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Meet Nemuri, the Gene That Puts Flies to Sleep and Helps Them Fight Infection

A team of researchers looked at 8,015 genes and found one that made the insects super-sleepers

Common fruit flies are ideal for complex genetic screens because of their short lifespan, relatively small genome and low cost. (iStock / rob_lan)
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A friend might recommend a good night’s rest when you’re feeling sick. This simple remedy is actually grounded in science—and a new study shows it might be embedded in DNA, at least in fruit flies.

There’s an established correlation between sleep and the immune system, but scientists have had difficulty defining the relationship. Now, a team of researchers have come one step closer to establishing a clear-cut connection; they found a single gene in fruit flies that boosts sleep when insects are sick or exhausted, according to a paper published today in Science.

The team—led by Amita Sehgal, a neuroscientist at the University of Pennsylvania—dubbed the gene nemuri, a Japanese word for sleep. While previous tests identified genes that reduce sleep when they're missing, this is the first fly study to identify a single gene that, when overactive, improves sleep. An abundance of nemuri also helped the flies fight infection, presenting a clear connection between this sleep gene and the immune system.

“This is quite an important breakthrough in the sense that it provides a mechanistic link between these two completely different things—sleep and immune response—that appear to be very linked,” said Grigorios Oikonomou, a neuroscientist who studies sleep genetics in zebrafish at California Institute of Technology, but was not involved in this experiment.

How many flies did it take to pinpoint this single gene, which could help us unravel the connection between sleep and immunity? By Sehgal’s estimate, almost one million. Thousands of groups of flies were engineered to turbo-express different genes by adding a drug to the insects’ typical diet of corn meal, molasses, yeast, and agar.

Flies, as it turns out, are sleepy creatures. In the lab, they doze around 11 hours a day. “Sleep” for flies is defined as five or more minutes of immobility, which can be measured by video tracking or checking whether their movement breaks an infrared beam within their test-tube home. The researchers monitored 8,015 different types of genetically-altered flies as they snoozed, but after a lengthy process of elimination, one single group dramatically out-slept the rest.

These outliers—the nemuri group—netted a whopping 17 to 20 hours of sleep per day.

“We were very surprised that we only got one [gene out of 8,000],” says Sehgal.

The researchers also tested “sleep depth,” or how readily flies woke up when startled by a plastic mallet being dropped onto the container they were housed in. The shock was enough to rouse over 94 percent of regular flies from their slumber. More than 80 percent of the nemuri-boosted flies, on the other hand, slept right through the racket.

Nemuri is good for more than inducing sound sleep: Flies with extra nemuri were better at fighting the flu. When infected with two kinds of deadly bacteria, the nemuri-boosted flies survived longer than their counterparts that expressed nemuri at normal levels.

It turns out nemuri also functions as an antimicrobial peptide (AMP), meaning that it’s quite effective at killing microbes on its own. Flies expressing the gene at typical levels had nearly undetectable traces of the AMP. What did trigger the normal flies' brains to pump out more nemuri was sleep deprivation—by being shaken roughly every 20 seconds—and sickness.

These results, Sehgal explained, indicate that “sleep regulation is closely linked to the immune system, in particular how the body deals with sleep deprivation.”

Finding a molecule that has evolved to induce sleep and also has a separate microbe-slaying function “is very suggestive that actually, sleeping is good for you when you’re sick,” says Oikonomou, who co-authored a perspective paper in Science that accompanies Sehgal’s study.

Having lots of nemuri clearly induced sleep, but the team also wanted to know whether the flies’ slumber would be affected if nemuri was eliminated completely. To test this, Sehgal’s team bred mutant flies lacking both copies of the nemuri gene, so they were completely unable to manufacture its antimicrobial benefits. The mutant, nemuri-lacking flies got the same amount of sleep as their normal, nemuri-possessing counterparts, although the study found that the mutants were more easily woken up by light flashes or a foreign smell and were slower to fall back asleep.

Flies with the nemuri gene did sleep longer after getting sick. But, Sehgal says, the mutants “do not die earlier than the controls, and we think that’s because there are other factors that compensate.”

In other words, the nemuri gene isn’t the end-all, be-all gene required for sleep or immunity. Without it, flies are still capable of sleeping, albeit more fitfully, and its absence doesn’t seem to impair them in resisting infection.

Chiara Cirelli, a neuroscientist at the University of Wisconsin-Madison who was not involved in the study, is interested in seeing what the nemuri gene’s effects are at less extreme levels.

“We knew there was this correlation, but here, we have an animal model, we have a specific gene, we can start asking these more mechanistic questions,” she says. The study opens up new avenues for research to drill down on the relationship between sleep and the immune system, explains Cirelli.

Sehgal would also like to know what other species, including humans, have nemuri or a gene like it. Further studying nemuri and its microbe-fighting protein could lead to “a much better sleep drug,” Oikonomou speculates, perhaps one with fewer side effects than what’s currently on the market.

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