Thursday, 17 September 2009 3:40pm
Otago scientists have gained $730,160 to support two international health research collaborations involving new approaches towards drug discovery in HIV-1, genetic diseases and melanoma.
The Health Research Council of New Zealand is supporting the projects through its International Investment Opportunities Fund (IIOF). The fund focuses on enabling outstanding New Zealand researchers to build research collaborations with overseas research teams.
The projects are:
Drug discovery targeting a novel step in HIV-1 biology, and overriding gene mutations
24 months, $396,538
Professor Warren Tate, Department of Biochemistry, University of Otago
Lead international partner
Dr John Phillip Parisot, The Walter and Eliza Hall Institute of Medical Research, La Trobe R&D Park, Victoria, Australia.
We have developed a new patented cell-based test to explore a novel drug target in HIV-1. HIV-1 uses a unique genetic mechanism to regulate synthesis of its structural and enzyme proteins in the correct amounts crucial for infectivity. Current methods for studying this mechanism are slow and use enzyme markers requiring expensive chemicals for detection. Our test uses reporter proteins that fluoresce when energised by light, is 90 per cent cheaper and ten-fold quicker. Preliminary drug screens showed that our system is sensitive for detecting changes at the HIV-1 target site.
Importantly, it can also accurately quantify gene mutation sites in human genetic diseases. We want to test our system further at the Walter and Eliza Hall Institute’s High Throughput Chemical Screening Facility in a new collaboration to assess its impact for identifying not only new drug compounds against HIV-1, but also drugs that can alleviate the consequence of genetic mutations.
Targeting melanoma initiation and progression: developing ABCB5 inhibitors
12 months, $333,622
Professor Richard Cannon, Department of Oral Sciences, University of Otago
Lead international partner
Professor Larry Sklar, Professor of Pathology; Director of the University of New Mexico Center for Molecular Discovery
Melanoma is the most dangerous form of skin cancer: it is invasive and in 2004 caused 249 deaths in New Zealand. Early stage melanoma can be treated by surgery but in advanced stages it is lethal. Chemotherapy is not usually employed as melanomas are highly resistant to many anti-cancer drugs, and the melanoma progenitor cells express the drug efflux pump ABCB5. We have experience in expressing efflux pumps, including another anti-cancer drug efflux protein, Pglycoprotein, in the model yeast Saccharomyces cerevisiae.
We propose to clone and express human ABCB5 in S. cerevisiae and develop a fluorescent substrate efflux assay. Our collaborator, Professor Sklar of the University of New Mexico Cancer Center, will use this assay in his unique, high throughput screen, to search for ABCB5 inhibitors in a library of drug-like compounds. Further collaboration will lead to the development of novel therapeutic approaches for preventing melanoma invasion and metastasis.
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