Bulletin

Issue: September/October 2007

News

Scientists get close to malaria bug

The first pictures are back from a new X-ray approach directed by a La Trobe physicist to provide the high resolution images needed by biochemists and drug designers.

The pictures are providing close-up information about how a malaria parasite infects a blood cell and then causes it to stick to the walls of blood vessels. This vital biological work is one of the many projects that will benefit from the opening of the Australian Synchrotron.

First take on the close-up of the malaria parasite is an X-ray diffraction pattern that looks like a colourful fried egg, sunnyside up. The La Trobe work converts this into an image of a blood cell containing the malaria organism.

‘X-rays give the best resolution that we’ve seen for intact infected red blood cells,’ says biochemist Professor Leann Tilley, who has been working for twenty years on the parasite.

We can see the dimple in the red blood cell – coloured here in red – and a pink area that represents the thickest part of the cell’s structure. This is where the parasite has lodged.

If the scientists are able to fulfil their aim of increasing the resolution a further 50-fold, individual proteins involved in the parasite’s toxicity will be visualised.
‘The eventual outcome will be to get information about proteins for drug design,’ says Professor Tilley.

At present X-ray crystallography is used to study proteins at close quarters. Unfortunately, many don’t form crystals, including the vital G-protein coupled receptors which are involved in sensory perception and are targets for about 50 per cent of the drugs in use today.

The new X-ray imaging process is the first to come out of the Centre of Excellence for Coherent X-ray Science, a cross-disciplinary research centre with three of its key researchers located at La Trobe.

Physicist Associate Professor Andrew Peele, who leads a group of researchers at La Trobe and the University of Melbourne, has spent four years working with the algorithms and performing the necessary experiments to solve the imaging problems faced by biological researchers.

‘The malaria sample is a test case,’ he says. ‘We are very pleased with the result.’ The clear images of thin slices through cells made using electron microscopy are the result of seventy years of improvements, says the researcher. Our images are a terrific achievement in just four years
– and we can see inside whole cells. He aims to improve the algorithms and equipment so that Professor Tilley can look at the trafficking route of virulence proteins as they travel through the membrane of the host cell to hook onto blood vessels.

‘We are looking at ways to improve the data: stabilising the equipment, changing the wavelength and using different X-ray sources.’

The end product will be a synchrotronbased instrument that can image anything from biological samples to materials such as carbon nanotubes.

‘An important role of physicists in the 21st century is to engage with fundamental problems in the biological sciences.
‘This means we have to talk at a deep level with researchers outside our normal ken,’ says the physicist.

‘The malaria work is something people are very interested in and we are getting good feedback.

‘Talking about working on a cure for disease gets a much better response in the pub than a forty minute discourse on fundamental physics,’ he says.