Tropical medicine goes molecular

Not everyone can make a machine able to explore the human genome and its vast network of DNA molecules; the frontier of ‘inner space’.

It is a comparatively new speciality, where the machines are as pioneering as they are functional in their probing of the human body’s inner cosmos.

These machines – DNA microarray scanners – make it possible to map this unfamiliar and information-rich space and scientists have invented a unique kind of cartography for the job.

Called comparative genomics, it links the human body – its formation, ancestry, and breakdown during disease – to the structure of discrete regions on DNA molecules (genes) and the hereditary information they emanate.

Like explorers of times past, genomics researchers too possess the potential to redraw the world – by forever changing our understanding and practise of medicine.

Until now the vast bulk of genome mapping has taken place in advanced economies, however, one of the few scientific equipment companies able to build one of these machines, US-based Agilent, recently formed a partnership with a medical school in Southeast Asia through its philanthropic arm, the Agilent Technologies Foundation.

The result is a new centre for human genome studies that is accessible to young Asian and African students to study diseases of regional importance, while also servicing researchers in the broader Asia region.

Called the Monash-Agilent Authorised Microarray Service Centre, it has been operational since late February 2012.

To meet its end of the bargain, Agilent provided its brand of ‘microarray’ scanner. The scanner allows genetic differences among vast numbers of people to be analysed for telltale molecular signals, in order to guide the development of new diagnostic tools and drug therapies.

Agilent's partner is the Jeffrey Cheah School of Medicine and Health Sciences, located near Kuala Lumpur in Malaysia, at the Monash University Sunway Campus in Selangor. Here all courses are taught in English due to Sunway’s affiliation with Monash University in Australia.

Astoundingly, the school is just five years old but was able to attract Agilent’s involvement by virtue of the extraordinary commitment to research from its staff and nearly 60 PhD students. This is in addition to training some 600 medical and 200 pharmacy students each year.

The deputy head of research and biomedical science, Professor Iekhsan Othman, says the school had been outsourcing its genome-scanning work for several years to technology providers like Agilent. Then the decision was made to invest in its own equipment for a genomics facility dedicated to biomedical research.

“At the medical school we keenly feel the need to have an impact and that underlies the rationale for establishing a strong research capacity. “Agilent proposed their technology to the school, a system that was found to suit the researchers’ needs well,” he says.

“The Agilent Foundation then donated the microarray scanner – the central piece of equipment for comparative genomics studies – and the company became involved in providing continuous technical support.”

The medical school uses genomics in two fundamental ways. There are projects to map changes in gene expression across the genome that occur in response to disease.

Then there are efforts to map genetic differences that distinguish Malaysians of different ancestry – primarily Malay, Chinese and Indian ethnicity. The school, in conjunction with neighbouring Asian countries Singapore, Thailand, Indonesia, India, and Japan are using the ethnic biomarkers to trace ancient migration patterns across Asia.

In addition the two streams can intersect: “Staff are looking into the breast cancer genome, for instance, particularly as it relates to certain enzymes implicated in initiating cancer,” Professor Othman says.

“We can then use the microarray scanner to query the genome of large populations to understand why different ethnic groups in Malaysia have different breast cancer rates.”

Among the health concerns targeted for study at the Monash Campus are conditions also familiar in the West, such as obesity, cardiovascular disease, breast cancer and diabetes and how it leads to kidney failure.

There is also a strong focus on public health and infectious disease, especially from tropical viruses for which there are currently no vaccines or treatment such as dengue, SARS and H5N1 influenza (or bird flu).

Vaccine specialist Associate Professor Sharifah Binti Syed Hassan is mapping how genes respond when a virus infects a cell. These responses are then compared at the population level to identify biomarkers linked to variation in disease severity.

Clues can then be obtained about how the virus causes disease and which responses make the best candidates for the development of vaccines, diagnostics tests or therapies.

“For example, dengue is a big problem in Malaysia that currently relies on controlling the mosquito to prevent disease,” Associate Professor Sharifah Binti Syed Hassan says. “But we look at how the virus causes disease directly as there are still a lot of unanswered questions about many tropical viruses.”

Rod Minett, general manager of Agilent's Life Sciences Group in South Asia, Korea and the Pacific Region, says the agreement with Monash helps to cement Malaysia as a centre for life science research and development (R&D). The partnership is the first of its kind with a Malaysian university.

Agilent acquired its commitment to philanthropy from its parent company Hewlett-Packard, from which it spun-off in 1999. Coincidentally, its DNA microarray equipment uses similar technology to inkjet printer nozzles to imprint on to glass slides the many thousands of DNA probes needed to compare human DNA samples.

For Monash, the support it has received from Agilent has served to validate and invigorate its commitment to meeting local R&D needs.

In 2012, the University intends to purchase an electron microscope, build a new laboratory complex to accommodate 100 PhD students, and prepare to launch a new degree in medical sciences that feeds into the existing PhD program.

“These projects are important to the third world, to countries that have the same problems we face in Malaysia,” Professor Othman says.