New drug discovery facility for Melbourne

By Ruth Beran
Thursday, 22 September, 2005

The privately funded Australian Cancer Research Foundation (ACRF) has awarded a grant of AUD$900,000 to Melbourne's St Vincent's Institute (SVI) to establish a rational drug discovery facility for cancer research.

The facility, located at St Vincent's Health Fitzroy campus, will be overseen by associate directors Prof Michael Parker and Assoc Prof Matthew Gillepsie.

"The Australian Cancer Research Foundation grant is to enhance the facility we have at the Institute, in three areas," said Parker. "It will speed up the whole process from discovery to testing compounds in animals."

Firstly, the grant will enable SVI to upgrade its existing x-ray facilities and has allowed the purchase and installation of a new x-ray generator and detector for x-ray crystallography.

"Not only is it state of the art but at the moment it's considered to be the strongest source of x-rays per unit area, anywhere in the world, in-house," said Parker.

X-ray crystallography allows researchers to determine the atomic structures of proteins. Suitable crystals of proteins are exposed to x-rays and the scattering information is used to determine the protein's 3D atomic structure.

"At the moment we have access to synchrotrons overseas which are used for x-rays, but there's a long waiting list to get on those," said Parker. "One of the great things with the new x-ray system is because it is so powerful, we can work with small crystals in-house."

Parker said that solving the structure of a protein can take weeks or months and possibly up to a year. "It is a puzzle and we use various tricks to solve that puzzle," he said.

The grant will also be used to upgrade SVI's virtual screening facility, where databases containing the structures of more than four million compounds are used to dock compounds, one at a time, into active sites on the protein, with the aim of finding drug-like molecules.

"The money's going to be used to buy more powerful computers, and also is going to be used to buy some commercial licenses for some of the software we use, so we can actually straddle the academic industry bridge," said Parker.

Thirdly, the ACRF grant will be used to improve SVI's medium-throughput screening facility where the compounds are put through cell-based screens to ensure they are active in cancer cells. "We can [now] buy various instruments that will enable us to look at some of these compounds from the virtual screening in a reasonably high throughput manner," said Parker.

Internally, SVI has various cancer projects underway with Gillespie, the other chief investigator on the proposal, working specifically on bone cancer, said Parker. SVI also has collaborations with the University of Queensland on a human growth hormone receptor, the Austin Hospital on a target in prostate cancer, the Peter MacCallum Institute on a protein implicated in cancers, the Hanson Centre, Adelaide on a cytokine receptor and with Italian scientists on proteins that attack anti-cancer drugs.

The SVI is also part of a consortium which recently received STI funding from the Victorian government for the Bio21 Nanolitre Protein Crystallisation Facility. In collaboration with the CSIRO, Austin Research Institute, Walter and Eliza Hall Institute, and the Victorian College of Pharmacy, a total of $1.75 million will be used to purchase such things as crystallisation robots, to improve protein crystallisation and the production of protein crystals.

"We're in the process of buying these robots," said Parker. "That's going to speed up the crystallisation side of things dramatically."

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