Any jet-lagged tourist, shift worker or sleep-deprived student knows first-hand the miseries that a wonky biological clock can wreak - on our alertness, our wakefulness, our appetites and even our libidos.
But what has not been so well understood by scientists is how the brain's timekeeper neurons use electricity to regulate our bodies' 24-hour physiological rhythms.
Now, a joint NYU Abu Dhabi and New York study examining mutant fruit flies has found a previously unknown component of the molecular circuitry that sets our sleep-wake cycles and other natural responses.
Knowing how to manipulate the amount of electrical activity zapping within cells could eventually lead to the development of treatments to remedy sleep disorders, said Dr Kris Gunsalus, a professor with NYU Abu Dhabi and co-author of the study.
She calls the finding "a new link in a chain" of biological oscillations.
"When you're jet-lagged, your cells are adjusted to a different time zone. They might be in an 'evening state' in the morning, or a 'morning state' in the evening," she said. "But if you could take a pill at nighttime that makes your cells behave like they're in the evening state, then maybe it can help reset your clocks better."
Circadian rhythms, our internal alarm clocks, are mechanisms driven by neurons in our brains, which regulate cyclical diurnal (active in the morning) and nocturnal (active at night) behaviours. "When light comes on, we wake up, we're active in the day," Dr Gunsalus said. "Then in the evening, we start to make chemicals that make us sleepy, and then we go to sleep and rest during the night."
Humans can be sensitive to meddling with these circadian patterns. For example, many North Americans and Europeans affected by the semi-annual time change would have felt better rested upon waking up the next morning, owing to the winding back of clocks by one hour. An extra hour of slumber can go a long way.
Although it has long been known that external stimuli such as light-dark cycles can reset our clocks, what the NYU team found was that an internal mechanism also has a role in regulating the physiological processes.
Dr Gunsalus, who works at NYU Abu Dhabi's Centre for Genomics and Systems Biology, and colleagues at NYU New York, found that the expression of the genes that govern that behaviour are responsive to the amount of electrical activity within "pacemaker" neurons in the brain.
Dr Justin Blau, the leading NYU researcher on the study, refers to that mechanism as a zeitgeber, German for time giver, and says the finding "shifts the emphasis away from clock genes" towards "how clock neurons function in a neural network to regulate behaviour".
During their investigation of mutated drosophilia fruit flies - simple organisms that are easily bred in labs and have "clock genes" similar to humans - Dr Gunsalus and her New York City-based colleagues came across evidence that circadian rhythms function more like closed electronic circuits than previously thought.
"There are some cues that can train the clock, things like light and dark," she said, adding that "the clock sends out electrical signals that dictate behaviour" such as sleep, thirst and body temperature.
"But we found that in addition to this molecular control of electrical activity, the electrical activity also feeds back onto the molecular system.
"So it's a feedback system that acts as an additional timekeeper."
That means the electrical signal actually goes both ways. Timed patterns of biological activity, like digestion, heart rate or hormone production, also help to regulate the response or electrical conductivity that controls those very behaviours. It is what the researchers described as a newly revealed "inverse relationship".
Whereas before, biologists were thinking of the electrical activity as being an output function, "now it seems that it's both an output and an input", Dr Gunsalus said.
