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Fall 2019

“I had a full-on freak out. I realized the clock defect was genetic.”

Martha Vitaterna helped discover the first molecular piece of the mammalian clock. By Amanda Morris

Image: Michael Goss

As the morning sun peeks over the edge of Lake Michigan, 41 mice in a pitch-dark laboratory climb off their wheels and nestle into their bedding. The lab is quiet. And then, there is a clicking. Click, click, slide. Click, click, slide.

Mouse No. 25 is still awake. As he clicks along his running wheel, a pen spastically jolts up and down a rotating strip of paper. Martha Hotz Vitaterna, then a doctoral student in the lab, will find the recording the next day.

“Mouse No. 25 was the founder mouse for the Clock mutant line,” says Vitaterna ’92 PhD, a research professor of neurobiology at Northwestern’s Weinberg College of Arts and Sciences. “At the time, I didn’t know what I had on my hands.”

Before Vitaterna started her work, researchers did not think it was possible to find the genetic basis for circadian rhythms in mammals. When she applied to graduate school, three labs had just cloned the gene at the heart of flies’ circadian rhythms.

“Genetics as a tool to understand clocks was fascinating to me,” Vitaterna says. “But a professor at another school said, ‘Looking for single-gene mutations will never work in mammals; they are way too complicated.’  ”

But Vitaterna, whose parents were also academics, was not one to get discouraged. “I grew up knowing that women are as intellectually capable as men,” Vitaterna says, “and confident enough to ignore someone who dismissed my ideas.”

She pursued a doctorate at Northwestern, where Professor Fred Turek encouraged her to look for clock genes in mice.

Vitaterna provided mice with running wheels and exposed them to normal light/dark cycles for a few weeks. Then, she turned off the lights entirely.

“By running on their wheels, the mice could tell me what time of day they thought it was,” she says.

Typically, a mouse’s internal clock is about 23.7 hours a day. But mouse No. 25 experienced a 24.7-hour day. After getting the mouse to breed, Vitaterna found the same pattern in some of the mouse’s offspring.

“I had a full-on freak out,” she says. “I realized the Clock defect was genetic. It was one thing to be allowed to do this far-out, long-shot project, but then to have it work was an incredible experience.”

In 1994 Science journal published the results of Vitaterna’s experiment, which was the first molecular piece of the mammalian clock. Since then, research with Clock mutant mice has shown that circadian rhythms are important to almost every physiological process — from sleep to digestion to mood and more.

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