Researchers identify gene that helps fruit flies go to sleep

PUBLIC RELEASE DATE:

13-Mar-2014

Contact: Stephanie Desmon sdesmon1@jhmi.edu 410-955-8665 Johns Hopkins Medicine

In a series of experiments sparked by fruit flies that couldn't sleep, Johns Hopkins researchers say they have identified a mutant gene dubbed "Wide Awake" that sabotages how the biological clock sets the timing for sleep. The finding also led them to the protein made by a normal copy of the gene that promotes sleep early in the night and properly regulates sleep cycles.

Because genes and the proteins they code for are often highly conserved across species, the researchers suspect their discoveries boosted by preliminary studies in mice could lead to new treatments for people whose insomnia or off-hours work schedules keep them awake long after their heads hit the pillow.

"We know that the timing of sleep is regulated by the body's internal biological clock, but just how this occurs has been a mystery," says study leader Mark N. Wu, M.D., Ph.D., an assistant professor of neurology, medicine, genetic medicine and neuroscience at the Johns Hopkins University School of Medicine. "We have now found the first protein ever identified that translates timing information from the body's circadian clock and uses it to regulate sleep."

A report on the work appears online March 13 in the journal Neuron.

In their hunt for the molecular roots of sleep regulation, Wu and his colleagues studied thousands of fruit fly colonies, each with a different set of genetic mutations, and analyzed their sleep patterns. They found that one group of flies, with a mutation in the gene they would later call Wide Awake (or Wake for short), had trouble falling asleep at night, a malady that looked a lot like sleep-onset insomnia in humans. The investigators say Wake appears to be the messenger from the circadian clock to the brain, telling it that it's time to shut down and sleep.

After isolating the gene, Wu's team determined that when working properly, Wake helps shut down clock neurons of the brain that control arousal by making them more responsive to signals from the inhibitory neurotransmitter called GABA. Wake does this specifically in the early evening, thus promoting sleep at the right time. Levels of Wake cycle during the day, peaking near dusk in good sleepers.

Flies with a mutated Wake gene that couldn't get to sleep were not getting enough GABA signal to quiet their arousal circuits at night, keeping the flies agitated.

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Researchers identify gene that helps fruit flies go to sleep