Peter Waterhouse and Ming-Bo Wang
The human genome project found we have around 32,000 genes—only a few more than other animals, insects and most plants. Knowing how those genes are turned on and off is a key to understanding how a few thousand genes interact to create a human, a fly or a wheat plant.
While investigating how plants respond to virus attack, Peter Waterhouse, Ming-Bo Wang and their team at CSIRO Plant Industry in Canberra discovered a new way to control plant genes—by using the plant’s own viral defence mechanisms.
They realised they could harness the plant’s immune response to stop information being transferred from any gene in the cell nucleus to the protein factories of the cell. The genes weren’t destroyed but they were effectively gagged or silenced.
Around the same time, US scientists discovered a similar form of gene silencing in animals—and received a Nobel prize for their work.
But it’s Peter and Ming-Bo’s discovery that is finding wider application across the biological sciences. It’s generated more than 100 patents to date and is helping us understand the workings of plant, animal and human genomes.
For their discovery of how to silence genes in plants, Peter Waterhouse and Ming-Bo Wang receive the 2007 Prime Minister’s Prize for Science.
In the 1990s Peter Waterhouse, Ming-Bo Wang and their colleagues in CSIRO Plant Industry were investigating the ‘immune system’ of plants with the aim of developing better ways to protect crop plants from viruses. It’s very important work. One virus alone—barley yellow dwarf virus—cuts the global wheat harvest by about two percent, and a range of further viral diseases lead to reduced yields in other crops around the world.
The concept of an immune defence in humans has been well understood for many years. It’s less well known that plants can be protected from virus attack by ‘immunisation’—exposure to a mild strain of the virus. The 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 they hit the jackpot.
Working with rice and tobacco plants, Peter and Ming-Bo 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 an enzyme (a nuclease) which is able to locate and destroy the normal single-stranded RNA of the virus.
In the meantime, they 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—a very useful way of dealing with genes that are not particularly welcome from our perspective, such as the ripening gene in fruits which causes them to bruise and rot early.
And it could be used in other ways, for example to silence a gene for a particular colour in flowers.
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!’ 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,” says Peter.
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, a US team demonstrated a similar process for gene silencing in animals. They went on to win a Nobel prize.
But as the years passed, researchers around the world have come to realise that Peter and Ming-Bo’s technique was more powerful and could be used in plant, animal and human cells.
Today, the technology is licensed to thousands of researchers around the world and has generated more than 100 patents to date.
“The science has been exciting,” says Ming-Bo. “Exploring the world of intellectual property has been a more challenging but necessary experience.”
“At one point we seemed to spend more time talking law then we did talking science,” says Peter. “But it’s led to a strong patent position that gives people the chance to use the technology and also brings returns to CSIRO and Australia.”
While the rest of the world finds new ways to apply the technology, Peter and Ming-Bo are applying their work to projects that have the capacity to transform agriculture and reduce greenhouse gas emissions.
“We can use the technology to insert genes into plants that will protect them against multiple viruses,” says Ming-Bo.
“I’d like to see gene-silencing used to combat climate change,” says Peter. “For example, we are working to create plants that could produce biofuels customised for different engines. These crops would be much more efficient at making biofuels than the current processes using corn or sugar,” he says.
“They’d capture the CO2 when they grow, and release it when used as fuel—a closed circle with no net carbon emissions.”
Peter Waterhouse
Academic record
1981 PhD, Scottish Crop Research Institute, University of Dundee
1977 BSc, University of Newcastle upon Tyne, UK
Employment record
2006- Chief research scientist, CSIRO Division of Plant Industry
2000-2006 Senior principal research scientist, CSIRO Division of Plant Industry
1999- Leader of Genomics subprogram, CSIRO Division of Plant Industry
1995-98 Program leader of Plant Defence for the Cooperative Research Centre for Plant Sciences
1993-99 Leader of Virology subprogram, CSIRO Division of Plant Industry
1993-2000 Principal research scientist, CSIRO Division of Plant Industry
1992-93 Sabbatical leave at the Centre for Protein Engineering, Medical Research Council Centre / University of Cambridge / Cambridge Antibody Technology Company, Cambridge, England
1991-98 Cooperative Research Centre for Plant Sciences Project leader
1991-92 Acting program leader in Plant Defence, CSIRO Division of Plant Industry
1989-91 Leader of Virology subprogram, CSIRO Division of Plant Industry
1986-93 Senior research scientist, CSIRO Division of Plant Industry
1981-86 Research scientist, CSIRO Division of Plant Industry
1977-78 University of Cambridge, England
Recent awards
2007 Winner of The Bulletin’s Smartest Scientists in Australia
2005 CSIRO Chairman’s Medal
2003 IMTC-ISI/Thomson ‘Most Highly Cited in Field’ Award
2002 Victor Chang Medal
Ming-Bo Wang
Qualifications
1990-94 PhD, University of Durham, Durham, UK
1984-87 MSc, Chinese Academy of Sciences, Beijing, China
1980-84 BSc, Peking University, Beijing, China
Relevant research experience
1998-now Senior research scientist, CSIRO Division of Plant Industry
1994-1998 Postdoctoral Research Fellow, Research Fellow Cooperative Research Centre for Plant Science
1990-1994 PhD Department of Biological Sciences, University of Durham, UK
1987-1990 Junior Research Scientist, Biotechnology Research Centre, Chinese Academy of Agricultural Sciences, Beijing, China
Scholarship and awards
2007 Winner of The Bulletin’s Smartest Scientists in Australia
2005 CSIRO Chairman’s Medal
1999 CSIRO Plant Industry Chief’s Award
1990-94 Rockefeller Foundation Fellowship