New source of inspiration for research

Brighter than the sun

The Australian Synchrotron is turning bright ideas into brilliant outcomes.

Australia’s biomedical and health researchers have a shiny new set of tools at their disposal at the Australian Synchrotron, the nation’s newest and brightest user facility.

From Alzheimer’s disease, anthrax and arthritis to leukaemia, malaria, Parkinson’s disease, tonsillitis, tuberculosis and flesh-eating bacteria, the Australian Synchrotron is helping researchers find the answers to some very challenging problems.

The properties of synchrotron light mean that experimental results are far superior in accuracy, clarity, specificity and timeliness to those obtained using conventional laboratory equipment.

“The synchrotron’s diverse imaging, spectroscopy and diffraction techniques are powered by x-ray and infrared light beams a million times brighter than the sun,” says synchrotron director Professor Robert Lamb.

“Since we officially opened for business in July 2007, the synchrotron has hosted more than 2000 visits by researchers from 48 Australian, New Zealand and overseas institutions keen to take advantage of our unique capabilities.”

Killer crystal structures

The malaria parasite kills more than one million people around the world each year, many of them children. It infects as many as half a billion people. A Monash University team working with researchers from the University of Technology Sydney and the University of Queensland recently laid the foundation for a new class of anti-malarial drugs. Using the synchrotron to obtain high-resolution crystal structures of a key enzyme in the malaria parasite’s digestive system, they showed that it was possible to block the enzyme’s action, effectively starving the parasite to death.

Tom Caradoc-Davies heads the macromolecular crystallography team at the Australian Synchrotron. Photo: Sandra Morrow.

Lower respiratory infections kill four million children a year. University of Melbourne researchers are using synchrotron x-ray crystallography to identify new strategies for dealing with drug-resistant Streptococcus pneumoniae, a major cause of these infections.

The synchrotron offers two specialised x-ray crystallography instruments. The high-throughput beamline is used for rapid high-resolution determination of large numbers of three-dimensional protein structures for drug development and medical studies. Researchers routinely use this beamline in their studies of disease organisms and health conditions such as extreme drug-resistant tuberculosis, anthrax, golden staph, arthritis, leukaemia and other inflammatory diseases, as well as potential bioterrorism agent Clostridium botulinum.

A second crystallography beamline is specifically designed to cater for very small crystals (less than 10 micrometres across or around one tenth the diameter of a human hair) and weakly diffracting crystals. A team from the Walter and Eliza Hall Institute took just half an hour to solve a structure that had previously eluded them for months. The work is part of their ongoing investigation into the fundamental mechanisms of cell apoptosis – also referred to as programmed cell death or the cell ‘suicide switch’. The University of Auckland is using the same beamline to study some unusual bacterial proteins that could become a target for next-generation antibiotics to treat diphtheria and Streptococcus pyogenes, which causes sore throats and tonsillitis and rheumatic fever but is more dramatically known for its role as ‘the flesh-eating bacteria’ behind necrotising fasciitis.

The crystallography beamlines are complemented by x-ray absorption spectroscopy, which is often used to help determine challenging protein structures. Only available at synchrotrons, this technique is widely used in the biological sciences.

Looking after the little things in life

An infrared microscope powered by synchrotron infrared light is also in high demand for analysing the chemical makeup of individual components just a few micrometres across. For example, Monash University researchers are using synchrotron infrared microscopy to examine the tiny chemical changes associated with the very early stages of diseases like multiple sclerosis. Synchrotron techniques are much more accurate and more sensitive than similar laboratory-based techniques. Monash University is also using the synchrotron to assist the development of methods for assessing single human egg cells for their viability for in-vitro fertilisation (IVF) procedures. University of Sydney researchers are investigating the mechanisms that underlie vanadium’s anti-diabetic properties.

