Infrastructure grant, will house Australia’s first automated system for high-throughput X-ray crystallography, often referred to as HTX, at the Macromolecular Crystallography (MX) beamlines at the Australian Synchrotron in Clayton.

HTX is a powerful scientific technique that involves blasting tiny biological crystals with X-rays to map the exact 3D shape of disease-causing proteins – revealing how a molecule binds to its target.

MX team Australian Synchrotron
(Left to right) Alan Riboldi-Tunnicliffe, Rachel Williamson, Yogesh Khandokar, Kate Smith and Santosh Panjikar

Synchrotron Principal Scientist (MX) Dr Rachel Williamson and software developer Kate Smith are co-investigators on the grant.

“We are very excited to be part of this important initiative, that extends the analytical capabilities of the beamline to include a High-throughput Crystallographic Fragment Screening platform,” said Dr Williamson.

“Our entire team will be involved in building this capability, using our experience and expertise in crystallography and scientific computation to implement the platform.”

Professor Martin Scanlon, Head of Medicinal Chemistry at the Monash Institute of Pharmaceutical Sciences (MIPS) in the Faculty of Pharmacy and Pharmaceutical Sciences, said the new technology would provide “incalculable ability” to boost capability and capacity while saving time and accelerating productivity.

“When we’re creating a new medicine, we need to design a compound to fit into a specific pocket of a protein, but the protein often changes shape in response. We might plug one hole only to realise the protein has shifted and created two more. Ultimately, the protein decides what fits,” Professor Scanlon said.

“HTX allows us to rapidly capture those changes. It doesn’t instantly solve the puzzle, but it provides the real-time data we need to accelerate that iterative back-and-forth process, allowing us to incrementally build a successful compound.”

Traditionally, finding this perfect fit was a slow and exhausting manual process for researchers. To put the technology into perspective, 25 years ago researchers were flying to Chicago twice a year to collect a fraction of the structural data that will be available. 

“HTX will attract investment and importantly grow the Australian biotechnology and clinical trials economy as more partners invest locally to bring new clinical candidates to market,” Professor Scanlon said.

“Analysis of drug discovery projects successful in generating a clinical candidate showed 65 per cent relied on structural information, most of which were derived from X-ray crystallography.”

Professor Christopher Porter, Director of MIPS, said the HTX platform changes the landscape, shrinking months of painstaking laboratory work down to just a few days, meaning the technology will help researchers quickly turn their medical discoveries into life-changing treatments.

“HTX could allow us to screen a library of ~1,000 compounds automatically in three days without human intervention, which is well beyond what is currently feasible with manual data collection,” Professor Porter said.

It will also introduce a new method called crystallographic fragment screening, which tests tiny pieces of molecules to see which specific parts stick to a disease target best before snapping them together into a final drug.

“Instead of looking for one giant, perfect molecule right away, fragment screening allows us to test small pieces or fragments of molecules to see which individual parts fit into the target best,” Professor Porter said.

“Once we know which fragments stick, our medicinal chemists can pull that information together to build a single highly effective, custom-designed drug.”

The platform will boost sovereign capability in therapeutics, supporting hundreds of researchers across the country investigating treatments for over 40 disease targets, including cancer, HIV, bacterial infections, and neurodegeneration.

Providing the essential structural data fills a critical gap in Australia’s drug development pipeline, giving commercial partners the confidence they need to invest heavily in local biotechnology.

“This platform gives our scientists the world-class engine they need to turn basic biomedical research into the life-saving medicines of tomorrow, ensuring more Australian discoveries are clinically tested and commercialised right here at home,” Professor Scanlon said.

The five-year project represents a very large collaborative effort across the nation's leading scientific institutions, uniting Monash University with ANSTO, the Australian Synchrotron, CSIRO, WEHI, the Australian National University, The University of Western Australia, The University of New South Wales, Griffith University, The University of Adelaide, La Trobe University and The University of Queensland.

The MRFF National Critical Research Infrastructure initiative provides $600 million over 10 years between 2024-25 and 2033-34, increasing Australia’s capacity to conduct health and medical research. Funding is provided through streams including innovation enablers, digitisation of health care, co-investment partnerships and mRNA technology enablers.