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Nicholas Buchler: The Dynamics of Regulatory Networks in Yeast

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Title: Assistant professor, Duke University
Education: PhD, University of Michigan, 2001
Recommended by: Hunt Willard, Duke University

Nicholas Buchler has made a career out of forging a marriage between his strengths as a theory-oriented biophysicist and his propensity for wet lab, curiosity-driven biology. While he says he'd always been interested in chemistry and physics, it was an introductory biochemistry and molecular biology course taught by Melvin Green at the University of California, San Diego, that got Buchler "hooked on biology."

While pursuing his doctorate degree in biophysics at the University of Michigan, he found himself "more and more attracted to ... [cellular] information flow and controlling the flow itself, and naturally, that took me to genes ... and the dynamics that genes can have," Buchler says. To that end, he found a postdoc position in Terry Hwa's lab at UCSD. And in 2003, Buchler, Hwa, and their colleague Ulrich Gerland published a PNAS paper in which they discussed schemes of combinatorial transcription logic in a quantitative bacterial model. In it, they report that transcription regulation appears to be "a 'programmable' computing machine." Then, it was during his second postdoc in Frederick Cross' molecular genetics lab at Rockefeller University that Buchler really "learned my wet-lab biology" in the yeast model organism, he says.

Now in his own lab at Duke University, Buchler is drawing from his interdisciplinary skill set to investigate the dynamics of regulatory networks in yeast. Among other projects, Buchler and his team aim to determine whether the mechanism behind sharp-switching responses occurs in natural systems and "if so, what sort of functional role it is playing," he says. "These very sharp threshold responses [are] quite important for generating interesting dynamics in gene networks."

According to Buchler, running an interdisciplinary lab has proven to be an especially rewarding challenge. "In my kind of research you've got some physics involved, and some modeling, and some theory, then in the same lab ... you're trying to do wet lab experiments," he says. "Most people don't come in with all-encompassing training. ... Everyone's coming at it with a different strength. And so it's been fun, but also a challenge."

Papers of note

Buchler regards his 2008 Journal of Molecular Biology paper, which he published along with co-author Matthieu Louis at the EMBL-CRG Systems Biology Unit in Barcelona, as one of his most notable to date. In it, he and Louis used mathematical and computational modeling to depict how molecular titration — a regulatory, protein sequestration mechanism — can generate ultrasensitivity in regulatory gene networks.

And the Nobel goes to ...

If he were to win, Buchler would want it to be for determining how cells sense environmental signals, process that information, and then compute it. "I would love to know the similarities between a neural system and a molecular system or an electronic system," he says.

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