May 30, 2013
Genetically Modified Mosquitoes Lose Their Sense Of Smell
April Flowers for redOrbit.com - Your Universe Online
Researchers at the Howard Hughes Medical Institute (HHMI) have altered the way insects respond to odors, including the smell of humans and the insect repellant DEET, in one of the first successful attempts at genetically engineering mosquitoes.
The findings, published in an issue of Nature, demonstrates that mosquitoes can be genetically manipulated using the latest research techniques. The results also pave the way to understanding why mosquitoes are so attracted to humans, and how to block that attraction.
"The time has come now to do genetics in these important disease-vector insects. I think our new work is a great example that you can do it," says Leslie Vosshall, an HHMI investigator at Rockefeller University.
Researchers announced the completion of the full genome sequence of Aedes aegypti, the mosquito that transmits dengue and yellow fever, in 2007. In 2008, when Vosshall joined HHMI as an investigator, she shifted her laboratory´s focus from Drosophila flies to mosquitoes. The laboratory´s new goal was to genetically engineer the insects, as Vosshall was fascinated with their importance as disease carriers and their unique attraction to humans. The team´s first target was a gene called orco, which her lab had deleted in genetically engineered flies 10 years earlier.
"We knew this gene was important for flies to be able to respond to the odors they respond to," says Vosshall. "And we had some hints that mosquitoes interact with smells in their environment, so it was a good bet that something would interact with orco in mosquitoes."
To specifically mutate the orco gene in Aedes aegypti, the team turned to a genetic engineering tool called zinc-finger nucleases, which were injected into mosquito embryos. The team then waited for them to mature, identified mutant individuals, and generated mutant strains that would allow them to study the role of orco in mosquito biology. Those strains showed diminished activity in neurons linked to odor-sensing. Further changes were revealed with behavioral testing.
Normal Aedes aegypti, when given a choice between a human and any other animal, will reliably buzz toward the human. The strains with orco mutations, however, showed reduced preference for the smell of humans over guinea pigs, even in the presence of carbon dioxide, thought to help the mosquitoes respond to human scent. "By disrupting a single gene, we can fundamentally confuse the mosquito from its task of seeking humans," says Vosshall.
The scientists are still unsure whether the confusion stems from an inability to sense a “good” smell coming from the human, a “bad” smell coming from the guinea pig, or both.
The team also tested whether mosquitoes with the mutated orco gene responded differently to DEET.
The mosquitoes were presented with two human arms — one slathered in a solution containing 10 percent DEET, the active ingredient in many bug repellants, and the other untreated. The mosquitoes swarmed both arms equally, suggesting they couldn´t smell the DEET. However, once they landed on the DEET-covered arm, they quickly flew away.
"This tells us that there are two totally different mechanisms that mosquitoes are using to sense DEET," explains Vosshall. "One is what's happening in the air, and the other only comes into action when the mosquito is touching the skin." Scientists have suggested before that such a dual mechanism existed, but it had never been shown.
Future investigations for Vosshall and her team will include a more detailed study of how the orco proteins interact with the mosquitoes odorant receptors to allow the insects to sense smells.
"We want to know what it is about these mosquitoes that makes them so specialized for humans," she says. "And if we can also provide insights into how existing repellants are working, then we can start having some ideas about what a next-generation repellant would look like."