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Studying sensory systems of fruit flies, worms a stroke of genius

Elissa Hallem, UCLA's fourth MacArthur fellow. Photos, video courtesy of the John D. and Catherine T. MacArthur Foundation.
When neurobiologist Elissa Hallem got an email from the John D. and Catherine T. MacArthur Foundation over a month ago, she thought for a second it was spam and almost deleted it.
The foundation had been trying unsuccessfully to reach her by phone at her lab in UCLA’s Molecular Biology Research building. She needed to call, the email requested, and not mention this to anyone. Puzzled, she looked up the organization online to "try to figure out, ‘What did I do now?’ I was completely confused."
What Hallem had done was score one of the most prestigious, no-strings-attached awards available, a prize for which it’s impossible to apply or compete, since the nomination process is shrouded in secrecy.
Last month, Hallem joined 22 other 2012 MacArthur Fellows, including conceptual photographer and UCLA alumna Uta Barth, chosen for their extraordinary creativity, originality and potential to make significant contributions in the future in such divergent endeavors as journalism, marine ecology, optical physics, violin bow-making, pediatric neurosurgery, fiction writing and geochemistry.
"It was the farthest thing from my mind," recalled Hallem of the moment when it became clear to her what the phone call was all about.
The MacArthur Fellowships, nicknamed the "genius" grants, come with $500,000 and a guarantee that the winners do not have to file a single report or publish one word to receive their sizable checks, spread over five years.
What she most appreciated, said Hallem, an assistant professor in UCLA’s Department of Microbiology, Immunology and Molecular Genetics, was that "it’s awarded not just for your past work but as an investment in your future … which, I think, makes it really nice."
Hallem has spent her relatively young research career — she finished a five-year postdoctoral fellowship at Caltech in 2010 — pursuing fundamental questions about how worms and other organisms respond to their environment on a molecular level. Her approach is so unique — combining genetics, neurobiology and behavioral studies — that in 2011, she was awarded a Sloan Research Fellowship, given to "the very brightest rising stars of this generation of scholars," noted Sloan Foundation officials.
Elissa Hallem 2-prv
Hallem is working on determining how parasitic worms that live in the soil and enter the human body by penetrating feet pick up chemosensory cues that help them find their hosts.
While a graduate student at Yale, Hallem became interested in understanding why fruit flies, which use their antennae to smell, are attracted to some odors and not others. She worked with a fruit fly genetically altered to lack odor receptors in one particular type of neuron in its antenna. "Basically, it had an empty neuron that couldn’t respond to any odors," Hallem explained. "So we could put an odor receptor in there and then test whether the neuron responded."
Using chemical compounds found in rotting fruit — a fruit fly’s favorite meal —Hallem tested how the odor receptors responded to more than 100 different odors found in nature. "Some neurons are excited by odors and others inhibited by them. It wasn’t clear when we started this whether this had to do with some property of the neuron or the odor receptor. We found that this was the property of the receptor, not the neuron."
Hallem next took her work in another direction: She found that she could put a mosquito odor receptor in the empty neuron of the genetically altered fruit fly. After testing two mosquito receptors, she discovered that one of them responded to an odor that is present in human sweat. Her Ph.D. thesis on this research has since been followed up by another graduate student who completed a large-scale analysis of mosquito odor receptors. Other grad students have since done field studies, Hallem said, "to show that some of these compounds can be effective when used in traps." A more effective trap could someday reduce cases of malaria.
Her work with insects has since steered her toward parasite nematodes or worms, specifically to the question of why free-living worms and parasitic worms, which have similar nervous systems, behave so differently. She’s testing the free-living worm C. elegans and multiple species of insect-parasitic worms and skin-penetrating, mammalian-parasitic worms, including one that lives in the soil in tropical regions and poses a major health risk in developing nations. By penetrating the skin of the foot, this parasitic worm can cause a debilitating infection, cognitive impairment in children and even death. And while there are drugs to treat this, the worms are developing resistance.
These parasitic worms use chemosensory cues to find their hosts. However, Hallem explained, "virtually nothing is known about how they respond to odors and how they detect humans. So we’re trying to figure out what they’re sensing and how they are sensing it." If she can identify the chemical compounds that attract these worms to humans, these compounds might be useful in a trap.
While Hallem is still pondering what research project she will take on with the MacArthur funding, she’s intrigued by the question of how insect-parasitic worms might alter neurocircuits to change the behavior of their hosts, fruit flies. "That’s something we’re considering studying," she said.
Science was an easy career choice for Hallem, a Santa Monica native, mother of two girls and wife to a Google software engineer. Her dad, a computer programmer with a Ph.D. in chemistry, shared his fascination with biology with his young daughter. "He would tell me about interesting things he had read in Scientific American, and I’d cut out the articles." Her mother, an attorney, proved equally supportive.
As an eighth grader, Hallem enrolled in a summer program sponsored by Johns Hopkins University’s Center for Talented Youth and offered locally at Loyola Marymount University. One course, in psychology, "had a little unit on neuroscience and mentioned molecular neuroscience," she recalled. "I just thought, ‘What could be more interesting than understanding how the brain works?’"
In high school, her first introduction to fruit flies — Drosophila — came when she worked in the UCLA lab of S. Lawrence Zipursky, a professor of biological chemistry and a family friend. In Zipursky’s lab, which studies the visual system of the fruit fly, Hallem helped screen for fruit flies with mutations that affected the development of their visual system.
"It became clear to me that Drosophila was a powerful model system for understanding the genetic basis of behavior," Hallem said. With three years of lab work at UCLA behind her, Hallem enrolled in Williams College in Massachusetts, a small liberal arts college where undergrads are responsible for "doing all the research that essentially professors are not doing themselves," she said.
After graduating from Williams, then getting her Ph.D. from Yale and completing her postdoc at Caltech, Hallem consulted Zipursky for advice on her job search. He urged her to give UCLA a good look.
"It’s been amazing," Hallem said of the collaborative, supportive environment she has found here among her colleagues, thanks to UCLA’s diverse neuroscience community and the Department of Microbiology, Immunology and Molecular Genetics.
"It’s the perfect department for me because of the wide range of work going on here — there are people who are working on parasitology and people who are in molecular neuroscience. And since we’re doing both, it’s the perfect fit."
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