Targeted therapies that more precisely identify and attack cancer cells are an area of rapid development globally. Researchers within the VCCC alliance are at the cutting edge of this highly specialised area, thanks to the high-end technology available in the Melbourne biomedical precinct.
The Australian Cancer Research Foundation (ACRF) Translational Proteomic Facility is the first in Australia with the capability for protein-based assays that will complement the use of genomics in targeting cancer therapies.
Profiling the genome of cancers alone does not always provide enough information to make treatment decisions. Mutations in genes cause changes in proteins so researchers need to be able to measure these changes to inform the best targeted therapy option.
The ACRF Translational Proteomic Facility conducts protein-based assays that support the clinical management of patients involved in clinical studies and trials by measuring biological responses to treatment.
Supported by a $2 million grant from ACRF, the facility supports pre-clinical research and clinical trials of targeted cancer therapeutics by providing custom-designed, quantitative analyses of complex mixtures of proteins from human cell lines, xenografts and tissue samples. It has enabled the development of advanced pre-clinical and clinical tissue proteomic and pharmacodynamic biomarker analysis capabilities to help attract clinical trials of novel therapeutic agents to Australia.
The ACRF Translational Proteomic Facility operates as an inter-disciplinary and multi-institutional collaboration between the Departments of Pathology, Pharmacology and Therapeutics, and Biochemistry and Molecular Biology at the University of Melbourne, Proteomics and Metabolomics Victoria at the Bio21 Institute at Melbourne University and the other VCCC alliance partners, particularly the Peter MacCallum Cancer Centre, Melbourne Health, the Walter and Eliza Hall Institute of Medical Research, the Royal Children’s Hospital and the Royal Women’s Hospital. This model located across three separate laboratories, maximises the opportunity for cancer researchers from across the state to access this specialised equipment.
To date, this collaborative facility has enabled access for more than 90 labs across 12 medical research institutes, including the VCCC partners.
This laboratory has upgraded the capabilities in immunohistochemistry in the Parkville precinct to include multiplexed fluorescent immunohistochemistry. It is located within the Centre for Advanced Histology and Microscopy at Peter MacCallum Cancer Centre led by Associate Professor Sarah Ellis and the University of Melbourne Centre for Cancer Research led by Professor Sean Grimmond.
Australia’s first Reverse Phase Protein Array (RPPA) platform enables researchers Australia-wide to perform high through-put quantitation of protein expression, delineating cancer signalling pathways and identifying new target molecules.
This platform is located within the Victorian Centre for Functional Genomics, Peter MacCallum Cancer Centre led by Associate Professor Kaylene Simpson. It is supported by an antibody library with 163 antibodies validated for use in RPPA.
This laboratory has leveraged the Bio21 Institute’s specialised expertise to develop Multiple Reaction Monitoring mass spectrometry (MRM/MS) for multiplexed, quantitative assays of protein isoforms for which good quality antibodies do not exist. Housed in the Mass Spectrometry and Proteomics Facility at the Bio21 Institute, this specialised mass spectrometer is managed by Dr Nicholas Williamson and led by Professor Malcolm McConville and Professor Gavin Reid.
Already, the facility has generated a number of flow-on benefits. These include the employment of specialised staff, support to purchase additional complementary equipment, inclusion in a number of grant applications, and most significantly, $3 million in leveraged funding from Thermo Fisher Scientific. This has enabled the addition of five high-end instruments to the fleet of mass spectrometers housed in the Mass Spectrometry and Proteomics Facility (MSPF) at Bio 21 and led to a Thermo development scientist being embedded within the MSPF to work with Bio 21 researchers to develop new analytic methods, and to provide graduate student scholarship support, placement of demonstration instruments and assistance with technology transfer.
With the facility now established, analytical techniques are being validated, refined and improved so the benefits can flow to many cancer research projects across Victoria.
As Associate Professor Sarah Ellis explains, "The Vectra microscope within the ACRF Translational Proteomic Facility - Multiplexing Tumour Laboratory has enabled multiple cancer research groups at the Peter MacCallum Cancer Centre, the University of Melbourne and other research institutes to investigate the relationship between immune cells, cancer treatment and outcome. Research facilitated by the Vectra microscope has resulted in publications in high quality peer reviewed journals and the demand for this microscope has been used to leverage funding for a world-first automatic immuno-labeling system and powerful image analysis software.”
ACRF’s $2 million grant to support the ACRF Translational Proteomic Facility was officially acknowledged at an event at the Bio 21 Institute and the VCCC building on 19 November, 2018.
Executive Director of the VCCC alliance, Professor Grant McArthur said this highly innovative facility is making a significant contribution to collaborative cancer research in this state. “Targeted therapies are widely regarded as holding the key to improved outcomes for patients, especially those with a poor prognosis. Thanks to the support of ACRF, the work we are doing in this facility is helping us move closer to better, more precise treatments in Victoria,” he said.
Professor Grant McArthur, VCCC Executive Director; Professor Tony Burgess, Chair of the ACRF Translational Proteomics Facility Scientific Committee and Mr Tom Dery, ACRF Chairman.
