Tuesday, May 10, 2011

On the Horizon: a Super Insect Repellant?

This story, about a possible new class of insect repellants a thousand times more effective than DEET, is interesting both for the possible result and what it shows about how science is now done:

The discovery of this new class of repellant is based on insights that scientists have gained about the basic nature of the insect's sense of smell in the last few years. Although the mosquito's olfactory system is housed in its antennae, 10 years ago biologists thought that it worked in the same way at the molecular level as it does in mammals. A family of special proteins called odorant receptors, or ORs, sits on the surface of nerve cells in the nose of mammals and in the antennae of mosquitoes. When these receptors come into contact with smelly molecules, they trigger the nerves signaling the detection of specific odors.

In the last few years, however, scientists have been surprised to learn that the olfactory system of mosquitoes and other insects is fundamentally different. In the insect system, conventional ORs do not act autonomously. Instead, they form a complex with a unique co-receptor (called Orco) that is also required to detect odorant molecules. ORs are spread all over the antennae and each responds to a different odor. To function, however, each OR must be connected to an Orco.

"Think of an OR as a microphone that can detect a single frequency," Zwiebel said. "On her antenna the mosquito has dozens of types of these microphones, each tuned to a specific frequency. Orco acts as the switch in each microphone that tells the brain when there is a signal. When a mosquito smells an odor, the microphone tuned to that smell will turn "on" its Orco switch. The other microphones remain off. However, by stimulating Orco directly we can turn them all on at once. This would effectively overload the mosquito's sense of smell and shut down her ability to find blood."

Because the researchers couldn't predict what chemicals might modulate OR-Orco complexes, they decided to "throw the kitchen sink" at the problem. Through their affiliation with Vanderbilt's Institute of Chemical Biology, they gained access to Vanderbilt's high throughput screening facility, a technology intended for the drug discovery process.

Jones used genetic engineering techniques to insert mosquito odorant receptors into the human embryonic kidney cells used in the screening process. Rinker tested these cells against a commercial library of 118,000 small molecules normally used in drug development. They expected to find, and did find, a number of compounds that triggered a response in the conventional mosquito ORs they were screening, but they were surprised to find one compound that consistently triggered OR-Orco complexes, leading them to conclude that they had discovered the first molecule that directly stimulates the Orco co-receptor. They have named the compound VUAA1.

If this molecule doesn't turn out to cause cancer or devastate fruit trees or something, those of us who have to work in swamps could be looking at a much nicer future.

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