YSM Issue 96.2

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FOCUS Public Health FATAL ATTRACTION Using fly pheromones against disease A natural tsetse fly odorant could help prevent African sleeping sickness BY CINDY MEI ART BY COURT JOHNSON From evoking long-forgotten memories through nostalgic scents to detecting imminent danger through noxious odors, smells hold undeniable power. Our sense of smell has served as a prime mechanism for survival since the beginning of time. Much of the work in the lab of John Carlson, a Yale professor of Molecular, Cellular, and Developmental Biology, is dedicated to studying the intricate mechanisms of Drosophila (fruit fly) olfaction: how do these insects detect and behave in the presence of volatile pheromones? An example of chemosensation, these pungent odorants—chemical compounds that have a smell—produced by organisms facilitate sexual attraction and mating by affecting behavior. The lab is interested in studying chemosensation as a method to control populations of insects that spread disease—such as the tsetse flies, insects that are responsible for spreading African trypanosomes, the causative agents of African sleeping sickness in Sub- Saharan regions. 22 Yale Scientific Magazine May 2023 www.yalescientific.org
Public Health FOCUS In a paper published in Science earlier this year, a team of researchers conducted a study to find natural odorants that may control the behavior of tsetse flies. Led by Shimaa Ebrahim, a postdoctoral researcher in the Carlson lab, the project was conducted in collaboration with Hany Dweck, an associate scientist in the Carlson lab, and Brian Weiss, a senior research scientist at the Yale School of Public Health. “I fell in love with the [tsetse fly],” Ebrahim, who studies the courtship behavior of Drosophila, said. Weiss echoed Ebrahim’s fascination, pointing out behaviors unique to the tsetse flies, such as the live birth and nurturing of their young, in contrast to the majority of insects, which lay eggs. Importantly, tsetse flies feed exclusively on vertebrate blood, leading to the transmission of Trypanosoma brucei (trypanosomes), a classification of protozoan parasites that cause African sleeping sickness and nagana in humans and domesticated animals, respectively. These diseases have devastating effects: nagana is responsible for an average loss of 4.5 billion dollars in resources every year in Africa. If left untreated, African sleeping sickness has a one hundred percent mortality rate. Unfortunately, access to treatment is not available everywhere. “Most of the drugs used to treat sleeping sickness are arsenic-based and horribly toxic. Very recently, there’s been some newly-developed medications, and they're much less toxic—but they’re much more expensive,” said Weiss, who studies tsetse flies and their associated microorganisms. To find alternative solutions, the researchers turned their attention to preventative measures. According to Weiss, the best solution to reduce fly populations is to use traps, as they are cheap and effective. However, not much is understood about the chemical signaling of tsetse flies, which may be key to luring the flies to traps. “If you want to control any insect that could cause disease or damage to any crop, you have to study their behavior to find the way to control this insect,” Ebrahim said. The Role Of Smell In Mating The researchers utilized the tsetse fly species Glossina morsitans. While Glossina fuscipes is the most abundant species in Kenya, they are difficult to rear in the insectary, according to Weiss. To examine possible odorants in sexual attraction, the researchers first studied tsetse fly mating behaviors. When paired together, G. morsitans males initiate mating with G. morsitans virgin females within seconds, and copulation continues on average for an hour. However, this reaction was not observed when G. morsitans males were paired with mated females, suggesting that there may be a difference in chemical signaling that results in the male’s behavioral responses. To determine whether differences in mating are driven by olfaction, pheromone extracts were obtained from the exoskeleton, also called the cuticle (the layer that covers the extracellular surface of the fly), of male and female flies that were soaked and gently shaken in hexane for ten minutes. Dummy tsetse flies made out of yarn were sprayed with these extracts and placed in a container with male G. morsitans, and a measure of attraction was determined by the percentage of males that initiated mating and stayed attached to the decoy flies for more than five minutes. However, the males were not attracted at all, suggesting that any odorants associated with mating are stored beyond the cuticles. After soaking another set of tsetse flies in hexane for twenty-four hours, it was observed that males were attracted sixty percent of the time to dummies sprayed with extracts from virgin females and twenty-seven percent of the time with extracts from mated females, with no response observed with male extracts. This observation indicates that there may be a difference in the composition of the extracts that made male flies more attracted to virgin than mated female G. morsitans. The longer soaking time may also explain why these compounds were not detected as potential pheromones in earlier research. The Discovery Of A Key Pheromone To determine if differences in compound composition were responsible for mating behaviors, the researchers obtained the chemical profile of the extractions via gas chromatography-mass spectrometry (GC- MS), which separates and detects different compounds. GC-MS identified three fatty acids and three fatty acid methyl esters that were not present in the ten-minute hexane immersion, which suggests the pheromones stored in internal glands may play a part in facilitating attraction. To test this hypothesis, the researchers repeated the previous experiment by spraying the dummy flies with each of these six compounds. They found that the male flies were strongly attracted to certain compounds that are present in higher levels in virgin females, such as methyl palmitoleate (MPO)—which attracted G. morsitans males eighty-seven percent of the time even when diluted—methyl oleate (MO), and methyl palmitate (MP). The www.yalescientific.org May 2023 Yale Scientific Magazine 23
Page 1 and 2: Yale Scientific THE NATION’S OLDE
Page 3 and 4: CONTENTS More articles online at ww
Page 5 and 6: The Editor-in-Chief Speaks THROUGH
Page 7 and 8: Physiology / Astronomy NEWS A NEW A
Page 9 and 10: Computer Science FOCUS TEACHING MAC
Page 11 and 12: Environmental Science FOCUS THE CAR
Page 13 and 14: Geochemistry FOCUS carbon dioxide d
Page 15 and 16: Medicine FOCUS PHOTOGRAPH COURTESY
Page 17 and 18: Dermatology FOCUS Bumps, whiteheads
Page 19 and 20: Ecology FOCUS ANIMALS AGAINST RISIN
Page 21: Ecology FOCUS to sediment depositio
Page 25 and 26: Environmental Engineering FEATURE S
Page 27 and 28: FEATURE Materials Engineering Astro
Page 29 and 30: Bioelectronics FEATURE stability, a
Page 31 and 32: Palaeogenomics FEATURE might have e
Page 33 and 34: Immunology FEATURE viruses, unlike
Page 35 and 36: ALUMNI PROFILE AMYMARIE BARTHOLOMEW
Page 37 and 38: THE DARKNESS MANIFESTO You’ve pro
Page 39 and 40: Wrought into a cycle, carbon schlep

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