For more than a century, biologists have been studying sleep. And over the decades, interesting findings have piled up: Sleep deprivation, we now know, can be lethal. Sleep pressure — the need for sleep — increases the longer you’re awake. In humans and other mammals, sleep is very recognizable in readings of brain activity. Early on, the squiggling line of an EEG readout starts to form kinks called sleep spindles, unfurling across the glowing screens inside sleep labs.

But for all these meticulous observations, the molecular machinery behind our nightly departure from consciousness remains one of the deepest mysteries in modern biology. “On a mechanistic level,” said Amita Sehgal, a chronobiologist at the University of Pennsylvania who has pioneered the study of sleep using fruit flies, “we don’t know what’s happening to make us sleepy.” Biologists have mutated thousands of lab organisms like flies, picked out those with sleep abnormalities, and studied their genes, as well as those of people with sleep disorders. The idea is that if we can identify which genes are disrupted — what is making people fall asleep at their desks, or what makes flies too snoozy to mate — we’ll be closer to understanding why we get sleepy and what, on the molecular level, sleep consists of.

Now, a team of researchers in Japan and Texas have unveiled the first results of a colossal experiment that takes this approach with mice, on a scale never seen before: Over the course of several years, the team mutated the genes of thousands of mice, hooked them up to brain wave monitors and watched them sleep. In a recent paper in Nature, the researchers revealed two genes that seem to be involved in sleep’s biological machinery. The first was found in mice that need much more sleep than normal. The other comes from mice that spend less time in dreaming, or REM, sleep. The results suggest new leads for sleep researchers to chase, and they contribute to a rising tide of research dissecting the molecular underpinnings of sleep.

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