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Genetic bug zapper
To prevent disease, scientists seek to keep mosquitoes from smelling
“We’ve reached an impasse in the fight against bad insects,” says Rockefeller’s Leslie Vosshall. “Insect-transmitted diseases take a large toll, but most insect repellents are based on trial and error, or folk remedies.”
New research from Vosshall’s Laboratory of Neurogenetics and Behavior, however, is bringing hard science to the design of the lowly bug spray. In a study published in the September 2 issue of Neuron,Vosshall and her coworkers have discovered that insects’ ability to detect odors — and people whom they can bite — depends on a single gene. Fruit flies lacking the gene, known as Or83b, lack the sense of smell.
Smell is very direct. In order for humans or fruit flies to smell bananas, for example, molecules from the fruit must waft through the air to specialized nerve cells that detect them. In humans these cells are at the top of the nasal passages. In the fruit fly they are located on the antennae and the maxillary palp, an appendage near the fly mouth. Odor-carrying molecules bind to receptors on brain cells, fitting like chemical keys into the locklike receptors, and set off a series of signals that the brain perceives as an odor.
A different gene codes for each kind of receptor, and the Or83b receptor is unusual in that nearly all the neurons that enable a fly to smell have it. Other kinds of receptors are divided up among small groups of olfactory neurons.
The Rockefeller researchers wanted to determine whether Or83b receptors detected only one or a few scents, or if they were general odor detectors that underlie the fly’s ability to smell any scent. In the second case, knocking out the gene would render the insects unable to detect — and bite — humans.
The scientists used a technique called gene targeting to create a strain of fruit flies lacking the Or83b gene. Then they tested the flies’ sense of smell by placing larvae one at a time in the middle of a Petri dish, with a drop of fruity-smelling ethyl acetate near the edge. Because normal fly larvae sense odors via an organ on the top of the larvae’s head, they crawl toward the smell. The mutant larvae, however wandered aimlessly in the dish. When the researchers administered a dose of the Or83b receptor, delivered to the odor-sensing cells through a sort of fruit fly gene therapy, the fly larvae were “cured” — like the normal larvae, they crawled toward odors.
To confirm that Or83b is necessary for sensing all odors,Vosshall and her colleagues also examined the larvae under a microscope, and found that in flies lacking Or83b receptors, the other smell receptors ended up in the wrong part of the nerve cells — in the body of the cell, instead of at the ends of the cell’s arm-like dendrites, where they would be exposed to odor molecules in the air. Finally, using a tiny electrode attached to the antenna of a fly, they tested whether nerve cells there were activated in the presence of odors. The results con- firmed their conclusion.
“For a fly to smell anything the Or83b receptor has to be present,” says Vosshall. “We still haven’t figured out how or why it works,” she adds. It could be that Or83b combines with other receptors to form different-shaped “locks” in which odorant molecules fit. Another possibility is that Or83b acts as a chaperone to direct other receptors to their proper placement in the cell. Or Or83b may be essential to the series of molecular signals that trigger perception of a scent.
Because the gene is found in a wide variety of insect species, repellents that block it, and thus prevent diseasecarrying insects from smelling and finding human hosts, might eventually help fight malaria and other infectious diseases.
“Insects are the primary vectors for malaria, dengue fever, yellow fever, and West Nile encephalitis, and they locate human hosts largely through their exquisitely sensitive olfactory systems,” says Vosshall. “In regions where these diseases are endemic, bed nets could be impregnated with a repellent that blunts a mosquito’s olfactory response. For backyard barbeques, you might have candles that release a repellent. Having different tools — repellents to ward off insects as well as drugs to fight the diseases they spread — will help us prevent disease.”

October 15, 2004



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