How the Body’s Trillions of Clocks Keep Time

Carrie Partch was at the tail end of her postdoc when she made the first discovery. The structural biologist was looking at a database of human proteins, noting those that shared a piece with the ones she’d been studying. “I was just sort of flipping through it thinking, ‘I should know all of these,’” she recalls. “Then this one came up, and it had a different domain architecture than I’d ever seen.” She looked further into the protein, called PASD1, whose function was unknown. She found that among the few proteins it resembled was one called CLOCK. And that made her sit up straighter — because CLOCK is at the heart of a very large, mysterious process.

Not that long ago, as Partch knew, it had become clear that nearly every cell in nearly every tissue in the body keeps time. Every 24 hours, responding to a biochemical bugle call, a handful of proteins assembles in the cell’s nucleus. When they bind to each other on the genome, they become a team of unrivaled impact: Under their influence, thousands of genes are transcribed into proteins. The gears of the cell jolt into motion, the tissue comes alive, and on the level of the organism, you open your eyes and feel a little hungry for breakfast.

These timekeeping protein complexes, which take some of their cues from a part of the brain that responds to light and darkness, are known as circadian clocks. By some estimates, they regulate the expression of 40 percent of the genes in the body. Researchers are accumulating evidence that circadian clocks have deep effects on everything from fetal development to disease. Circadian clocks are so ubiquitous, and so important to the function of individual cells, that biologists whose research doesn’t overtly connect to a clock are becoming aware of how it might impact their work. “More and more they are stumbling into clock components,” said Charles Weitz, a molecular biologist at Harvard Medical School. “It doesn’t surprise me.”

Very few cells lack a clock, but they include biologically compelling examples like embryonic stem cells and cancer. In an effort to discern how the molecular clock works — and why, sometimes, it appears to stop — Partch decided to look closer at PASD1. As she and her colleagues recently revealed in a paper in Molecular Cell, PASD1 may be a switch that explains how cells as different from each other as cancers and sperm precursors escape the daily rhythms that govern the trillions of other cells in the body. It gives researchers a deep look at the secrets of how the cell ticks. More here: How the Body’s Trillions of Clocks Keep Time

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