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Divining the scent of a human: for mosquito, it’s a molecular event

Yale Medicine Magazine, 2004 - Spring


To most people perspiration ranks low on lists of attractive features, but one creature finds the smell of human sweat irresistible: the female of Anopheles gambiae, commonly known as the mosquito. Just what makes our perspiration so alluring to this ruthless predator is a question that intrigues not only the companies that make insect repellents and the people who use them, but most of all the epidemiologists trying to reduce the toll of mosquito-borne diseases.

Now scientific research is beginning to reveal an answer. John R. Carlson, Ph.D., professor of molecular, cellular and developmental biology, Elissa Hallem, a graduate student in the Interdepartmental Neuroscience Program, and colleagues have developed a transgenic technique that allows them to identify the functions of specific odor receptors in the mosquito antenna. Their paper, published in the January 15 issue of Nature, describes how the researchers pinpointed the receptor gene, AgOr1, and the compound to which this receptor responds, the odorous molecule 4-methylphenol.

The scientists used a “knockout” fruit fly lacking one if its odor-receptor genes. They substituted the mosquito gene AgOr1 and then measured the animal’s response to various odors; the only molecule to produce a strong response was 4-methylphenol. A similar gene, AgOr2, used as a control, showed no such response. This observation, together with previous findings that AgOr1 is present only in female mosquitoes and that the expression of this gene tends to diminish after the mosquito has had a blood meal, suggests that the AgOr1 receptor plays an important role in the mosquito’s hunting and feeding behavior.

According to Carlson, this work puts researchers “on the right track” toward developing a truly effective mosquito repellent. “If we can find each of the odor receptors and identify the specific compounds they’re responding to, the next step would be to come up with inhibitor or blocker compounds, which would bind to the receptors but not activate them,” he explains. The mosquito would thus be unable to perceive the odors that normally lead it to a human banquet. Large numbers of people might be protected from bites, or from life-threatening infections. (The mosquito-borne disease malaria kills an estimated one million people each year, most of them children.)

The research on odor receptors may also have a direct application in insect control: the odors most attractive to mosquitoes could be used to lure the insects away from human populations and into traps where they could be destroyed. In principle, says Carlson, the same techniques might even be used against crop pests. But he cautions that “the system we have created, a system that can identify odor-receptor genes, has not yet been applied in other insects.” With the work on mosquitoes yielding such promising results, progress on dealing with other insects is probably not far behind.

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