Don't stop and smell the roses: "blinding" an insect's sense of smell may be the best repellent, according to research by Rockefeller University scientists.
"Pest insects have a profound negative impact on agriculture and human health," says Rockefeller University's Leslie Vosshall, Ph.D. "They are responsible for global losses of crops and stored agricultural products as well as the spread of many diseases."
In the heated battle between people and insect pests, Vosshall and colleagues, in collaboration with the biotech company Sentigen Biosciences, Inc., report in the February 22nd issue of Current Biology that an understanding of insects' sense of smell may finally give humans the upper hand.
The researchers studied four very different insect species: a benign insect favored by researchers, the fruit fly, which is attracted to rotting fruit, and three pest insects: the medfly, which is a citrus pest; the corn earworm moth, which damages corn, cotton and tomato crops; and the malaria mosquito, which targets humans. They found that one gene, shown to be responsible for the sense of smell in fruit flies, has the same function in these pest insects, which are separated by over 250 million years evolution
"While all these insects have sensitive olfactory systems, they all have very different smell preferences," says Vosshall, head of the Laboratory of Neurogenetics and Behavior. "Yet this odorant receptor is highly conserved across all of these different species."
Vosshall's laboratory previously published research demonstrating that out of 62 odorant receptors in the fruit fly, only a single one, named Or83b, was essential the sense of smell in fruit flies. When they removed the gene, the mutant flies couldn't smell a wide variety of different odors. The scientists then examined the fruit fly's 61 other odorant receptors and found that the proteins never made it to the ends of the olfactory neurons, called dendrites, where they would normally interact with the different incoming smells.
"The odors that interest flies in the outside world float around in the air until they contact tiny hairs on the fly's antennae," Vosshall says. "The odors pass through tiny holes in the hairs where they bind the odorant receptors at the ends of nerve cells. But in the mutant flies those odorant receptors fail to be delivered to the nerve endings, or dendrites. As a result, the flies are blind to smells.
Odorant receptor proteins, even within one species, are very different from one another. Researchers think that each of these receptors binds a different set of smell molecules, helping the insect recognize a large number of odors in the environment. When comparing the receptors across species there are groups of receptors that are only found in mosquitoes and then different groups specific to fruit flies. These differences most likely tailor each insect's sense of smell to its preferred plant or animal target. For fruit flies, these receptors may help the fly target rotting fruit, and in malaria mosquitoes, they are probably specific for human body odor. But Or83b is highly similar among insects, regardless of their particular smell preferences.
Vosshall and colleagues placed Or83b from the different species into mutant fruit flies that were missing their own Or83b gene to determine if the function of the protein was also conserved. They found that even though the genes were from very different species, these genes from other insects restored the fly's sense of smell.
Then they looked closer at the olfactory nerve cells. While in mutant flies the other odorant receptors were never transported to the dendrite, the receptors in flies making Or83b from the different species were all correctly located at the ends of the olfactory neurons.
Though it remains to be shown that the different Or83b genes are similarly essential for the sense of smell in each respective insect species, Vosshall is confident that this information may provide a starting point for future designs of pesticides and disease-controlling insect repellents.
"Although mosquitoes and flies have very different opinions about odors," Vosshall says, "this gene functionally substitutes. Insects are very smart and have evolved a lot, but from the point of view of vulnerability, this makes them very vulnerable to strategies that would block their sense of smell. If we could use this to chemically interrupt the transport of the odorant receptors, we could make mosquitoes 'blind' to humans. That in turn would be a good way to prevent disease transmission."
First author Walton D. Jones is a Biomedical Fellow in the Laboratory of Neurogenetics and Behavior at Rockefeller University. Contributing authors from Sentigen Biosciences include Thuy-Ai T. Nguyen, Brian Kloss and Kevin J. Lee.
This work was funded by grants to Vosshall from the NSF, the NIH, as well as the Beckman, McKnight and John Merck Foundations.
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