Also in the micrometre range is an x-ray fluorescence microprobe with resolution down to 0.1 micrometres, which detects much lower concentrations of elements than other techniques such as proton-induced x-ray emission (PIXE). The microprobe provides information on elemental composition and location in a diverse array of biomedical and forensic samples. Researchers from the Garvan Institute and University of Sydney used the microprobe recently to investigate the possibility that highly-localised manganese imbalances might be linked to some forms of Parkinson’s disease, which affects up to 50,000 Australians, whose symptoms include uncontrollable shaking, muscle rigidity and slowness of movement.

The microprobe is complemented by a x-ray fluorescence nanoprobe, which offers sub-cellular elemental mapping and imaging. The University of Melbourne is using the nanoprobe to assist their ongoing efforts to understand key aspects of Alzheimer’s disease.

Combating cancer and helping babies breathe easier

Another futuristic use of synchrotron x-rays is a novel non-invasive test for breast cancer. This is based on an Australian discovery that scalp hair from breast cancer patients shows a unique diffraction pattern when examined by a synchrotron technique called small angle x-ray scattering (SAXS). The test has been commercialised by a Sydney-based medical research company, which conducts the tests on the SAXS beamline at the Australian Synchrotron. The SAXS beamline is also very useful for looking at the shape of large biological molecules, such as proteins, in solution and how they react with other compounds, such as drugs.

“Synchrotron x-rays are much more powerful than hospital x-rays and can be tuned to specific energy levels,” says Daniel Häusermann, principal scientist on the Australian Synchrotron’s imaging and medical beamline. “That makes them ideal for medical imaging techniques that show fine details of soft tissue as well as bones.”

The synchrotron’s upgraded x-ray imaging and medical beamline facility due for completion in 2012 will create non-destructive three-dimensional images of biological structures such as lungs, airways bones and teeth. The upgraded facility is keenly awaited by Australian researchers who currently have to use overseas synchrotrons for purposes such as developing new ways of helping premature babies breathe and assessing potential new treatments for cystic fibrosis.

The most advanced instrument of its type in the world, the imaging and medical beamline will also enable researchers to investigate a promising new radiotherapy technique called microbeam radiation therapy. This new technique uses an array of parallel synchrotron x-ray beams no wider than a human hair that kill tumour cells while causing less damage to normal healthy tissue than conventional radiotherapy.

The synchrotron’s versatile techniques are also applicable to many other fields outside the biomedical and health sector, including mineral processing, agriculture, food processing, advanced materials such as those found in computers and mobile phones, archaeology and art restoration.

Many hands make light source work

The heart of the synchrotron is its light source, lovingly tended by expert physicists and engineers. The light source consists of many pieces of highly complex equipment – electron gun, linear accelerator, booster ring, storage ring and so on – that combine to accelerate bunches of electrons to close to the speed of light and then use giant electromagnets to persuade them to move in a circular path. When electrons moving that fast travel round a bend, they emit extremely intense light: synchrotron light. The same phenomenon has been observed in interstellar space.

Apply here for enlightenment

Researchers from across Australia and New Zealand can apply to use the Australian Synchrotron through a merit-based, peer-reviewed system. Access is free if the results are published in the open literature, and successful applicants receive financial assistance towards travel and accommodation costs. The synchrotron offers approved users remote access to several of its beamlines, including the high-throughput macromolecular crystallography beamline.

Fee-paying clients can access the Australian Synchrotron’s facilities and additional support services on a confidential basis.

You can help shape our future

Located in the Melbourne suburb of Clayton, the Australian Synchrotron is funded by the Australian and Victorian Governments and a comprehensive array of medical and academic research organisations from across Australia and New Zealand.

With the facility’s initial set of nine beamlines almost complete, synchrotron managers have begun the process of planning for its future capabilities by talking to researchers around Australia and New Zealand about which new beamline facilities and other modifications would be most useful to synchrotron users.

The synchrotron is currently reviewing submissions made by groups of scientists who would like a particular synchrotron technique or techniques to be made available in Australia. If you would like to view the submissions, please visit the Australian Synchrotron website and search for ‘Australian Synchrotron Development Plan’.

More information: www.synchrotron.org.au