| Only one species wears a watch. But if you listen closely, there's ticking going on everywhere in the animal kingdom. Most life on Earth runs on a 24-hour clock, known as a circadian rhythm, that's tied to the planet's rotation around its axis. Animals, plants, worms, fish and even some bacteria are driven by circadian rhythms that link their biology with the sun, moon or tides. This rhythm influences almost every aspect of our biology. It controls when we sleep and when we wake. It regulates body temperature, hormone levels and the immune system. When the rhythm is thrown off, such as when we travel across time zones on a red-eye or stay up all night, it can leave us feeling weary and exhausted for days. Sometimes the impacts are larger: Overnight work shifts, which force workers to sleep during the day and stay awake at night, have been linked to diabetes, heart disease and some cancers. But how can our human cells keep time if they can't all sense light? The master clock, a small region of the mammalian brain known as the suprachiasmatic nucleus, takes light cues from the sun and syncs the body's cells to the correct time of day. (The clock function is more distributed in birds and reptiles.) Aided by advances in DNA sequencing in the late 20th century, scientists who study biological rhythms, known as chronobiologists, began to uncover the genes that code for the proteins — gears, essentially — that run the clock. And powerful imaging techniques have helped them home in on what these proteins look like and how they work. In our cells, every morning at dawn, two proteins known as CLOCK and BMAL1 link up and bind to different spots on our DNA to regulate the production of other proteins relevant to daytime living. Every night, four other proteins — PER1, PER2, CRY1 and CRY2 — bind to CLOCK and BMAL1 to pull them off the DNA, essentially shutting down that machinery. This complex of six proteins cycles day and night, every day of the year, for your entire lifetime. A deeper, molecular-level understanding of how our circadian rhythm works could pave the way toward regulating it with drugs to treat jet lag or help people adjust to night-shift work. Imagine wandering a new country upon arrival, at your home time of 4 a.m. — not bedraggled and foggy, but refreshed and composed! What's New and Noteworthy Carrie Partch, a biochemist at the University of California, Santa Cruz, has spent decades scrutinizing the gears that keep the internal clock running. Starting with her graduate work, she has meticulously mapped the structures of proteins in the mammalian circadian clock and how they move during the day/night cycle — and what changes can speed up, slow down or silence the clock. In the process, she's discovered how much important biology emerges from proteins' unstructured or dynamic regions. For example, her team found that the protein CRY1 stops BMAL1 by binding to its moving, disordered tail. If that tail has a mutation, it messes up the clock. Because organisms tick along reliably, pathogens can evolve to use their hosts' circadian rhythms to their own advantage. Malaria parasites, for example, reproduce inside their host's red blood cells — and their developmental timing tracks the host's circadian rhythm. This suggests that cycles of infection and immunity could reflect the time of day. It's possible that invaders could gain an upper hand by slipping in when the clock-driven immune system is not on high alert, or by actively altering proteins involved in the host's circadian timing. The most basic circadian clock known to science is found in single-celled cyanobacteria, which use three proteins to rhythmically track day and night. Recently, scientists found out that cyanobacteria can also track and respond to seasonal changes, as daily sunlight increases in summer and shrinks in winter. For example, cyanobacteria exposed to shorter day lengths showed adaptations to cold weather, such as marked changes in the composition of their cell membranes. But when researchers deleted the genes that were involved in circadian rhythm, the cyanobacteria lost this seasonal sense, which suggests that their circadian clocks are linked to their seasonal ones. | 
