La Trobe University biochemist, Dr Alexander Maier, has been shortlisted for one of Australia’s top scientific awards – the Eureka Prize.
The award judges say Dr Maier has made an enormous step forward in understanding a key adaptive strategy used by the malaria parasite to survive in – and cause damage to – its human host.
He has identified special proteins that help the parasites stick to, and replicate on the inner lining of blood vessels. If they didn’t stick they would normally be flushed to the spleen to be destroyed.
Working with ‘gene knock-out technology’, he has documented more than 30 genes essential for the parasite’s survival. These genes are now being targeted for potential new drugs to combat a disease that kills more than one million people every year, most of them children.
This ‘gene knock out’ approach – or ‘reverse genetics’ (you destroy a gene in the disease causing organism and then observe how that, in turn, affects its structure and chances of survival in the human body) – is helping him and his team study recently identified malaria proteins essential for forming protrusions, or ‘knobs’, on the outside of infected red blood cells.
These knobs are thought to be the site for ‘velcro-like’ hooks that keep malaria infected blood cells firmly attached to artery walls. It’s here that the cells turn into little replicating factories, churning out thousands more infectious malaria parasites which, when released, cause the cycles of chills and fevers so characteristic of the disease.
The obstruction of blood vessels also accounts for many other symptoms of malaria infection. By ‘switching off’ the parasite’s ability to form these knobs and hooks, Dr Maier says infected cells are swept by the blood stream to the spleen and eliminated before they get a chance to replicate in great numbers.
‘Hence we have a strong candidate mechanism for the action of possible new generation malaria drugs. With the number of effective anti-malarial drugs dwindling due to the spread of drug resistance, the demand for new safe and affordable interventions is higher than ever before.’
Dr Maier’s team of seven people at La Trobe’s main Melbourne campus works with other researchers in Europe, India and Africa. Their project – and potential drug design approaches based on other genes – is funded by the Australian Research Council and the National Health and Medical Research Council.
Dr Maier came to Australia from Germany ten years ago as a post-doctoral researcher at the Walter and Eliza Hall Institute. He joined La Trobe two years ago. He decided to stay in Melbourne because of Australia’s great reputation for malaria research.
The country punches far above its weight, he says. La Trobe alone has three groups tackling different aspects of the malaria problem; the other two are led by Professor Leann Tilley and Professor Robin Anders and Associate Professor Mick Foley. And there are groups at both Monash and Melbourne universities as well as at the Burnet and Hall Institutes.
Some of the earliest molecular malaria work was done at Melbourne’s Hall Institute, which generated the world’s first knock-out of a malaria gene. When Dr Maier came to Australia in 2000, he says there were less than ten known gene knock-outs. Since then, largely through work of the Hall Institute’s Functional Genomics Facility, which he headed for six years, Australia has added another 100.
‘Today there about 150 such knock-out cell lines recognised world wide – so more than three quarter of the work has been done in Australia,’ he says.
Plasmodium falciparum, the most dangerous of five known malaria causing parasites, has about 5,000 genes, compared with some 25,000 for a human being.
‘Malaria has been known for thousands of years,’ says Dr Maier. ‘It’s caused by a small single cell creature. Our human brain has billions of cells. Yet malaria still continues to out-smarten us!’
Dr Alexander Maier, tel: 03 9479 6563 / 1344; email: [email protected]