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DIY Protein Microarrays

  • Title: Assistant Professor, Harvard University
  • Education: PhD, Harvard University, 2001
  • Recommended by: Ewan Birney and John Quackenbush

If a tool isn’t available off the shelf, some scientists will try to work with what’s on the market and simply accept its limitations. Martha Bulyk, on the other hand, would probably just invent her own — in fact, she’s already done just that. Bulyk, who is now an assistant professor of medicine, pathology, and health sciences and technology at Harvard, is using a unique microarray that she developed to study transcription factors. She hopes to put her findings to use to identify and predict not only binding site location, but transcription factor/DNA binding specificities across many species. “So there’s the identification of the sets of factors that are associated with the regulation of what sets of genes,” she says, “and then to understand [this], we also want to know where in the genome the DNA regulatory elements are through which of those transcription factors regulate gene expression.” 

Bulyk’s lab has developed a microarray-based approach to assay, on a large scale, many different transcription factor binding sites. This unique universal protein-binding microarray, or PBM, can probe every known 10-base-pair transcription factor binding site. In a paper published in November 2006 in Nature Biotechnology (“Compact, universal DNA microarrays to comprehensively determine transcription-factor binding site specificities”), she and her associates constructed the novel microarray and then used it to determine the binding sequence specificities for five transcription factors from yeast, worm, mouse, and human.

“We can use those sequences for all kinds of things,” she says. “We can try to understand the binding specificities of the transcription factors; we can use those sequences in genome scans to try to predict where the regulatory elements are in the genome; we can try to see whether there are particular sets of genes that are associated with some of those transcription factor binding site motifs.”

Bulyk double majored in biology and math at MIT, and then received her PhD in biophysics from Harvard, studying with George Church. She’s modeled her lab, which is currently made up of 14 people, after Church’s, which she credits with being “highly interdisciplinary.” Her staff does both experimental and computational work, and Bulyk spends a good amount of her time these days helping her staff members by “talking about their progress and together discussing the next experiments to do.”

As the field of gene regulation becomes more interdisciplinary and computationally based, one of the biggest challenges is finding people who are a good fit, according to Bulyk. Since a lot of the projects in her lab involve some sort of technology development and therefore “have been high risk/high payoff, not everyone is going to be suitable for that kind of project,” she says. The people who fit best either have a mixed background or are able and willing to communicate their needs to partners. “I don’t mean that every person in the lab has to be equally adapted to experimental and computational work, but has to have the interest and ability to appreciate, understand, and communicate with the people who are doing the other kind of work,” she says. 

Looking ahead

As for the field in general, she sees it moving toward increasingly interdisciplinary, team-based efforts where wet lab scientists and computational biologists have to work together to solve problems on a systems level. “I see it becoming more and more of a big science,” she says. “I also see a lot more automation coming in, and more and more technology development to increase throughput and drive costs down.”

And the Nobel goes to...

If she were to get the phone call about a certain coveted prize, Bulyk says she’d like to win it for “something in the area of gene regulation.”

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