"Once we show that the mosquito receptors function in the same way as the fly receptors, we take a hint from drug companies--once they have a protein target in mind, [we] can screen for inhibitors of it." says neurogeneticist Leslie Vosshall, the lead author on the study, published in this week's issue of Nature.
It has been known since 2001 that when neurons in the fruit fly's antennae sense carbon dioxide, they release the chemosensory receptor protein Gr21a. Based on her research, and that of others, however, Vosshall knew that insects need two receptor proteins to detect common smells like fruits and flowers. "One of them binds to the smell," she says, "and the other one is critically important to make the [binded protein] function."
By examining other taste receptors in the fly's antennae, Vosshall's team discovered that one particular protein--Gr63a--is coexpressed with Gr21a in both larvae and adults. By genetically engineering flies that only released one of the two proteins, the Rockefeller group determined that a combination of the two is necessary to get the antennae neurons buzzing. For instance, a strain of fly with a mutated version of Gr63a could not detect concentrated carbon dioxide mixtures that normal flies--which are carbon dioxide-averse--would flee from.
Vosshall then turned to the mosquito genome to search for genes akin to those of flies. The team found two strong candidates: GPRGR22 and GPRGR24. "They are 62 percent and 48 percent identical, which, in the world of chemosensory receptors, is very similar," Vosshall notes. "There's very little in common between the fruit fly and the mosquito as regards other taste receptors and smell receptors, so these are pretty strongly conserved."
Unlike the flies, however, mosquitoes have their carbon dioxide-sensing neurons in their maxillary palps (specialized sensory organs located on either side of the insect's proboscis, which the female uses to draw blood from her host). Greg Suh, a researcher at the California Institute of Technology whose lab first identified the fruit fly's carbon dioxide-sensitive neurons, believes the locations of the neurons may explain a major behavioral difference between the insect species: "That's maybe the reason why," he speculates, "mosquitoes are attracted to CO2 whereas fruit flies are repelled by it."
Vosshall now wants to disable these receptors--at least in the case of mosquitoes--by developing an effective repellant. The current industry-standard compound in bug spray is DEET but, according to Vosshall, no one knows exactly how it works. She believes that her lab will be able to improve on DEET by inhibiting GPRGR22 and GPRGR24. "Whatever we devise would need to be safe, cheap & so that it can be used in the developing world," Vosshall says. "They would have to be the kinds of molecules that would sit safely on your skin, but also form a cloud around you and act on the mosquitoes that are about to bite you."