Mosquito nose transplanted to frogs, flies

To combat malaria, we must understand the mosquito’s nose

Malaria affects several hundred million people worldwide every year, and each year, more than one million people–mostly children–die of the disease. ┬áThe vectors for transferring the plasmodium that causes malaria to humans are female mosquitoes from the Anopheles genus. To combat these mosquitoes and this deadly disease, we must first understand the mosquito nose.

The mosquito sense of smell is localized to the animal’s antennae. There, nerve cells sense various odors (all smells are particulate!) via molecules of protein called receptors (because they “receive” the input). Scientists have reasoned that if they can understand which odors trigger these receptors–and thus, the mosquito’s interest–they may be able to develop odorants (smells) that distract the mosquito from people, thus reducing transmission of malaria.

Fruit flies and frogs with mosquito noses

While using the actual animal might seem to be the way to go, scientists turn to more standard laboratory models for such work. Fruit flies and frog eggs are long-time, well-characterized standbys in the lab environment, and specific manipulations allow researchers to introduce genes from other organisms into these species. Because fruit flies and frogs are such prolific animals, reproducing by the hundreds, the proteins that these introduced genes encode can be produced in the context of the whole organism in large numbers. In science and industry, a process that allows big production outputs like this is called “high throughput.”

The labs of Dr. John Carlson of Yale and Dr. Lawrence Zweibel of Vanderbilt have respectively co-opted the fruit fly (Drosophila melanogaster) and a frog (species not specified) as their method of high-throughput production of these mosquito nose proteins. The fly approach is a bit slower, involving painstaking insertion of the mosquito genes into flies one at a time. The flies express the proteins in their own antennae, a replacement for their own receptors that have been knocked out.

The frog egg approach is more truly high throughput, as the engineered frog eggs express an abundance of the mosquito nose proteins. The smell-sensitive egg then can be tested using a system that measures nerve signals: Whenever a specific odorant dissolved in the buffer solution surrounding the egg sets off the nose protein receptor, the system registers the electrical response.

The flies are good for testing compounds that volatilize in air, showing by their behavior whether or not the odor attracts, while the frog eggs allow for a more truly high-throughput analysis. Together, they make quite a team when it comes to testing the mosquito’s sense of smell.

Frogs and flies, working together

The two labs tested each system using 72 receptors from the Anopheles “nose” and a panel of 110 odorants. The mosquito-nosed frog eggs and mosquito-nosed flies yielded results that pretty much matched: Some receptors are generalist types, reacting to just about any smell, but a special few focus more on specific odors. As it turns out, 27 of these receptors are fine-tuned to respond to the odorants in human sweat. The results from these studies are reported simultaneously in two papers, one in Nature and one soon to appear in the Proceedings of the National Academy of Sciences.

A decoy smell for the mosquito

Why go to all the trouble to make mosquito noses in flies and frogs? The hope is to use these high-throughput methods to identify compounds that can serve as decoys for the mosquitoes by deceiving these “nose” receptors. If researchers can identify an eau d’ sweat that distracts the mosquito away from a human target or an odorant combination that repels the mosquito from people, the outcome could be a decrease in transmission rates of malaria.

UPDATE: Malaria does not distinguish between kings and commoners: News reports indicate that the microscopic plasmodium may have felled King Tut himself.

Ideas for questions

Why do scientists focus on species like fruit flies or frogs (e.g, Xenopus laevis) when they do research like this? Why not use the species being studies instead?

Do some research on the relationship between the malarial plasmodium and the mosquito. Do all species of mosquito transmit this pathogen? What distinguishes species that transmit malaria?

The article references measuring electrical activity in the frog eggs in response to odorants. Look up “voltage clamp.” How is that used to measure electrical activity?

World/public health question: What has been done in the past to combat malaria? How effective were these efforts? What is being done today? Some efforts are high-tech, like the studies described above. Some are low-tech. Can you identify a few examples of each?

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