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Anyone who’s ever flown internationally is familiar with jet lag. It’s the disorienting feeling of suddenly finding your body in another time zone. But jet lag isn’t just in your head.
“Jet lag is a disorder of the whole body,” said Justin Blau, a biologist at New York University whose team studies circadian rhythms in the brain cells of fruit flies. “It’s not just your brain telling you to wake up at the wrong time of day, it’s also your liver clock telling you it’s getting ready to deal with food at the wrong time of day.”
Like researchers all over the world, Blau’s team is seeking to better understand what makes cellular clocks tick – how the gears fit together. At their weekly lab meeting, Blau and his team gathered in his office to talk about a new study by biologists at Blau’s alma mater, Cambridge University. The upshot, he says, is simple.
“Clocks are more complicated than we thought,” Blau said.
Until now there’s been a general consensus in the field that the DNA in a cell’s nucleus is the spring that drives the clock. But Ahkilesh Reddy and John O’Neill at Cambridge looked for timekeeping in red blood cells – a human cell with no nucleus at all. What they found was a chemical called peroxiredoxin, which allowed the cells to maintain rhythms for days with no outside stimulus – and no DNA spring. Reddy says that’s a surprising discovery.
“The status quo for many years has been that although non-transcriptional rhythms – those not requiring DNA – have been seen in very primitive bacteria, no one thought that you’d be able to see the same things in complex organisms,” Reddy said.
Matthew Kayleigh, a post-doctorate student in Blau’s lab at NYU, says the discovery is groundbreaking.
“It’s a bit like you know how a car works, and these people are saying there’s like another motor in a car,” Kayleigh said.
The Cambridge team didn’t just look at human cells. They found the same chemical, serving the same function, in a species of algae. Ben Collins, another post-doc and the NYU lab’s circadian rhythm expert, says that this kind of circadian rhythm may date back to the very origins of life on earth, because while the genes are different, this newly discovered chemical marker is the same in algae, flies, and humans.
“This is something that links all those sets of genes together, and it suggests maybe the original clock in the first organism was something like this,” Collins said.
But although the clock teaches about the past, it has immediate health implications in the future. And that brings us back to jet lag. If peroxiredoxin turns out to be the body clock’s original spring, Cambridge University’s Ahkilesh Reddy says it could give doctors a new way to wind the human clock – without having to mess with genetics
“Even though gene therapy has been bandied around for many years, affecting gene function is very difficult, whereas things like peroxiredoxin are easy to target with drugs,” Reddy said.
That’s further down the line. In the meantime, scientists are looking at just how many species have this metabolic clock in their cells. That means Blau’s NYU team will keep looking at flies, and keep asking questions.
