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Glutathionarsenoxide (GSAO) is an organoarsenical – a synthetic peptide that includes an atom of arsenic. Professor Philip Hogg and colleagues at The University of New South Wales Cancer Research Centre created the compound to explore the workings of a particular protein, but then noticed something unusual: their compound was also extremely good at knocking out the mitochondria in cells.

But not just any cells: "We really just followed our nose and realised, in vivo, GSAO was very selective for the cells that make new blood vessels," says Professor Hogg, biochemist and co-director of the Lowy Cancer Research Centre. The discovery has since earned Professor Hogg and colleagues numerous medical and research prizes as it has enormous implications for tumour treatment.

Angiogenesis, the ability to make blood vessels, is essential for a tumour to be able to grow and spread, so it has become a major target for anti-cancer drug research. Most anti-angiogenesis drugs to date have targeted specific proteins involved in the process, such as tyrosine kinases.

However GSAO is unique in targeting and inactivating the mitochondria, which are a cell's energy powerhouse. Without mitochondrial activity, endothelial cells die, and without endothelial cells, a tumour cannot make new blood vessels to supply it with oxygen and nutrients and so cannot grow or spread.

"In principle the treatment should be effective against all solid tumours, such as breast, prostate, colon and brain," Professor Hogg says. Because the treatment stops the tumour growing but does not reduce or remove it altogether, Professor Hogg envisages GSAO-based therapy would be used in conjunction with conventional chemotherapy or other anti-angiogenesis agents. "We're trying to attack the cancer from several different points, targeting different aspects of the tumour growth process," he says.

Studies in animals have shown that GSAO causes the tumour to go into stasis, and a UK-based clinical trial in a small group of patients with end-stage cancer is underway, with preliminary results expected by the end of the year.

Compound may identify dying tumours

Cancer therapy can be a hit-and-miss affair. Although newer and more targeted therapies are constantly being developed and older therapies refined, the likelihood remains that some patients will fail to respond to treatment or experience a disease relapse.

One of many challenges in treating cancer is identifying these patients as early as possible in the treatment course, and altering their treatment to be more aggressive or take a different treatment approach entirely. However it is difficult to spot changes in a tumour before it begins to reduce in size.

In another elegant example of research serendipity, Professor Hogg and colleagues' work on anti-mitochondrial cancer drugs has yielded a compound that could be used early in treatment to assess whether a tumour is responding to treatment.

The compound, a derivative of GSAO, can be used to detect dying or dead tumour cells. "When a cell starts to die, it takes this compound up in a big way compared to viable cells," says Professor Hogg. "Normally cells do take this up but they pump it out just as quickly."

When a cell starts to die, the process for removing the compound shuts down, so it accumulates in the cell. By labelling the compound with a radioisotope, scientists can detect whether the compound is accumulating in tumour cells, and therefore determine whether treatment is destroying the cells.

Unlike conventional methods of monitoring the progress of treatment, which are often done after several cycles of treatment, Professor Hogg's method could, in theory, be used to detect changes in the tumour as little as one day after treatment starts.

The discovery has attracted international attention, and the compound has now been licensed to a US pharmaceutical company that will take it into the clinic.

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Sexual 'calling cards' could one day be used to ensnare one of Australia's most notorious pests – the freshwater carp (Cyprinus carpio).

Australian researchers are closely monitoring the efforts of US researchers to isolate and purify the pheromones left by sexually mature male carps to attract females. The pheromones could provide an efficient method of trapping, and removing, the fish from waterways.

Using pheromones, however, is just one of many tools being investigated or implemented as part of an Invasive Animals CRC project that seeks to rid the Lachlan catchment, part of the Murray Darling Basin, of carp — regarded as an ecosystem vandal.

Called the River Revival Lachlan River Carp Cleanup project, the project involves local communities, fisheries researchers and government bodies. The Lachlan catchment is uniquely positioned for testing various carp control methods because it is largely isolated from the rest of the Murray-Darling Basin and only connects with the Murrumbidgee River in exceptionally high flow – such as a one in 20 year flood.

Within the catchment there are three known and two other potential carp 'hot spots' — the Great Cumbung Swamp (near Oxley), Lake Brewster (Hillston), Lake Cargelligo, Lake Cowal (West Wyalong) and Lake Wyangala (Cowra). All are part of efforts to control carp populations at their source. The project has brought together a large body of expertise — the CRC, the Lachlan Catchment Management Authority (LCMA), NSW Department of Primary Industries (NSW DPI), South Australian Research and Development Institute (SARDI), Victorian Department of Sustainability and the Environment (VDSE), Kingfisher Research, K&C Fisheries, State Water, the Lachlan Aboriginal Natural Resource Management Group and the community, including shire councils, recreational fishing clubs, Landcare and Fishcare.

