Sydney firm develops new DNA ID method

By Melissa Trudinger
Tuesday, 23 March, 2004

Sydney-based company Human Genetic Signatures (HGS) has developed a new method for identifying DNA methylation patterns -- an epigenetic phenomenon thought to play a role in ageing and disease.

Methylation of a particular gene usually signals that the gene has been turned off or silenced, while unmethylated genes are generally active. According to Dr George Miklos, the company's chief scientific officer, the methylation pattern across the genome can provide important information about the current state of a cell or tissue.

Cancer cells, for example, often show an increase in methylation of certain genes, said Miklos. "Our suite of technologies is fundamental for looking at what is happening at any different point in time in a human tissue," he said.

Miklos said that "methylomics" could be used to monitor the health of tissues, providing advanced warning of changes in gene expression that could lead to cancer or other conditions.

"Our suspicion is that the methylation pattern of our 30,000 or so genes will be different in every single tissue or cell type of the body," he said. "The methylation pattern is what defines what cell type it is, muscle, liver, heart and so on, and it is also the way that the cell uses to finely control what it will do."

HGS is working on several different aspects of methylomics, developing tools to more easily determine DNA methylation patterns, and correlating the methylation patterns from specific cell types with clinical and other data.

The company recently became a confirmation test site for Applied Biosystems to examine that company's new microarray platform, and subsequently to correlate gene expression with methylation patterns.

One major research program at HGS is examining methylation patterns in adult stem cells, with the aim of identifying changes to stem cells during the ageing process. Miklos said one practical application of this research could be to improve the quality of stem cells used in transplants.

The company is also about to release a kit for bisulphite modification. Typically, methylation patterns are determined by treating DNA with bisulphite, a process invented by HGS founder Geoffrey Grigg that converts unmethylated cytosines to an alternative nucleotide. But this method results in substantial losses of starting DNA and requires multiple steps. HGS says its modified technique for bisulphite modification can be performed in one tube, without loss of DNA.

The company is also utilising a proprietary technology involving intercalating nucleic acids (INA), which are fluorescent, nuclease-stable molecules that bind to DNA with high specificity. HGS licensed the INA technology from Danish company Unest, and also took 10 per cent equity in the company.

According to HGS product development manager Kerry Skellern, the MethylEasy kit will be launched at this month's American Association for Cancer Research meeting in Florida. The company is also working on more products including high throughput applications of the technology.

Miklos said the company aimed to develop open-source technology that could be picked up by researchers around the world. "But the value of genomic information is ultimately related to clinical outcomes," Miklos said.

HGS is working with US-based bioinformatics specialists Omicia, with the intention of eventually developing personalised medicine applications for methylomics utilising HGS technology and Omicia informatics capabilities.

A third partnership with US company Biotraces, which is developing exquisitely sensitive multi photon detection technology capable of measuring biomolecules present in very low concentrations, is also in the works.

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