Waterhouse and Wang's big win

By Staff Writers
Thursday, 20 September, 2007

Peter Waterhouse and Ming-Bo Wang have won the 2007 Prime Minister's Prize for Science, worth $300,000.

The CSIRO duo won the award for their ground-breaking discovery of 'hairpin' or double-stranded RNA-induced gene silencing in plants. The naturally occurring mechanism has wide application in human, animal and plant research.

US scientists Craig Mello and Andrew Fire won the 2006 Nobel Prize for a similar discovery in animals.

In the 1990s Waterhouse, Wang and colleagues in CSIRO Plant Industry began investigating the immune system of plants with the aim of developing better ways to protect crop plants from viruses.

The plant immune system process was first described in the 1920s but its mechanism has been a mystery. Plant viruses are mostly RNA-based. When they infect cells, the viruses hijack the cellular machinery and make double-stranded RNA as a step to creating new RNA viruses.

Normally, there is no double-stranded RNA in uninfected plant cells. In 1995, working with potato and tobacco plants, the research team discovered that plants might be using this double-stranded RNA to mount a defence against viral infection.

That led to a series of experiments to understand the mechanism and also to see if it could be harnessed to modify plants, making them less susceptible to disease for example.

In 1997, working with rice and tobacco plants, Waterhouse and Wang found that plants have mechanisms to identify and cut up the double-stranded RNA produced by invading viruses. The plants then bind these bits of alien RNA to a nuclease which is able to locate and destroy the normal single-stranded RNA of the virus.

In the meantime, the pair realised that if double-stranded RNA could be used by the plant cell to stop virus genes, then it could also be used to stop the expression of normal plant genes.

If you can destroy the message that that the gene sends to the protein factories of the cell in the form of single-stranded messenger RNA, the protein doesn't get produced and the gene is effectively silenced.

"We thought 'this is great!'" Waterhouse said. "Now we know how we can kill off any RNA that we like in a cell. All that we have to do is to trick the cell into believing that the messenger RNA of the gene that we want to silence, is a virus."

So they created a special gene code to do the job: the gene code, or sequence, for an RNA molecule that loops back on itself to create a hairpin-shaped double-stranded-like RNA molecule that the plant cell recognises as foreign.

If you want to turn off a gene that makes flowers blue, for example, you can insert the special gene sequence into the plant DNA. It will include part of the 'blue flower' gene plus the special sequence to create hairpin RNA.

The plant makes RNA from the introduced gene. The special RNA sequence forms the hairpin double-stranded-like RNA molecule. The plant cell recognises the double-stranded RNA as foreign, breaks it up and uses the broken up pieces as a guide to attack any RNA in the cell with the same gene sequence.

The message is destroyed and the 'blue flower' protein never gets made. At the same time, Mello and Fire demonstrated a similar process for gene silencing in animals.

Today, the technology is licensed to thousands of researchers around the world and has generated more than 100 patents to date.

"CSIRO's Food Futures Flagship is using our technology to develop oilseeds with a high omega-3 content and wheat with high levels of resistant starch, both of which are important for human health," Wang said.

"Overseas examples include a national program to develop rice that is resistant to rice stripe virus in China, improving the yield and nutritional value of cassava in Africa and a US project using the technology to make antibodies in plants for the treatment of human diseases including non-Hodgkin's lymphoma and inflammatory conditions such as arthritis."

Meanwhile, marine scientist Dr Beth Fulton has won the Life Scientist of the Year award, worth $50,000.

Fulton works with CSIRO Marine and Atmospheric Research in Hobart as part of the Wealth from Oceans National Research Flagship.

The award recognises her achievements in marine ecosystem modelling and her impact on understanding climate change and managing the effects of fishing.

Her research involves identifying new directions in marine ecosystem modelling and model development. She was the first person to systematically explore the optimum level of complexity for ecosystem models.

Atlantis, which she developed for whole of ecosystem modelling for marine environments, is the only model in the world that gives equal attention to the biophysical and human components of marine ecosystems.

Atlantis was rated the world's best for strategic evaluation of marine management issues by the Food and Agriculture Organisation in 2007 and was the first model to be used to assess a whole of fishery management plan from an ecosystem perspective.

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