Researchers in the Walter Leal lab, UC Davis Department of Entomology, are engaging in some exciting research.

They just discovered a "generic insect repellent detector" in the fruit fly (Drosophila melanogaster)--research published today (March 16) in PloS One (Public Library of Science).

What's exciting is that this research may lead to more effective and lower-cost products than DEET, the gold standard of insect repellents.

The five-member team found the sensory organs involved when fruit flies detect and avoid three key insect repellents: DEET, IR3535 and picaridin.  They identified the olfactory receptor neuron (ORN) and characterized its receptor, DmOr42a.

The research team of Leal; primary author and chemical ecologist Zain Syed; chemical ecologist Julien Pelletier; and undergraduate students Eric Flounders and Rodrigo Chitolina, first found that the fruit fly avoids all three well-known repellents, DEET, IR3535 (a compound known as Avon Corporation’s “Skin-So-Soft Bug Guard”) and picaridin (derived from pepper) and then set out to find olfactory  receptor neurons sensitive to those insect repellents. They scanned all olfactory sensilla in the antennae and the mouthpart structure, maxillary palps, using single unit electrophysiological recordings.

The receptor they found “fulfills the requirements for a simplified bioassay for early screening of test insect repellents,” they wrote in the scientific paper.

When you think that it takes about 10 years and $30 million to develop a new repellent--and only one test compound in 20,000 reaches the market--this could really speed up the process.

Zain Syed told us: "In this study, by using established behavioral assays to dissect the mechanism of repulsion in fruit flies, we demonstrated for the first time that Drosophila equally avoid other repellents--picaridin and IR3535. By challenging every type of olfactory sensilla on the antenna and maxillary palps, we identified neurons and then the odorant receptor that detect these repellents."

The UC Davis research, as Syed said, "adds a new dimension in research towards understanding the molecular, cellular and organismal response to repellents."

Chemical ecologist Coby Schal, the Blanton J. Whitmire Distinguished Professor of Entomology at North Carolina State University, praised the research as “an excellent example of translational research that can lead to a streamlined and less expensive path of discovery of new repellents.”

In earlier research, Syed and Leal identified a DEET-sensitive olfactory receptor neuron in the Southern House mosquito. “Going from the neuron to the receptor, however, is like looking for the proverbial needle in a haystack as the mosquito genome has some 181 olfactory receptor genes,” Schal said.

The Leal lab knows DEET. Back in August 2008, Leal and Syed drew international attention when they announced they'd discovered DEET’s mode of action or how it works.  Scientists long surmised that DEET masks the smell of the host, or jams or corrupts the insect’s senses, interfering with its ability to locate a host. The Leal-Syed research showed that mosquitoes actually smell DEET and avoid it because they dislike the smell.

DEET, developed by scientists at the U.S. Department of Agriculture and patented by the U.S. Army in 1946, is the go-to insect repellent. Worldwide, more than 200 million use DEET to ward off vectorborne diseases.

The female silkworm moth releases a sex pheromone, bombykol, that's very enticing to the male. He can detect it from miles away.

Now researchers in the UC Davis Department of Entomology have discovered that the fruit fly has a native odorant receptor that detects the silkworm moth’s sex pheromone, and that it’s “amazingly more sensitive” than the moth’s odorant receptor.

Their work could open research doors for insect-inspired biosensors.

Walter Leal, professor of entomology, and postdoctoral scholar Zain Syed know the olfactory systems of silkworm moths (Bombyx mori) and fruit flies (Drosophilia melanogaster) well.

Their research follows on the heels of another study they published in PNAS in 2006 with the Deborah Kimbrell genetics lab in the UC Davis College of Biological Sciences. Bottom line: they  found that genetically engineered fruit flies responded to the silkworm moth scent of a female.

Now Leal and Syed have identified the odorant receptor in the male fruit fly that detects the sex pheromone.

Chemical ecologist Walter Leal, professor and former chair of the UC Davis Department of Entomology, and his postdoctoral researcher Zain Syed have done it again.

