Making waves at Marco Island

Elizabeth Cooney, February 24th, 2012
  • Shock waves travel under the ocean in this simulation showing
    ground wave action.
    Image courtesy of Marcus Thiebaux, Sciences Institute, USC

It’s been a long time since Chad Nusbaum has seen a conference room go so quiet so fast.

A speaker from Oxford Nanopore Technologies had just described the company’s new disposable device, which will sell for less than $900. The size of a USB memory stick, it reads individual chemical bases on a strand of DNA as it passes through a tiny hole, measuring differences in electrical conductivity to reveal their identity. A larger version of the device will stack in arrays that are projected to be able to sequence a human genome in 15 minutes.

“It sent shock waves through the meeting,” said Chad, who was part of a 30-strong Broad band attending the meeting in Marco Island, Florida. “People have been watching nanopore technology since the 1990s, and have accumulated a high level of skepticism over the years, so it is a game-changer if someone can go to the podium and say, ‘Yes, this works.’ ”

That someone was Clive Brown, whom Chad calls a “gearhead like us,” and the meeting was last week’s Advances in Genome Biology Technology conference. AGBT has grown from a niche gathering into a meeting that is a force in the field, bringing together researchers and technology developers in the rapidly changing sequencing world. Chad, one of the conference organizers, was joined by four Broadies presenting talks, Danielle Perrin, Michael Ross, Michael Zody (also an organizer), and David Jaffe, as well as 25 other Broad attendees.

The seismic Oxford Nanopore announcement underscores the rapid pace of innovation in sequencing-related technologies, including sample preparation before and computational analysis after sequencing. The way researchers and technology developers mingled at Marco Island mirrors the way Chad sees his job in the Broad’s Genome Sequencing and Analysis Program (GSAP), which is tightly linked to his counterpart Rob Nicol’s role in the Broad’s Genome Sequencing Platform (GSP). Chad works with vendors to guide technology development.

“Our collective goal is to get the best possible, most usable science-driving data,” Chad says.

Bruce Birren, who co-directs GSAP with Chad, says Chad’s group is always forward-looking.

“They think about way-out-there stuff that's still on the horizon,” he said. “They can think about what problems these technologies could be used to solve and how we match a new technology with important problems in the magic way the Broad does.”

Sometimes that means taking an idea to a technology company to find ways to answer pressing biological questions. Andreas Gnirke, director of GSAP’s molecular biology research and development, did that when he invented a method to pull out of a sample just what scientists wanted: the 1 percent of the genome that encodes proteins.

The simple idea was difficult to execute, but Agilent Technologies had one piece of the puzzle: long oligonucleotides, or stretches of DNA, that behave beautifully for this purpose. Andi, Alex Melnikov, and others developed the application, which was licensed to Agilent. Now it’s a tool that their colleagues, including Tarjei Mikkelson and Sheila Fisher at the Broad, have developed further. Tarjei’s tool dissects elements that control gene function and Sheila’s group has created high-throughput, sophisticated methods to automate Andi’s steps with robots.

“Here’s a technology that was enabling. I grabbed it to use for what we needed, and once it was here, other people could grab it for what they wanted,” Chad said.

That sequencing method also made a splash at AGBT – in 2008 (see story here.)

One can see this year’s AGBT breakout, Oxford Nanopore’s potentially transformative technology, as part of the continuing trend called the “democratization of sequencing.” Once the province of large centers because so much technical power was needed, sequencing now is dramatically faster and cheaper, lowering the barrier to entry in the field.

But sequencing at the Broad is more than machines, Chad says.

“What we do that other people are unable to do because of our concentrated expertise is the guiding of the technology, the development, its inventions,” he says. “It’s being able to take the risk with the over-the-horizon crazy technologies that if we look at ten of them, one is going to come in and really blow our doors off. But only if we work with developers over the next couple of years.”

Harnessing the power of genomic technologies serves one goal.

“The purpose of this technology isn’t to better technology,” Chad says. “It’s to better science.”