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Shankar Balasubramanian to unveil tech that may hold key to ageing

Shankar Balasubramanian of Cambridge University helped to develop a new sequencing technique that looks at molecular changes to DNA


A British genetics pioneer who has won one of science’s most valuable prizes is poised to unveil a new technology that may transform our understanding of disease and ageing.

Professor Sir Shankar Balasubramanian was awarded a $1 million Breakthrough prize last week for helping to invent next-generation sequencing (NGS), an ultra-fast method of reading DNA that has revolutionized the life sciences.

NGS works by rapidly reading the four “letters” — A, C, T, and G — that form the backbone of our genetic code.

His biotech company, Cambridge Epigenetix, has developed a new sequencing technology, not yet on the market, that will read them more quickly and accurately than is possible at present.

“It’s clear that they are fundamental to biology, and also to disease biology,” he said. “We’re not far off from a world where, instead of whole-genome sequencing, we see whole genome and epigenome sequencing — at the same time, as a routine thing.”

One focus of epigenetic research is chemical entities known as methyl groups, which become attached to DNA and alter its identity. Adding a methyl group to the DNA letter “C” gives a new letter — “methyl-C”.

These epigenetic changes can act a little like volume switches, controlling the activity of individual genes. They appear to be closely linked to some diseases. Certain patterns of methyl groups becoming attached to a cell’s DNA are associated with cancer, for instance.

They also play a role in aging. As we grow older, the patterns of methyl groups attached to our DNA alter. By analyzing these changes, it is possible to estimate a cell’s “biological age”.

This raises a question: could we monitor and perhaps even modify our epigenetics to lead healthier, longer lives?

Balasubramanian says that Cambridge Epigenetix has developed a new sequencing technology that will simultaneously decode a person’s epigenetics and genetics.

“There’s now some hardened technology that will sequence the genetic letters and epigenetic letters at the same time — you can think of this as sort of a five-letter or six-letter sequencing technology,” he said.

Having readouts of a person’s epigenetics may provide early warnings of disease. “There’s already evidence that methylation [the addition of methyl groups to DNA] gives information about disease biology that can be useful,” he added.

Balasubramanian, who is a professor at the University of Cambridge, says he is regarded as something of a maverick thinker, but his work has already transformed genetics research. NGS, which he helped to create, has led to more than a million-fold increase in the speed at which DNA code can be read. It is a cornerstone of the rapidly growing field of personalized medicine, in which treatments are tailored to an individual’s DNA.

The first human genome was sequenced in 2000 after a decade of work that cost a billion dollars. Today a single machine using NGS technology can sequence 48 human genomes in 48 hours, at a cost of less than $1,000 each.

In 2007 Solexa, the company Balasubramanian co-founded to develop NGS, was sold for about $600 million.

“What we hope to empower people to do is to sequence the genetic letters and multiple epigenetic letters simultaneously. By doing so, you extract much more informational content from the DNA in your experiment or from your patients. I’m very excited about this,” Balasubramanian said.

“We do have a technology that I think will allow researchers who do conventional next-generation sequencing to do epigenetic information retrieval at the same time, without having to have a major shift in how they go about things . . . This technological capability will be made available to researchers very soon.”

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