May 152011
 
Illustration showing the anatomy of a mosquito...

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Imagine an insect repellant that not only is thousands of times more effective than DEET — the active ingredient in most commercial mosquito repellants — but also works against all types of insects, including flies, moths and ants.

That possibility has been created by the discovery of a new class of insect repellant made in the laboratory of Vanderbilt Professor of Biological Sciences and Pharmacology Laurence Zwiebel and reported this week in the online Early Edition of the Proceedings of the National Academy of Sciences.

“It wasn’t something we set out to find,” said David Rinker, a graduate student who performed the study in collaboration with graduate student Gregory Pask and post-doctoral fellow Patrick Jones. “It was an anomaly that we noticed in our tests.”

The tests were conducted as part of a major interdisciplinary research project to develop new ways to control the spread of malaria by disrupting a mosquito’s sense of smell supported by the Grand Challenges in Global Health Initiative funded by the Foundation for the NIH through a grant from the Bill & Melinda Gates Foundation.

“It’s too soon to determine whether this specific compound can act as the basis of a commercial product,” Zwiebel cautioned. “But it is the first of its kind and, as such, can be used to develop other similar compounds that have characteristics appropriate for commercialization.”

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.”

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