In the project's first two years, now being completed, there were several goals:

• to benchmark the status of the carp population;
• determine recruitment levels in hotspots; and
• explore riverbank stability, water quality, aquatic vegetation cover, macro-invertebrate and native fish community composition, and social attitudes towards carp.

A team led by NSW DPI's Dean Gilligan has recorded ecological data and found that carp dominate the fish population throughout the catchment, making up 76 per cent of the fish biomass in the Lachlan River alone.

Interestingly though, no close links between carp biomass and aquatic health parameters, such as native fish diversity, aquatic vegetation or bank stability have been found, suggesting, he says, a few possibilities. It may indicate, for example, that the aquatic ecosystem components that persist today are those that are the least sensitive to carp presence. It is not an unexpected finding given these fish and plants survived the worst period of the carp invasion in the 1980s.

"Also, it is possible that perhaps carp may not be the environmental villain we perceive them to be and other factors may be the cause of poor ecosystem health," Dean Gilligan says. "Or we may need to reduce carp densities to a much lower level than even the lowest we have observed in the catchment in order to see any environmental response."

To do this, his team has installed carp exclosures at three sites in the catchment to assess the impact of carp on aquatic vegetation, benthic macro-invertebrates and native fish. By excluding carp from certain areas, Dean Gilligan aims to quantify the expected rate of ecosystem recovery and to provide a visible focal point for demonstrating carp control to the community.

Work to exclude adult carp from Lake Brewster and Lake Cargelligo will also start this year. It will trap carp moving towards and out of these wetlands, remove existing carp in these two locations using commercial fishing gear, remove migrating carp in the river channel using fishway traps, and promote recreational harvests through community fishing competitions. And with more than 3000 tagged carp in the Lachlan Catchment, Dean Gilligan says the effectiveness and cost efficiency of each control technique can be assessed. Freshwater program leader Wayne Fulton says CRC-funded research into carp control measures could prove valuable in eradicating the pest in the catchment.

Although interest has been piqued by pheromone work, other 'blue sky' measures, such as daughterless carp technology (where carp are genetically modified to only produce male offspring) and the koi herpes virus (a fatal disease which could be released to control carp) are in the development stage with the CRC. They could also prove to be longer term control measures.

The continuing drought has helped contain carp populations, but researchers are still hoping for further government funding to let them install more cages before any large rainfall events.

Carp segregation cages were trialled at Lake Brewster by SARDI, Lachlan CMA and State Water in 2007 and NSW DPI's Aquatic Ecosystems Unit is now trialling a William's carp separation cage.

It traps carp within fishways and has the potential to be of value to commercial fishermen, who can sell fish for a variety of products including pet food and fertiliser.

The cage works because migrating carp tend to jump out of the water when faced with a barrier, something native species usually do not do. It encourages carp to jump into a holding cage, allowing native fish to pass through. Preliminary data from the Murray River suggests that these fishway traps can remove 88 per cent of migrating carp from the river.

Working with State Water, which owns and maintains the trial trap location at Island Creek Weir, east of Condobolin in central NSW, the trial will run until at least mid-2010. The trap is designed to hold up to 500 kilograms of carp and during the warmer months, which are peak time for carp movement, the trap may need to be emptied up to twice a week.

On another front, the project also seeks to engage the public about research and management activities, what carp do to their river systems and how they can help.

LCMA catchment officer Michelle Jefferies oversees the CMA's involvement in the project from Hillston and is responsible for many of the campaign's 'grassroots' activities, such as organising carp fishing competitions and working with the NSW DPI to take to the public the specially designed River Revival display trailer.

She says people can be confused about carp and their impact. "People often assume carp are just big goldfish, but we put what is sold as a goldfish in the tank to show the difference and then people realise we are talking about different kinds of fish," she says.

The trailer is fitted with three fish tanks filled with a selection of species found in catchment waterways. One of the star performers is a particularly large carp named Colin. The trailer also displays information on fish species and has a television to show DVDs about carp impact.

Local fishermen are encouraged to report catches of tagged carp to help with the monitoring and in return they receive a gift for providing the project team with valuable catch data.

The CMA is also working with the Forbes based Lachlan Aboriginal Natural Resource Management Group (LANRMG) and the Lake Cargelligo Wetlands Committee to establish viability of carp harvesting by local indigenous people.

* It is hoped funding for the River Revival Lachlan River Carp Cleanup will be ongoing and allow carp removal programs to continue until 2035, when stakeholders suggest much more suitable native tenants will have moved back in.

More information www.invasiveanimalscrc.com.au
Michelle Jefferies T 02 6967 2897 E michelle.jefferies@cma.nsw.gov.au

To report captures of tagged fish 1800 185 027 or go to www.dpi.nsw.gov.au/fisheries/forms/fw-fish-tagging

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West Australian grower Clancy Michael is a lupin enthusiast.

