Bulletin

Issue: May 2006

News

La Trobe sets up new laboratory into life and death research

La Trobe University now has a better claim than most Australian universities to be studying matters of life and death. That’s the whole focus of a rapidly expanding research group developing around Federation Fellow, Professor David Vaux.

Already researchers in three laboratories, working with mice, insects and yeast, are beavering away at several aspects of the nature of programmed cell death and its potential applications to human health.

Programmed cell death – or apoptosis – is now known to be just as important as cell division in the growth, development and defence of multicellular organisms. Every second about a million cells are produced by cell division in the human body, and about the same number commit suicide. If this didn’t happen, the cellular build-up would give rise to cancers.

However, if the suicide mechanism malfunctions and cells destroy themselves unnecessarily, it can increase the damage in heart attacks, strokes and nerve degeneration. So, knowledge of the process of apoptosis is critical to understanding human health, and is leading to the development of therapeutic drugs.

Professor Vaux is the man who initiated interest in cell death by finding the first molecular component of the apoptosis mechanism. He published his discovery in 1988 in the influential scientific journal Nature, in a paper that has become the most highly cited primary publication from Australia in the past twenty years. The field he opened up is now the subject of thousands of papers a year. In 2004, he was awarded the Victoria Prize for his efforts.

Earlier this year, Professor Vaux moved to La Trobe from the Walter and Eliza Hall Institute (WEHI) as a Federation Fellow. The fellowship scheme was originally established to entice successful researchers back to Australia. Federation Fellowships are now awarded to researchers within Australia, to encourage them to build up new centres of expertise. And that’s the reason why Professor Vaux was so interested in coming to La Trobe.

‘WEHI is full to bursting,’ he says. ‘At La Trobe, there is more space and loads of potential – and the core of researchers at the School of Molecular Sciences is world class.’

Although the University is committed to match the Federal Government’s funding of $250,000 a year for five years, Federation Fellows like Professor Vaux can help in the quest to recruit talented young researchers, build critical mass, and boost research ranking.

And that’s just what is happening. One of the attractions for Professor Vaux of coming to La Trobe was to be able to continue to work with Dr John Silke, who moved with him from WEHI. Dr Silke now has a tenured position and his own laboratory at the University, as does Dr Christine Hawkins who has come from the Murdoch Children’s Research Institute. Add to that two post-doctoral fellows, Drs Bernard Callus and James Vince, a senior research assistant from WEHI, Ms Diep Chau, three doctoral students and another three honours students, and you have the beginnings of a powerful research cluster.

Professor Vaux and Dr Silke head laboratories studying a family of cell death inhibitors known as inhibitors of apoptosis proteins (IAPs).

‘The first IAPs were found in viruses that affect insect cells,’ Professor Vaux says. ‘Viruses use cells to replicate, so cells often try to kill themselves in an altruistic attempt to stop viral replication.

But viruses have fought back by carrying cell death inhibitors, that help them create zombie cells so they have more time to replicate.’

The two researchers have concentrated on three mammal IAPs: cIAP1, cIAP2 and XIAP. They have knocked out the genes for XIAP in mice, and are now working on the genes for cIAP1 and 2 as well.

Because IAP genes seem to be turned on at high levels in a number of different human cancers, drug companies also are interested in IAPs. Stopping them from functioning could be a potent way of killing cancer cells. Professor Vaux and Dr Silke are working in collaboration with a US company that has produced potent inhibitors of IAPs.

Meanwhile, Dr Hawkins is using yeast to study both mammal and insect components of programmed cell death. Yeast has no apoptosis mechanism of its own, and so is useful as a ‘living test-tube’ for attempts to recreate the pathways.

Of the post-doctoral researchers, Dr Vince is looking at members of the tumour necrosis factor (TNF) superfamily of receptors, and Dr Callus is investigating how two of the key killer proteins initiate apoptosis. And, as if that wasn’t enough, Professor Vaux has begun another line of research involving cell death – in this case studying aging in honey bees (see above).