This smells like it could reallybe important and even able to drive insects out of reach in general. That is very useful just about anywhere inthe wild. As pointed out, it is earlydays in terms of product, but product we shall have.
It appears that it chokes allreceptors and makes the environment unacceptable to the insects generally becausewe are taking advantage of a specific difference from animals.
It may also answer another not soobvious question. If mankind had alreadyemerged say thirty to forty thousand years ago, why would they have put up withmosquitoes at all? The answer is thatthey did not but were able to fully protect themselves by driving themaway. Wearing a ‘band of protection’ isa lot easier that actually driving a species to extinction which may well be impossible.
Released: 5/9/20119:00 AM EDT
Embargo expired: 5/9/20113:00 PM EDT
Source: Vanderbilt University
Newswise— NASHVILLE, Tenn. – Imagine an insect repellant that not only is thousands oftimes more effective than DEET – the active ingredient in most commercialmosquito repellants – but also works against all types of insects, includingflies, moths and ants.
Thatpossibility has been created by the discovery of a new class of insectrepellant made in the laboratory of Vanderbilt Professor of Biological Sciencesand Pharmacology Laurence Zwiebel and reported this week in the online EarlyEdition of the Proceedings of theNational Academy of Sciences.
“Itwasn’t something we set out to find,” said David Rinker, a graduate student whoperformed the study in collaboration with graduate student Gregory Pask andpost-doctoral fellow Patrick Jones. “It was an anomaly that we noticed in ourtests.”
Thetests were conducted as part of a major interdisciplinary research project todevelop new ways to control the spread of malaria by disrupting a mosquito’ssense of smell supported by the Grand Challenges in Global Health Initiativefunded by the Foundation for the NIH through a grant from the Bill &Melinda Gates Foundation.
“It’stoo soon to determine whether this specific compound can act as the basis of acommercial product,” Zwiebel cautioned. “But it is the first of its kind and,as such, can be used to develop other similar compounds that havecharacteristics appropriate for commercialization.”
Thediscovery of this new class of repellant is based on insights that scientistshave gained about the basic nature of the insect’s sense of smell in the lastfew 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 molecularlevel 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 theantennae of mosquitoes.
Whenthese receptors come into contact with smelly molecules, they trigger thenerves signaling the detection of specific odors.
In thelast few years, however, scientists have been surprised to learn that theolfactory system of mosquitoes and other insects is fundamentally different. Inthe insect system, conventional ORs do not act autonomously. Instead, they forma complex with a unique co-receptor (called Orco) that is also required todetect odorant molecules. ORs are spread all over the antennae and eachresponds to a different odor. To function, however, each OR must be connectedto an Orco.
“Think of an OR as a microphone that can detect a single frequency,” Zwiebelsaid. “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 microphonethat tells the brain when there is a signal. When a mosquito smells an odor, themicrophone tuned to that smell will turn “on” its Orco switch. The othermicrophones remain off. However, by stimulating Orco directly we can turn themall on at once. This would effectively overload the mosquito’s sense of smelland shut down her ability to find blood."
“Think of an OR as a microphone that can detect a single frequency,” Zwiebelsaid. “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 microphonethat tells the brain when there is a signal. When a mosquito smells an odor, themicrophone tuned to that smell will turn “on” its Orco switch. The othermicrophones remain off. However, by stimulating Orco directly we can turn themall on at once. This would effectively overload the mosquito’s sense of smelland shut down her ability to find blood."
Becausethe researchers couldn’t predict what chemicals might modulate OR-Orcocomplexes, they decided to “throw the kitchen sink” at the problem. Throughtheir affiliation with Vanderbilt’s Institute of Chemical Biology, they gainedaccess to Vanderbilt’s high throughput screening facility, a technologyintended for the drug discovery process, not for the screening of insect ORs.
Jonesused genetic engineering techniques to insert mosquito odorant receptors intothe human embryonic kidney cells used in the screening process. Rinker testedthese cells against a commercial library of 118,000 small molecules normallyused in drug development. They expected to find, and did find, a number ofcompounds that triggered a response in the conventional mosquito ORs they werescreening, but they were surprised to find one compound that consistentlytriggered OR-Orco complexes, leading them to conclude that they had discoveredthe first molecule that directly stimulates the Orco co-receptor. They havenamed the compound VUAA1.
Althoughit is not an odorant molecule, the researchers determined that VUAA1 activatesinsect OR-Orco complexes in a manner similar to a typical odorant molecule.Jones also verified that mosquitoes respond to exposure to VUAA1, a crucialstep in demonstrating that VUAA1 can affect a mosquito’s behavior.
“If acompound like VUAA1 can activate every mosquito OR at once, then it couldoverwhelm the insect’s sense of smell, creating a repellant effect akin tostepping onto an elevator with someone wearing too much perfume, except thiswould be far worse for the mosquito,” Jones said.
Theresearchers have just begun behavioral studies with the compound. Inpreliminary tests with mosquitoes, they have found that VUAA1 is thousands of timesmore effective than DEET.
Theyhave also established that the compound stimulates the OR-Orco complexes offlies, moths and ants. As a result, “VUAA1 opens the door for the developmentof an entirely new class of agents, which could be used not only to disruptdisease vectors, but also the nuisance insects in your backyard or theagricultural pests in your crops,” Jones said.
Manyquestions must be answered before VUAA1 can be considered for commercialapplications. Zwiebel’s team is currently working with researchers inVanderbilt’s Drug Discovery Program to pare away the parts of VUAA1 that don’tcontribute to its activity. Once that is done, they will begin testing itstoxicity.
VanderbiltUniversity has filed for a patent on this class of compounds and is talkingwith potential corporate licensees interested in incorporating them intocommercial products, with special focus on development of products to reducethe spread of malaria in the developing world.
VisitResearch News @ Vanderbilt for more research news from Vanderbilt.
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