Auckland student finds clue in mission to wipe out TB

By SIMON COLLINS science reporter

A protein molecule whose structure was identified by 25-year-old Auckland University student Nayden Koon has become a key clue in a worldwide search for a cure for tuberculosis.

Napier-born Mr Koon, one year into his doctoral research under Professor Ted Baker, says the protein looks like a perfect target for a drug because the bug that causes TB, mycobacterium tuberculosis, cannot live without it.

"It's a protein that doesn't exist in humans, so if anything were to be targeted against this protein, it wouldn't affect humans," he says.

Professor Baker, Mr Koon and about eight other staff and students at Auckland University are one of more than 70 groups in 12 countries who have been working for the past three years in an international non-profit consortium to beat TB.

The TB bug kills 3 million people a year, including four people in New Zealand last year.

"It kills more people than any other infectious disease," Professor Baker said.

"But until recently, the drug companies were not at all interested in TB because it was seen as being a Third World disease and they couldn't make very much money from those people.

"That's changing a bit because these days a large proportion of Aids patients actually die from TB, so TB is becoming a First World disease again, at least to some degree.

"They are not funding any of this research yet. But I suspect that if the preliminary work is done by academic groups, the most promising possibilities will be picked up."

Mycobacterium tuberculosis has about 3900 genes, about a tenth of the number in a human being. That means the bug is made up of potentially 3900 proteins, the complex molecules that make up living things.

Members of the TB consortium are gradually working out the structures of the proteins that look most promising as targets for potential drugs, listing what they are doing on the consortium website.

"There is no one to say that there shouldn't be any duplication, but the fact that you register your intention to work on that particular protein means that most other people will decide to do something else," Professor Baker said.

The work starts by cloning the gene that makes that protein and inserting it into another bug, Escherichia coli (E.coli), which then produces the same protein.

The protein is extracted and purified. It is then induced to form into crystals which can be seen in a microscope and contain millions of copies of the protein, all lined up.

The Auckland researchers can then work out the protein's structure either by an x-ray machine at Auckland University or by freezing the crystal in liquid nitrogen and sending it to a "synchrotron" - a $150 million facility that produces an extremely bright and focused beam of light.

In only a few hours late last year, the synchrotron at Brookhaven National Laboratory in New York was able to measure the data that Mr Koon needed. From this he was able to work out the structure of the protein.

Since then, he has been working out which parts of the structure have the key effects that make it essential to the TB bug.

The Auckland team and other New Zealand and Australian researchers who use some of the world's 43 or 44 synchrotrons met in Auckland last week to discuss the first Australasian synchrotron, being built by the Victorian Government in Melbourne.

At present, Professor Baker and his colleagues make about three trips every two years to synchrotrons in the US or Europe.

"Several people go from the lab and work 24 hours a day for three days and collect large amounts of data in a short time," he said. "Groups in the US and Europe tend to do most of their work at synchrotrons because they get more frequent access than we do."

He hopes the Melbourne facility will give New Zealanders much more regular access. But that may depend on the New Zealand Government contributing to the costs.

Since most of the world's synchrotrons are financed by governments, none of them charges the scientists for access, recognising the public value of groups such as the TB consortium.

Since the TB group was formed, other consortiums have started working co-operatively on problems such as malaria and viral proteins.

Once they understand the structure of proteins, they can do what is called "rational drug design" - designing drugs to act on particular protein structures, instead of trying thousands of potential drugs by trial and error.

Some of the work would probably be patented.

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