In August of 2008, they discovered the secret mode of the insect repellent, DEET. In groundbreaking research published in the Proceedings of the National Academy of Sciences (PNAS), they found that DEET doesn't mask the smell of the host (that would be you and me), nor does DEET jam the insect's senses.

Mosquitoes CAN indeed smell DEET. They avoid it because they don't like the odor.

Then on Monday, Leal and Syed published more groundbreaking research, also in PNAS. They identified the dominant compound that attracts Culex mosquitoes to both birds and humans.

It's a compound called nonanal, naturally produced in birds and humans. This not only explains the host shift from birds to humans, but paves the way for key developments in mosquito and disease control. 

Infected Culex mosquitoes transmit life-threatening diseases, including West Nile virus. Since 1999, the Centers for Disease Control and Prevention has recorded 29,397 human cases and 1,147 fatalities in the United States alone.

“Nonanal is how they find us,” Leal said. “The antennae of the Culex quinquefasciatus are highly developed to detect even extremely low concentrations of nonanal.” 

Researchers from throughout the country this week praised their work.  

Yale University professor John Carlson, a leading scientist in insect olfaction, described the study as “exciting with important implications for the intriguing question of how mosquitoes find the humans they bite.”

 “Leal and Syed have identified a human odor that is detected with great sensitivity by the antennae of mosquitoes that transmit West Nile virus,” Carlson said. “In addition to its scientific interest, the study may have important practical applications in the control of these mosquitoes and the diseases they carry.” 

Chemical ecologist Coby Schal, a professor at North Carolina State University, described the research as representing “some of the best research on insect olfaction that I have ever read. By combining trapping experiments in the field with careful characterization of the response profiles of antennal and maxillary sensilla of Culex mosquitoes, Syed and Leal show not only that the combination of carbon dioxide and nonanal is an important beacon for blood-seeking mosquitoes, but also that a large fraction of the sensilla on the mosquito’s nose (antennae) is dedicated to the detection of nonanal at incredibly low concentration.

“Such high sensitivity of olfactory receptor neurons to nonanal – rivaling the response characteristics of pheromone responsive neurons – suggests that nonanal has played an important role in the evolution of host-finding and host-preferences in Culex mosquitoes,” Schal said. “This is a truly exceptional achievement by the outstanding Syed/Leal team, but in step with their previous outstanding contributions on a wide range of arthropods.”

More information on the Leal lab research is on the Department of Entomology Web page. 

Leal, a newly elected Fellow of the Entomological Society of America (he's one of 10 entomologists to be so honored this year) and Syed, named one of the top post-doctoral researchers at UC Davis this year, have indeed done it again.

When you think of all the havoc that mosquito-borne diseases have wreaked, this is the kind of research that definitely deserves a round of applause. 

Dr. Leal and Dr. Syed are a highly efficient and effective SWAT team.

Chemical ecologist Zain Syed of the Walter Leal lab, University of California, Davis, knows just where to find mosquitoes for his research.

Rice fields.

He's been collecting up to 3000 mosquitoes a night along the Yolo Causeway, located on Interstate 80 between Davis and West Sacramento. The Yolo basin is home to the Vic Fazio Yolo Wildlife Area.

Syed is using carbon-dioxide traps to capture host-seeking mosquitoes. The female skeeters are seeking a blood meal (you, if you're around there). His traps entice them to "come on in."

"Once mosquitoes are lured to the vicinity," Syed says, "a suction fan traps them and sends them to the sleeve, a mesh bag that holds mosquitoes."

The mesh bag below holds 2000 mosquitoes. They are mostly Culex tarsalis, but also some Culex pipiens.

Culex mosquitoes are known for transmitting West Nile virus.

Syed and Leal are known for uncovering the mode of action for DEET, the chemical insect repellent used by more than 200 million people worldwide. Their groundbreaking research last year found that DEET doesn't jam a mosquito's senses or mask the smell of the host, as scientists previously thought for some 50 years. Mosquitoes avoid DEET because it smells bad to them.

Syed recently won one of two coveted campuswide awards for excellence in postdoctoral research from a field of 800 postdocs.

But other fields--rice fields--have always drawn his attention.

That's where the skeeters are.