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Systems Biology Weathers the Storm

Last December, in the face of one of the worst winter storms in decades, the Institute for Systems Biology declared a snow day. Most researchers stayed home, and a calm stillness transcended the Institute’s three-story home overlooking Seattle’s snow-crested Lake Union.

by Elie Dolgin

Last December, in the face of one of the worst winter storms in decades, the Institute for Systems Biology declared a snow day. Most researchers stayed home, and a calm stillness transcended the Institute’s three-story home overlooking Seattle’s snow-crested Lake Union. Rows of stacked PCR machines sat unused, and the room full of mass spectrometry machines was silent—hardly the poster-image of systems biology.

Yet in a small, darkened room, behind a flimsy, light-blocking curtain, action was lurking: Red LED’s flashed, solenoid valves shuttered, and a rhythmic pulsing overpowered the slight hum of the machinery. Click, click, click. Click, click, click.

That morning, Lee Pang, a bioengineering postdoc in Nitin Baliga’s lab, failed to dig his car out of the snow. But from the comfort of his own home, he was still operating the microfluidics device remotely. Last year, Pang used a microfluidics platform in combination with a fluorescent reporter to model and quantify yeast’s response to changing glucose availability (Nature, 454:1119—22, 2008). Now, he is building a similar lab-on-a-chip for Halobacterium.

The clicking and dazzling light show indicated that the minute pneumatic pumps were working, but by the next day the experiment was all gunked up.

For the better part of two years, Pang has been gradually perfecting his tiny gadget to meet the demands of a microscopic halophilic archaeon. Tapping into one computer, Pang pumped in a few hundred Halobacterium cells, bathed them in a salty growth medium, and turned on the UV light. Operating a second computer, he then snapped pictures every couple of minutes to track their cell division. The clicking and dazzling light show indicated that the minute pneumatic pumps were working, and the images showed that the microbes were growing happily, anchored securely in their tiny chambers. But by the next day the experiment was all gunked up. The media had dried out, the salt had crystallized, nothing was flowing, and the cells were dying. Evidently, the pump was not running fast enough. “I had to terminate the experiment a little early,” says Pang, who came in a few days later after the snow had subsided to clean up the mess. “There are a couple of kinks to work out.”

Another problem is that the device’s minute growth chambers—just 200 x 70 x 3μ large—aren’t quite yet small enough to completely anchor the tiny 1μ Halobacterium cells firmly in place. The challenge is to let the media flow while preventing the cells from dancing around in order “to track Halobacterium from cell division to cell division on a single cell basis,” says Pang.

Once those hitches are all solved, though, Baliga and his colleagues plan to probe the microbe’s response to metals, including copper and zinc. This will feed back into the larger model, drive new hypotheses, open up new research avenues, and ultimately, Baliga hopes, permit safe, efficient, and predictive biological reengineering. “When I think of the whole thing we’ve done, it amazes me how far we’ve gone in seven or eight years,” he says. “[Reengineering] seems quite far off, but I think we’ll be surprised again.”

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