'Perfume' to lure mosquitoes and control malaria

06/30/05



Fruit flies are key to deciphering mosquito "smell"receptors
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New Haven, Conn. -- A five-year, $8.5-million dollar research project, designed to substantially reduce the spread of malaria by redirecting mosquitoes with odor cues, is being undertaken by an international team of scientists including John Carlson, the Eugene Higgins Professor of Molecular, Cellular, and Developmental Biology at Yale University.

The project is one of the 43 "groundbreaking" research projects to improve health in developing countries that have been offered a total of $436 million in support from a Grant from the Foundation for the National Institutes of Health through the Grand Challenges in Global Health initiative. Carlson, will work on a project with scientists at Vanderbilt University, which will administer the award, Wageningen University in the Netherlands, Ifakara Health Research and Development Centre in Tanzania and the Medical Research Council Laboratories in Gambia (Africa).

Hundreds of millions of people are infected with malaria -- and hundreds of thousands die -- annually. Female malaria mosquitoes "smell" with specialized receptors in their antennae and are drawn to particular human odors that say "dinner." After biting, while the mosquito feeds on blood that is needed for its egg production, parasites from the mosquito enter and infect the human. When an infected person is bitten again, the parasite can be transmitted to an uninfected mosquito and spread further.

The specific aim of the project is to reduce the population of malaria transmitting mosquitoes by identifying effective "perfumes" that act as attractants to traps or as mosquito repellents. Scientists at Yale and Vanderbilt will identify odors that act on mosquito receptors and create the "perfumes," and the Dutch researchers will study the mosquito behaviours that the odors elicit. Odorant blends giving the strongest reaction (attracting, repelling or causing confusion) will then be tested in a simulated natural situation in Ifakara, Tanzania. And finally, the ideal blend of odors will be sent to African villages in Gambia and Tanzania for full-scale, practical tests in different geographical extremes and mosquito populations.

The eventual products will keep malarial mosquitoes from infecting humans and will be inexpensive, safe for humans, livestock and crops, and easy to use in rural locations. It is hoped that they may also be used against other pathogenic mosquitoes, such as Aedes aegypti, which spreads dengue fever , and Culex pipiens, carrier of the West-Nile virus.

The search for compounds affecting mosquito olfaction will initially be carried out in a system, developed in Carlson's laboratory, in which the mosquito receptors are made in the antenna of genetically engineered fruit flies, Drosophila, that can be studied much more easily than the mosquito itself. In research published last year in Nature, Carlson and graduate student Elissa Hallem used the system to show that one particular mosquito odor receptor responds strongly to a component of human sweat. Such receptors will now be tested with a large collection of other compounds to identify molecules useful as attractants or repellents.

The project is based largely on earlier work carried out by the Carlson laboratory that identified the first insect odor receptors, using a novel computer algorithm, as well as the first insect taste receptors. Last year, in a study published in the journal Cell, Hallem and Carlson established a comprehensive receptor-to-neuron map of the fly's antenna.

In two studies published earlier this year in Neuron, the laboratory reported major work on the mechanism of olfaction. The first showed that two functional odor receptors can be co-expressed in one neuron, a breach of one of the most central tenets in the field of olfaction. The second identified the molecular basis of odor coding in the insect's larval stage. Much of the research was done by graduate students in Carlson's laboratory, five of whom have won awards for their Ph.D. theses in the past six years.

Carlson, a Harvard University graduate and Stanford University Ph.D., joined the Yale faculty in 1986. He received Yale's Dylan Hixon Award for Excellence in Teaching in the Natural Sciences in 1998, a McKnight Investigator Award in 2000, and in 2004 he won the Silverstein-Simeone Award from the International Society of Chemical Ecology and a Senior Scholar Award from the Ellison Medical Foundation.

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