Researchers at Trinity College Dublin are examining the shape of molecules to find new medical treatments for a range ofdiseases, writes Matt Egan.
Ever tried fixing a car engine with your eyes shut? It can be just as difficult to tackle a disease without first getting a look at what is causing it. According to scientists at Trinity College Dublin, this kind of "seeing" can be important in medicine. Using state-of-the-art technology, they can visualise how human diseases occur at a molecular level, and provide information that may help treat illnesses ranging from albinism to cancer.
"Pharmacists and other scientists who are developing treatments for diseases increasingly depend on being able to look at the molecules responsible," explains Dr Amir Khan, a protein crystallographer in Trinity's biochemistry department.
TCD is spending €2 million of a €30 million research budget to study the physical shape of biomolecules using X-ray crystallography.
Khan leads the structural analysis part of the work. His research partner, Dr David Lloyd, holds a Hitachi lectureship at Trinity and heads the molecular modelling aspect of the research.
It is particularly important that we can clearly visualise complex molecules called proteins because they do much of the work within our cells, says Khan. "Looking at protein molecules provides insights into genetic diseases that may lead to possible treatments or cures," he says.
"For example, the technique has helped scientists elsewhere develop HIV anti-protease inhibitors which have proved to be one of the more effective treatments in the fight against AIDS."
Inhibitors are specially shaped molecules that "switch-off" faulty protein parts. "Being able to see the molecule that is causing the problem helps scientist develop inhibitors that will block or shut down the malfunctioning part of a protein," he explains.
The team at Trinity is creating molecular images that are intended to shed light on a number of diseases. These include the genetic disorder possessed by some albinos, a rare but potentially lethal disease of the immune system called Griscelli disease. They are also looking at more common killers such as breast cancer.
In principle, Dr Khan's job may appear straightforward enough. "If you had to sum up what we do here, I'd say we look at big molecules at an atomic level in three dimensions."
In practice, however, it is far from simple and the technology required is highly sophisticated. The technology is necessary because even the world's strongest conventional microscopes are not powerful enough to view a single molecule in the kind of detail required here, says Khan. That is why molecular scientists like himself use a process called "X-ray crystallography" to deduce a molecule's shape.
"We produce a very focused X-ray beam and point it at a protein molecule. When it hits the protein, the X-ray diffracts - that is, it breaks up and scatters in different directions," he explains. Dr Kahn then measures these scattering X-ray beams while his colleague, Dr David Lloyd, uses the information to calculate the shape of the original molecule.
"By way of a comparison, think of drawn curtains with strong sunlight shining through the cracks," says Dr Khan. "If you studied the rays of light carefully enough you could work out the shape or outline of the curtain as it hangs over the window."
The technique is used by a number of research centres around the world, although Dr Kahn states that Trinity's work is "unique to Ireland".
It builds on research carried out in the 1960s. At that time, scientists found that if they accelerated tiny particles of matter to speeds approaching the speed of light, the particles sent out X-rays that provided clues about their structure. Unfortunately, there are relatively few particle accelerators in the world, as they consist of enormous magnetic rings that are often situated in underground tunnels.
Interest in X-ray crystallography grew more rapidly, according to Khan, when smaller in-house devices (such as Trinity's equipment) allowed scientists to conduct their work in their own labs. This technological breakthrough has since helped produce a number of medical advances.
The scientists at Trinity's biochemistry department also regard their work as part of the logical next step following the completion of the famous Human Genome Project which described the molecular structure of DNA, our genetic blueprint.
"Thanks to Genome, we now know what the human gene code is. Now we want to know what it does," says Khan
Dr Matt Egan is based at Glasgow's Medical Research Council Social and Public Health Sciences Unit. He is on placement at The Irish Times as a British Association for the Advancement of Science Media Fellow.