He can grow the legume just fine – in fact, he enjoys growing them and considers them instrumental in his cropping program on his 4700 hectares of sand plain country at Mingenew – but he says the true potential of the lupin is unrealised.

Reflecting on last year's 12th Annual International Lupin Conference, held in WA, at which he was a presenter, Clancy says the opportunities for lupins as a major protein source for human, aquaculture and animal consumption is under rated. The challenge for Australian farmers, like himself he says, is being able to grow five million tonnes of lupins to develop critical mass to be recognised as a continuously tradeable commodity on the world's grain markets.

"It's the old chicken and egg scenario," he says. "At present we don't have the tonnage to develop new markets and guarantee continuous supply. But at the same time the lack of competitive demand for the existing lupins produced has not generated reason enough for farmers to want to grow more."

Last year Australia produced under half a million tonnes of lupins and 40,000 tonnes of albus lupins (suitable for human consumption and targeted at Middle East markets), according to Pulse Australia's Australian Pulse Crop Forecast.

One of the answers posed to the Perth conference by Clancy was using genetic technology – as has been applied to canola – to improve the versatility of lupins and increase their attractiveness to growers.

"Lupins as a plant are well suited to be manipulated by gene technology so improved consumer and production traits could be used to increase the production and global consumption of lupins," he says.

"This technology could also be used to strengthen the already natural comparative advantages lupins can have over other protein crops such as soya beans."

A glyphosate tolerant lupin, or Roundup Ready lupin, would have a great impact on Australian agriculture, according to Clancy, who believes growers would then have a choice of canola or lupins in challenging weed situations while potentially deriving larger nitrogen fixing benefits from lupins.

To avoid affecting Roundup's efficiency Clancy expects he would continue with Triazine Tolerant (TT) canola varieties to maintain weed control options.

Clancy's hope is fior increased lupin tonnages that would allow the crop to compete with soybeans, which in some countries already have the benefits of genetic modification.

On his farm at Mingenew, which he runs with son Daniel, Clancy sows 4500 hectares each year. Depending on paddock histories and weed challenges, wheat makes up 50 to 70 per cent of the program and the balance is divided between TT canola varieties and Mandelup lupins. Average annual rainfall is 445mm with generally 300-350mm falling during the growing season. In 2008 growing season it was 250mm.

Decisions on the most suitable crop are made depending on paddock soil type and moisture availability at the break of the season – much of which doesn't handle wheat on wheat.

"We'd like to be able to consider lupins a crop that stands alone in terms of its value, but the majority of WA growers have to look at its value to the rotation because for many people it's not worth growing when judged on its one year performance," Clancy says.

With a state average lupin yield of 1.2 tonne/hectare or less, the Michaels consider that with their lupin yields exceeding 2t/ha they can achieve reasonable profitability in average rainfall years This makes it easier for them to keep lupins in the rotation.

"While it is hard to quantify, the impact of the lupins on the following year's wheat crop yields is between 0.4 and 0.8t/ha," Clancy says.

"It is also generally believed, though I am not able to quantify, that a wheat crop following lupins achieves higher protein and better quality specifications."

Clancy feels these benefits are derived from the wheat crop being able to access organic nitrogen, built up by the previous lupin crop, which "sits in the background" waiting to be drawn on if the crop needs it.

"We are growing crops in soil with a low carbon level. Organic material is down to one per cent or less which can be an advantage or a disadvantage," says Clancy, who likens the situation to hydroponic farming, where the sand is the holding material for the plant, with nutrients and moisture added to grow a crop.

"If the wheat plant goes through a period of nitrogen deficiency then that background nitrogen left by the lupins seems to give it a better chance of riding the bumps."

Another attraction to the Michaels for lupins is they can be grown using the same sowing and harvesting equipment as wheat, with little change to calibrations and set up.

The lupins are sown on 25 centimetre row spacing's into the previous wheat stubble rows. A tine creates a water holding 10 centimetre furrow, into which the seed is placed at one to three centimetres depending on moisture availability, at a seeding rate of 60 to 120kgs/ha. Press wheels are then used to create good soil to seed contact and to avoid high winds blowing the furrows over.

In the crop's lifetime Clancy adds between 15 to 21 units of phosphorus – 25 per cent of which is added at sowing as starter P and the remainder broadcast before the growing season. Manganese and potash are also added, according to the results of soil tests. Lupins are responsive to phosphorus even though they don't use all the applied P.

"Phosphorus is leachable in high rainfall events in our soils so there is no point wasting it," he says. Last year the fertiliser cost worked out at $80 a hectare – which Clancy considers of value because there is residual nutrient left over for the following wheat crop.

More information: Clancy Michael T 0428 281 115.

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