Researchers identify gene that helps fruit flies go to sleep

March 13, 2014, Johns Hopkins University School of 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 , 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 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 . 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.

The researchers found the same gene in every animal they studied: humans, mice, rabbits, chickens, even worms.

Importantly, when Wu's team looked to see where Wake was located in the mouse brain, they found that it was expressed in the suprachiasmatic nucleus (SCN), the master clock in mammals. Wu says the fact that the Wake protein was expressed in high concentrations in the SCN of mice is significant.

"Sometimes we discover things in flies that have no direct relevance in higher order animals," Wu says. "In this case, because we found the protein in a location where it likely plays a role in circadian rhythms and sleep, we are encouraged that this protein may do the same thing in mice and people."

The hope is that someday, by manipulating Wake, possibly with a medication, shift workers, military personnel and sleep-onset insomniacs could better.

"This novel pathway may be a place where we can intervene," Wu says.

Explore further: New fruitfly sleep gene promotes the need to sleep

Related Stories

New fruitfly sleep gene promotes the need to sleep

February 4, 2014
All creatures great and small, including fruitflies, need sleep. Researchers have surmised that sleep – in any species—is necessary for repairing proteins, consolidating memories, and removing wastes from cells. But, ...

Scientists wake up to causes of sleep disruption in Alzheimer's disease

February 26, 2014
Being awake at night and dozing during the day can be a distressing early symptom of Alzheimer's disease, but how the disease disrupts our biological clocks to cause these symptoms has remained elusive.

Researchers identify new circadian clock component

May 16, 2013
Northwestern University scientists have shown a gene involved in neurodegenerative disease also plays a critical role in the proper function of the circadian clock.

Scientists identify the switch that says it's time to sleep

February 19, 2014
The switch in the brain that sends us off to sleep has been identified by researchers at Oxford University's Centre for Neural Circuits and Behaviour in a study in fruit flies.

Neurotransmitter serotonin shown to link sleep–wake cycles with the body's natural 24-hour cycle

February 22, 2013
Almost all animals have a hard-wired 'body-clock' that controls biological function in cycles of approximately 24 hours. This is known as the circadian rhythm and, in mammals, it is controlled by signaling in a region of ...

Recommended for you

Research reveals atomic-level changes in ALS-linked protein

January 18, 2018
For the first time, researchers have described atom-by-atom changes in a family of proteins linked to amyotrophic lateral sclerosis (ALS), a group of brain disorders known as frontotemporal dementia and degenerative diseases ...

Fragile X finding shows normal neurons that interact poorly

January 18, 2018
Neurons in mice afflicted with the genetic defect that causes Fragile X syndrome (FXS) appear similar to those in healthy mice, but these neurons fail to interact normally, resulting in the long-known cognitive impairments, ...

How your brain remembers what you had for dinner last night

January 17, 2018
Confirming earlier computational models, researchers at University of California San Diego and UC San Diego School of Medicine, with colleagues in Arizona and Louisiana, report that episodic memories are encoded in the hippocampus ...

Recording a thought's fleeting trip through the brain

January 17, 2018
University of California, Berkeley neuroscientists have tracked the progress of a thought through the brain, showing clearly how the prefrontal cortex at the front of the brain coordinates activity to help us act in response ...

Midbrain 'start neurons' control whether we walk or run

January 17, 2018
Locomotion comprises the most fundamental movements we perform. It is a complex sequence from initiating the first step, to stopping when we reach our goal. At the same time, locomotion is executed at different speeds to ...

Neuroscientists suggest a model for how we gain volitional control of what we hold in our minds

January 16, 2018
Working memory is a sort of "mental sketchpad" that allows you to accomplish everyday tasks such as calling in your hungry family's takeout order and finding the bathroom you were just told "will be the third door on the ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.