I
t’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.”gREFERENCES- E.R. Derbyshire, M.A. Marletta,
“Structure and regulation of soluble
guanylate cyclase,” Annu Rev
Biochem, 81:533–59, 2012. (cited
300 times) - E.R. Derbyshire et al., “Liver-stage
malaria parasites vulnerable to
diverse chemical scaff olds,” PNAS,
109:8511–16, 2012. (cited 89 times)
3. 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. (in press,
cited 0 times)
4. D. Posfai et al., “Plasmodium parasite
exploits host aquaporin-3 during liver
stage malaria infection,” PLoS Pathog,
14:e1007057, 2018. (cited 1 time)
SCIENTIST TO WATC HEmily Derbyshire: Malaria Hunter
© NATALIA WEEDY PHOTOGRAPHY
03.2019 |03.2019 | THE SCIENTIST THE SCIENTIST 53Assistant Professor, Chemistry and Molecular Genetics and Microbiology, Duke University, Age: 38IBY SHAWNA WILLIAMS