The smell receptor that mosquitoes use to zero in on victims is likely present in other insects, according to Leslie Voshall.

To Leslie B. Vosshall, the two minutes a mosquito spends feeding on human blood are full of suspense: a mini-drama in which the insect, in need of extra protein or iron for egg-laying, risks her own life for the sake of her children. Each turning point in the story—the decision to seek blood, the identification of a victim, the escape from the inevitable swat—ignites Vosshall's deep curiosity about animal behavior.

Vosshall, who became an HHMI investigator in 2008, recently added mosquitoes to her Rockefeller University lab (which has focused primarily on fruit flies) because she wants to help block their ability to transmit infectious disease. Schemes to eradicate the pest do not interest her. Instead, she says, “We want to figure out the blood lust.”

“Most of what interests a mosquito about you is how you smell,” Vosshall says. “If we can understand that and find a way to interrupt it, then we should be able to solve some problems in infectious disease transmission.”

Her team is still equipping the lab for mosquito research—constructing a screened-in zone outside a research room to capture escapees, for example—but Vosshall is well prepared scientifically to find out how and why mosquitoes seek their targets. Her career has focused on elucidating the molecular biology of insect olfaction.

As a postdoctoral fellow in 1993, Vosshall joined HHMI investigator Richard Axel's lab at Columbia University, when little was known about how insects receive and decode olfactory information. Working with fruit flies, she found the first major clue: a large family of genes that encode receptor proteins embedded in the membranes of olfactory neurons. Later, from her own lab at Rockefeller, she mapped how the neurons that express these proteins project into the brain, creating an invaluable tool for correlating odorant receptors to the odor molecules that activate them.

Many of Vosshall's more recent discoveries on insect olfaction have surprised others in her field. “The way insects smell odors is very strange,” she says. “Their odorant receptors don't look like any other protein on earth.” She showed in 2008 that, unlike mammalian olfactory receptors, which activate signaling pathways inside the cell, insect odorant receptors function as channels that open to let ions flow into the cell when an odor molecule binds. Also unusual, she found, is the existence of an olfactory co-receptor that is present in nearly all insect olfactory neurons and that works in tandem with odorant receptors for specific smells.

That co-receptor, OR83b, is a potential target for what Vosshall describes as an “olfactory confusant,” noting that “a protein like OR83b exists in every insect on earth. If we find a chemical that jams this receptor and prevents it from working, we should be able to block the sense of smell in every insect.” A fast-acting molecule that blocks OR83b could be sprayed indoors or worn on the body to keep bugs away.

In fact, her lab showed last year that the common insect repellent DEET works in part by inhibiting OR83b. “It works pretty well, but it's not acting as a universal inhibitor,” she says. Her lab is screening chemicals for a more effective alternative.

Photo: Peter Ross

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