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Where Robots Rule

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By Steve Nadis

By now, anyone who follows genomics news knows that the MIT/Whitehead Institute Center for Genome Research has sequenced more bases (more than one billion) of the human genome than any other facility in the world.

Robots haven’t gotten much of the glory for that, but the center’s automation and development team, led by Kevin McKernan, thinks they deserve a mention.

For high-throughput sequencing, Whitehead has relied on a technique called solid phase reversible immobilization, which uses tiny magnetic beads to bind to DNA and separate molecules by size. Unlike conventional ways of isolating DNA, this method is amenable to automation.

Accordingly, Whitehead employs plate-track robots — a conveyor belt system designed and built by McKernan’s team to selectively pick out pieces of human DNA mass-produced in bacterial cells, scrub them, heat them, and label them with fluorescent tags.

The approach yields other benefits, in addition to time savings. Ten to 20 times less DNA is needed for sequencing than by conventional means because the DNA purity is higher and instrumentation more sensitive. Consumption of costly reagents, used to fluorescently label DNA segments, has also been cut 16-fold — enough to save tens of millions of dollars annually.

Once the DNA has been washed repeatedly and tagged, it is sent to sequencing machines that read 96 separate segments, each composed of 600 bases. Later this year, McKernan plans to redesign the entire pipeline to accommodate 384 rather than 96 strands of DNA, which will speed up the process by a factor of four. Farther down the road, he hopes to install a 1,536-read system to make things go even faster.

Some of the team’s technology, plus techniques for magnetically capturing and washing DNA, were adopted by another genome project center, Washington University. And others in the industry have shown interest. “After giving hundreds of tours of this lab to representatives of the biotech industry, I realized it made sense to spin out this technology to help overcome bottlenecks in DNA purification and isolation — traditionally the most time-consuming steps,” McKernan says.

So last July he helped found and became co-CSO for Agencourt Bioscience in Beverly, Mass. The company aims to commercialize the robotic DNA purification platforms.

Meanwhile, researchers at Whitehead and elsewhere are devising strategies for “sequencing organisms throughout the evolutionary chain,” as McKernan puts it, including the mouse, puffer fish, and other creatures. “Some say, why spend all the money? Our goal is to make it cheap enough to go ahead if you think there’s useful knowledge in that genome.”

As if that weren’t a big enough challenge, McKernan and his colleagues are trying to develop a pipeline to facilitate the study of the proteins made by all of the human genes. Studying the interactions of these proteins will be a huge effort, he says, “as big or maybe even bigger than the Human Genome Project itself.” Robots, inevitably, will be the unsung heroes.

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