In the lottery of noses, humans well and truly missed out. But we've been able to harness the power of animals with better olfactory systems than ours, such as dogs, honey bees and locusts, to sniff out solutions to security and health problems. Now, scientists have created "super-sniffer" mice that are able to detect specific odors with increased precision, opening the door for new sensors for explosives and diseases – as well as a better understanding of our own olfactory system.
"This is one of our five basic senses, yet we have almost no clue how odors are coded by the brain," says Professor Paul Feinstein of Hunter College at City University of New York. "It's still a black box."
Mammals detect smells through a series of sensory neurons and receptors in the nose. Receptors are tuned to specific odors, and the attached neurons transmit the signal to the brain for processing. You'll find a fairly even distribution of different receptors in any given mammalian nose, but we don't quite know how our DNA tells the neurons which receptors to "choose" as our olfactory system develops.
In an attempt to better understand the mysteries of our noses, the researchers experimented with the mouse genome, injecting DNA containing a specific odor receptor into a fertilized egg cell, along with extra DNA strings to alter the probability of the gene being chosen. After a few attempts, the result was a series of mice with olfactory systems that contained more receptors tuned to detect the smell of the compound acetophenone, along with a fairly even distribution of other receptors.
The team tested for this by exposing the mice to that specific odor, and using fluorescent imaging found that the desired receptor was present in larger amounts than usual. In practice, the mice were trained to avoid an odor that binds to those receptors. When presented with that odor in water, the engineered mice were able to detect it at levels two orders of magnitude fainter than control mice.
"The animals could smell the odor better because of the increased presence of the receptor," says Charlotte D'Hulst, another of the team's researchers.
In order to study human olfaction, D'Hulst had experimented with gene swapping to replace the receptor gene of a mouse with one from a human. But it hadn't been working, until she tried Feinstein's transgenic method.
"We have developed a system where we can study human odor receptors and finally determine how human odor coding works," says Feinstein.
"Without understanding how odors bind to receptors, people have no rational way of designing new odors," says D'Hulst. "They also have no way of boosting the diminished smell capacity in patients with diseases such as Parkinson's."
Potential applications for the super-sniffing mice include training them to detect explosives, and diagnosing disease. The team is currently commercializing the technology through a company called MouSensor.
The research was published in the journal Cell Reports.
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