Big money for protein study

A protein involved in the detection of the most lethal form of DNA damage and which is also linked with a rare genetic disorder has attracted the largest single slice of the NHMRC's latest project funding round for Queensland.

The protein, ATM, sits at the centre of a trio of projects headed by The Queensland Institute of Medical Research Prof Martin Lavin, which have collectively won grants worth $1.45 million, the largest sum allotted in the current round to any Queensland-based principal investigator.

The money will help a team of about 20 researchers probe the mysteries of this very large protein over the next few years.

The major grant -- of $775,000 -- will fund mouse model-based work on cancer susceptibility studies involving the disorder Ataxia-telangiectasia (A-T). Sufferers of the disorder, which typically leads to an early death by cancer, have a defective ATM gene. The same gene codes for the protein which provides the body with an early warning system for DNA damage. It is particularly sensitive in the detection of double strand breaks, the most lethal form of DNA damage, according to Dr Shaun Scott, who is handling the mouse model work.

The team believes that studying mouse models with defective genes may yield insights into the cancer risk of heterozygotes, he said.

A second grant -- of $435,000 -- will probe the activation mechanism of ATM in response to DNA damage, an area of work that will be overseen by Dr Sergei Kozlov. A third grant -- of $255,000 -- will underwrite research sparked by the discovery that some suspected A-T patients display perfectly normal ATM function.

The team member most involved with that area of the investigation, Dr Nuri Gueven, said cases of suspected A-T patients who display normal ATM were very rare in the general population.

But studying them could uncover yet unknown proteins, in the vicinity of ATM, which are affected in A-T-like disorders, he said.

By working out the mechanisms that ATM employs to identify DNA damage, the team may improve cancer therapies in general.

For example, "if we can identify what the mechanism is, we might be able to interfere with or inhibit the activator," Gueven said.

ATM also has the property of conferring radioresistance and A-T patients with defective genes are extremely radiosensitive. If ATM's mechanisms were better understood they might be applied to make tumour cells more radiosensitive, which could make given dosages of radiotherapy more effective in patients with other forms of cancer.

Although the A-T disorder affects only about one in every 100,000 of the population, research interest in ATM has increased steadily over the past 10 years, in step with recognition of its pivotal role in recognising DNA damage.

During that time, Prof Lavin has emerged as a primary worker in the field.

His success in winning NHMRC grant rounds has been fuelled by an impressive track-record of published articles in prestigious journals. In recent years, those have included Nature Genetics, Proceedings of the National Academy of Sciences USA , Cancer Research</>, and the Journal of Biological Chemistry.