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Evolution of Signal Transduction

  • Title: Research Fellow, University of California, Berkeley; Visitor, Molecular Sciences Institute
  • Education: PhD, University of California, San Francisco, 2006
  • Recommended by: Roger Brent

Annie Tsong has a bit of an antiestablishment streak. Much of systems biology assumes that whatever can be measured matters, says Tsong, but she argues that that is just not the case. “I’d like to keep both the idea that something can be completely neutral — that it’s not adaptive and just free to float around in space because it doesn’t matter how they function — or that that they could be serving some kind of function,” she says.

At the Molecular Sciences Institute and the University of California, Berkeley, Tsong is working with Roger Brent and Michael Eisen to get a peek into the function and evolution of signal transduction. As part of the MSI’s Alpha project, which is delving into Saccharomyces cerevisiae’s signal transduction-mediated response to pheromones, Tsong has been studying quantitative aspects of signal transduction in multiple strains of yeast. Tsong’s other major interest lies in understanding subtle variation in evolution and how that affects an organism’s behavior and lifestyle.

Tsong’s bent for challenging the status quo was ingrained before she arrived at Berkeley. Much of it seems to stem from the influence of her undergraduate adviser, Harvard University’s Nancy Kleckner, whom Tsong describes as daring, original, and iconoclastic. “She’s not afraid to question what’s in the literature and to do the … most straightforward, the most elegant experiment to address that,” Tsong says. “She has a number of very daring papers that really overturned dogma.”

Tsong herself is not afraid to take new directions. “There’s just so much to do!” she says. “There’s not really a road map right now as to how to approach these questions that I’m interested in. I just have to make it up as I go along.”

Looking ahead

Tsong predicts a shake-up of preconceived ideas in biology, such as the current dualistic vision of protein regulation. “It is not just a matter of on/off, it’s how much on and how much off,” Tsong says. These characteristics, which may be critical to understanding a variety of human diseases, cannot be measured using current techniques. A key technological advance in this front would perform nearly instantaneous quantitative trait locus analysis to greatly speed up genotyping and analysis, she says. She also would like to see the incorporation of evolutionary and signal timing data into molecular biology.

Publications of note

As a graduate student at the University of California, San Francisco, Tsong wrote a 2003 Cell paper in which she and her colleagues figured out how mating type in Candida albicans is regulated. (Just a few years prior, biologists weren’t even sure that C. albicans mated.) Instead of using a negative regulator as S. cerevisiae does, C. albicans utilizes a positive regulator of mating type and then has the same pathway components as S. cerevisiae. When Tsong designed this experiment, she actually overdesigned it to include every possible permutation so that she and her colleagues had four or five times more data than they needed to reconstruct the pathway. “In this experiment, in this paper, it is probably the closest I think I’ll ever come to proving something,” she says.

And the Nobel goes to...

As no one can predict the whims of the Nobel committee, Tsong is just focusing on what interests her. “By the end of my career, I would love to understand how subtle changes in the genome can result in subtle changes in quantitative system output and how those can, in turn, result in major changes in organismal function,” she says.

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