50 Ways to Sniff a Human

In this corner, weighing in at 150 pounds: Homo sapiens, creator of the bug zapper, the citronella candle, the rolled-up newspaper and Deep Woods Off!

And in the opposite corner, weighing in at less than 5 milligrams: Anopheles gambiae, transmitter of 250 million new cases of malaria each year, possessing one—no, make that two—wicked sets of olfactory sensors. Or, quite possibly, several sets of olfactory sensors.

It now appears that the malaria mosquito uses more than one family of odor sensors to sniff out its human prey. That is the implication of new research into the mosquito’s sense of smell published in the Aug. 31 issue of the online, open-access journal Public Library of Science Biology.

Experiments described in the paper provide striking new evidence that Anopheles gambiae, which kills 900,000 people annually, has a second independent set of olfactory sensors that are fundamentally different from the set of sensors scientists have known about and have been studying for the past 10 years. The discovery may help explain a puzzling question that has been plaguing scientists trying to develop new and more effective forms of mosquito lures and repellents.


Chao Liu (left) and R. Jason Pitts

“The ORs [odorant receptors] that were identified in the lab earlier don’t respond to a lot of human odors,” says Vanderbilt graduate student Chao Liu, who is the lead author on the paper. “Now that we have a new set of receptors, we may be able to fill in the picture.”

There is a good chance that this new set of receptors may be specifically tuned to detect a number of the odorants given off by humans, adds co-author R. Jason Pitts, a senior research specialist and graduate student at Vanderbilt. “If this is the case, then it is quite likely this information will play a critical role in attempts to develop improved lures and repellents to control the spread of malaria.” According to Pitts, they also have preliminary evidence that the mosquito’s olfactory system may include additional families of sensors.

Vanderbilt Professor of Biological Sciences and Pharmacology Laurence Zwiebel, who was the principal investigator on the study, heads a major interdisciplinary research project to develop new ways to control the spread of malaria based on mosquito olfaction. The project is supported by the Grand Challenges in Global Health Initiative funded by the Foundation for NIH through a grant from the Bill & Melinda Gates Foundation.

“It’s not at all surprising that the mosquito’s olfactory system is more sophisticated than we thought,” says Zwiebel. “Olfaction is absolutely essential to the mosquito. If the female cannot find a host for a blood meal, she cannot reproduce. As a result, mosquitoes have developed an uncanny ability to detect odors. This is true of all species of mosquitoes, not just Anopheles. So it is highly likely that the mosquitoes that spread West Nile, dengue fever, yellow fever and encephalitis also have similar sets of odor sensors.”

About 10 years ago, when the mosquito genome was first sequenced, scientists at Vanderbilt and Yale identified the genes and structure of one set of Anopheles sensors, called odorant receptors (AgORs). At first they thought these receptors had the same basic design as sensors found in the nose of humans and other mammals. But recent studies have found that the mosquito receptors, along with those of several other insects, have a distinctly different structure.

Last year when scientists at Rockefeller University announced they had discovered a second set of olfactory receptors in the fruit fly Drosophila melanogaster, an animal model for basic genetics, “it was like a light had switched on,” says Pitts. Vanderbilt researchers knew it was likely that the mosquito had a second set of receptors, too, and began searching for them.

The search was successful, and the researchers identified genes that code for about 50 versions of the new type of receptor. The new receptors appear to have a slightly different structure from that of AgORs: They are called “ionotropic receptors” (AgIRs), and they closely resemble the type of receptor found in the brain that responds to the common neurotransmitter glutamate.