photo: © Natalia Weedy photography
It’s safe to say that most chemistry majors don’t envision becoming experts in dissecting mosquito throats, but that’s the position Emily Derbyshire found herself in when her postdoc project at Harvard Medical School took an unexpected turn. Derbyshire originally planned to study the biochemistry of malaria infection—research that was in line with her experience as an undergrad and graduate student. But by the time she started working in the lab of chemical biologist Jon Clardy, he had won a grant for a more biologically-oriented malaria study, and Derbyshire agreed to change course. “She said that [the project] would be great to work on, and she did a fabulous job,” he recalls.
Derbyshire, now a chemical biologist at Duke University, grew up in upstate New York and was the first person in her family to graduate from university, at Trinity College in Connecticut. Although she’d been interested in science as a child, she says, it wasn’t until her years as an undergraduate chemistry major that she got an idea that working in science “can be a job.”
After Derbyshire graduated in 2002, she moved to the University of California, Berkeley, for her PhD studies. She hadn’t taken many biology courses as an undergrad but was drawn to research with implications for human health, so she began working with biochemist Michael Marletta to study nitric oxide signaling, which plays a role in multiple brain and body functions.
Derbyshire focused on how nitric oxide activates guanylate cyclase, which is a “tough enzyme” to work on for several reasons, Marletta tells The Scientist. “When you’re operating on a complicated enzyme that isn’t the most stable to work with, and without a structure, it really requires somebody with a keen mind for experimental design, and that’s what [Derbyshire] had,” he says. She uncovered important details about the protein’s activation, which laid the groundwork for characterizing it as a two-step process.1
As she was wrapping up her PhD in 2008 and considering where to do her postdoc, Derbyshire gravitated toward malaria. “It was a problem that was not getting a lot of attention at the time,” despite its large human impact, she says. That’s what led her to dissecting mosquito throats in Clardy’s lab: the idea was to head off malaria when it first invades and transforms within a host’s liver cells, which the parasite needs to do in order to proliferate and move on to the next stage in its life cycle, infecting red blood cells. Derbyshire’s approach was to extract malaria parasites from the mosquitos and use them to infect cultured liver cells, which could then be used to screen potential drugs that would inhibit the parasites during their liver stage.2
Since beginning her own lab at Duke University in 2014, Derbyshire has continued to investigate compounds that might thwart liver-stage malaria,3 while also analyzing changes in gene expression and knocking out host genes to find out whether the parasite needs them to thrive.4 In science, she says, “they pay you to do this job that you love.”
References
- E.R. Derbyshire, M.A. Marletta, “Structure and regulation of soluble guanylate cyclase,” Annu Rev Biochem, 81:533–59, 2012.
- E.R. Derbyshire et al., “Liver-stage malaria parasites vulnerable to diverse chemical scaffolds,” PNAS, 109:8511–16, 2012.
- R. Raphemot et al., “Plasmodium PK9 inhibitors promote growth of liver-stage parasites,” Cell Chem Biol, doi:0.1016/j.chembiol.2018.11.003, 2018.
- D. Posfai et al., “Plasmodium parasite exploits host aquaporin-3 during liver stage malaria infection,” PLoS Pathog, 14:e1007057, 2018.