SCIENTIST TO WATCH

Helen Blackwell: The Accidental Microbiologist

Jun 1, 2006
Jeffrey M. Perkel
<figcaption> Credit: © JASON VARNEY | http://www.VARNEYPHOTO.COMVARNEYPHOTO.COM</figcaption>
Credit: © JASON VARNEY | http://www.VARNEYPHOTO.COMVARNEYPHOTO.COM

When facing the unknown, Helen Blackwell dives in without hesitation. At least three times thus far in her scientific career her work has taken her into unfamiliar territory, from organic chemistry, to chemical biology, to plant biology, to microbiology. And where sink or swim is the imperative, Blackwell sets an enviable pace.

Blackwell earned her doctorate in organic chemistry at the California Institute of Technology. While finishing a thesis on olefin metathesis (a reaction that stitches together carbon-carbon double bonds),1 Blackwell pondered a move into biology. "I became very interested in making molecules that did things," she says, and so in 1999 she joined Stuart Schreiber's lab at Harvard University.

Schreiber's team was using chemical genetics to probe developmental pathways in classical animal models such as Caenorhabditis elegans and zebrafish. Blackwell chose to work with plants, a system unexplored in the lab. "Plants have really amazing ways of sensing their environments," she says. They respond to light, temperature, and microbial invasion, often through small molecules. "I wanted to start studying, from an organic chemist's point of view, how these compounds function in a biological context in plants."

Blackwell's identification of several small-molecule sirtuin inhibitors in Arabidopsis2 taught her the value of combinatorial chemistry for chemical biology, she says. "But in my own lab I think I wanted to take a different angle on it, because what I saw was that it was taking a huge amount of time to make these libraries."

Blackwell's angle: microwave-assisted chemistry.3 With microwaves, she says, "you can get instantaneous heating and very fast reaction rates" - up to 1,000-fold faster than by traditional methods. "We can make a library of 100 to 200 compounds in a day, routinely."

Title: Assistant professor of chemistry, University of Wisconsin, Madison
Age: 34
Representative Publications:
1. H.E. Blackwell et al., "New approaches to olefin cross-metathesis," J Am Chem Soc, 122:58-71, 2000. (Cited in 141 papers) 2. C.M. Grozinger et al., "Identification of a class of small molecule inhibitors of the sirtuin family of NAD-dependent deacetylases by phenotypic screening," J Biol Chem, 276:38837-43, 2001. (Cited in 80 papers) 3. H.E. Blackwell, "Out of the oil bath and into the oven - microwave-assisted combinatorial chemistry heats up," Org Biomol Chem, 1:1251-5, 2003. (Cited in 63 papers)

Now, Blackwell is applying that chemical dexterity to bacterial communication, looking for molecules that can interfere with quorum sensing and virulence in organisms such as Pseudomonas aeruginosa. Her lab has identified some 20 lead compounds so far.

Jo Handelsman, one of Blackwell's collaborators at Madison, calls Blackwell "a very successful example of a well-trained organic chemist who can think about the biological implications of her chemistry." Though undoubtedly aided by a stellar pedigree - her graduate advisor Bob Grubbs won a 2005 Nobel Prize - Blackwell continually distinguishes herself. Schreiber describes her as brilliant, creative, and fearless. "I have been running my lab for roughly 25 years, and there have been many exceptional young scientists come through," Schreiber says. "She pegged the meter."