Fooling Anopheles: Scientists Aim to Wipe Out Malaria by Outsmarting a Mosquito's Sense of Smell

October 21, 2002

Malaria is a devastating illness that kills 2.7 million people each year and threatens more than 40 percent of the world's population. But scientists supported by the National Institute on Deafness and Other Communication Disorders (NIDCD) are steps closer to foiling the pesky vector responsible for transmitting the disease, according to a new study published in the Oct. 4, 2002, issue of Science. The journal issue is dedicated to the genetic study of Anopheles gambiae, the species of mosquito that is responsible for the spread of most malaria cases in the world, particularly those occurring throughout Africa. Malaria is caused by a one-celled parasite that spends part of its life cycle inside mosquitoes, and the other part inside humans. The disease spreads when an uninfected mosquito bites an infected human, becomes infected, and subsequently bites an uninfected human.

"In every mosquito's life, there are fleeting windows of time when it must make an important decision: Who or what will I bite?" said Dr. Laurence Zwiebel, assistant professor of biology at Vanderbilt University, Nashville, Tenn. "And it makes this decision largely with its nose." Zwiebel and other researchers from Vanderbilt collaborated with scientists from the University of Notre Dame, Notre Dame, Ind., the University of Illinois at Urbana-Champaign, Ill., and Celera Diagnostics, Rockville, Md., on a study to better understand some of the molecular events that lie behind these decisions.

Zwiebel and his colleagues believe that if they can understand the mosquito's sense of smell and taste at the molecular level, where, for example, odor molecule meets the mosquito's readied odorant receptors, they can figure out how to thwart the process, preventing the mosquito from biting humans and transmitting the disease any further.

Using methods in bioinformatics, a field that employs computer technology to sort and make sense out of reams of biological data, from the genes composing a species' genome to the amino acid sequences that make up individual proteins, Zwiebel and the team of researchers identified 276 genes that code for all of the G protein-coupled receptors (GPCRs) in Anopheles. A GPCR is a type of protein that has a characteristic structure-looping in and out of a cell membrane seven times-and that helps the cell respond to substances in its environment. Of the 276 GPCRs, the majority (155) are devoted to the chemical senses alone: 79 for smell and 76 for taste.

The researchers compared chemosensory receptor proteins encoded by Anopheles's genes to those encoded by the genes of a cousin, Drosophila melanogaster, or the fruit fly. While some GPCRs were similar in both species, a large portion of GPCRs for taste and smell were unique to each species--more than one-third in the case of Anopheles's smell receptors. The researchers suggest that the unique receptors may be responsible for the detection of smells important to the different lifestyles of the two species: namely human scents in the case of Anopheles, and rotting fruit odors in the case of the fruit fly.

Furthermore, using molecular analysis, they found that the genes for the majority of smell receptors they identified are expressed only in the mosquito's chief olfactory organs--its antennae--thus supporting their results.

The findings may ultimately be useful in developing new repellants and attractants that are smarter, more economical, and more ecologically friendly, while helping to fight malaria and other mosquito-borne diseases, such as West Nile virus, dengue, and yellow fever. For example, Zwiebel noted, if the mosquito’s olfactory machinery were somehow compromised, a scent that is normally attractive to the mosquito could become repulsive, just as too much cologne or perfume can be repulsive to humans; conversely, an attractive odor could be used to lure a colony of mosquitoes to a large tank of hyper-concentrated insecticide.

The research also was supported by the United Nations Development Program/World Bank/World Health Organization Special Program for Research and Training in Tropical Diseases, Celera Diagnostics, and the Anopheles Gambia Genome Consortium.

As the nation's focal point for research in human communication, the NIDCD supports and conducts research and research training on normal mechanisms as well as diseases and disorders of hearing, balance, smell, taste, voice, speech, and language that affect millions of Americans.

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