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Novel gene links sleep and immune system

NEMURI, a newly characterized gene, promotes sleep and fights microbes

by Alla Katsnelson, special to C&EN
January 31, 2019

Image showing the protein nemuri expressed in green the brains of flies that have been infected with bacteria.
Credit: ACS Central Science
Sleeping it off: NEMURI expression (green) is especially high in the brains of flies infected with bacteria.

Think back to your last bad cold or nasty stomach bug. Chances are you felt not only rotten, but also remarkably sleepy. Now, researchers have identified a gene in Drosophila that provides a biological link between these two effects (Science 2018, DOI: 10.1126/science.aat1650). The gene — dubbed NEMURI, which means “sleep” in Japanese — has a dual job: the secreted peptide it encodes has antimicrobial properties and also helps flies sleep.

“We’ve always known that you sleep more when you’re sick and that sleep helps with recovery, but it wasn’t really known whether the mechanisms that turn on sleep when you’re sick are shared with the mechanisms that turn on sleep when you’re awake for a long time,” says Amita Sehgal, a molecular biologist at the University of Pennsylvania, who led the work. The results published today support the idea that they are, she says.

In the search for sleep-promoting genes, they overexpressed 8,000 candidates in adult flies. Only NEMURI fit the bill. Boosting its expression made the flies sleep longer and more deeply. Knocking it out didn’t make them sleep less, but made them easier to wake.

NEMURI had not been characterized before, but the protein’s molecular structure is similar to that of some anti-microbial peptides. So the researchers tested whether NEMURI had bacteria-fighting powers, too. They found that it did indeed kill bacterial cells grown in a dish, and that overexpressing it improved the flies’ survival and increased how much they slept during a bacterial infection. What’s more, NEMURI expression increased when the flies were deprived of sleep and when they were infected with bacteria.

Sleep researchers have long tried to distinguish the effects of sleep loss from the effects of the stress that often accompanies it. This study identifies a common molecular mechanism between these effects and suggests that the two are too intertwined to distinguish. “Sleep deprivation is inherently stressful, and it’s invoking the same pathways that are involved in stress and immune response,” Sehgal says.

The researchers are now investigating how exactly the peptide boosts sleep. They are also exploring whether this mechanism is conserved in mammals.

It’s challenging to prove that sleeping when you’re sick makes you get better faster — in other words, that one of the purposes of sleep is to improve immunity, says Grigorios Oikonomu, a postdoctoral researcher in the lab of David Prober, a sleep researcher at the California Institute of Technology. Indeed, this study doesn’t prove it, because knocking out NEMURI doesn’t lead to sleep loss. But it “provides some interesting support” for a possible link between sleep and immunity, he says.

Oikonomu notes that NEMURI is just one of 100 or so similar anti-microbial peptides. “It will be interesting whether any of those peptides also regulate sleep,” he says. If so, they might do a better job of treating insomnia than current sleep medicines.


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