Martha Gillette brings her biochemical understanding of how cells signal one another to examining the body's biological clock in rats. The clockwork, it turns out, drives not only circadian rhythms of sleep and wakefulness, but almost every function in any living organism, including such functions as eating, drinking, body temperature fluctuation and hormone secretion.
"What I totally love about clocks is that they're so biological," says Gillette. "They are so universal. Vast mats of blue green algae in the Pacific Ocean have them; even single-celled organisms have them. Cells that have six-hour division cycles can keep track of the 24-hour cycle. Clocks tell plants when to flower, they tell migratory animals when to travel."
Understanding What Makes the Biological “Clock” Tick
Martha Gillette’s grin can easily light up a room, but behind that thousand-watt grin is a determination that could stop a freight train.
Although Gillette knew from a young age that she would be a scientist, she faced more than her share of obstacles in the course of her career.
Having completed her post-doctoral training, Gillette arrived at the University of Illinois with her husband, Rhanor, and their two young children, in 1978; a time when spousal hiring was unheard of. The university didn’t “want any appearance of nepotism,” she remembers. “Dual careers were unlikely options.”
Jim Heath, then the head of what is now known as the Department of Molecular and Integrative Physiology, gave Gillette the title of visiting assistant professor. Rhanor gave her some space and equipment in his lab and she set to work.
It is the rare creature indeed that can begin as a visiting assistant professor and successfully leap the chasm from a visiting position to a tenure-track one. But between her drive, her brains and, she says, her luck, Gillette pulled it off. She now is not only a full professor but has been head of the Department of Cell and Developmental Biology for the last eight years.
In the beginning the Gillettes collaborated on several successful projects and grants involving sea slug neuroscience. Soon, however, a grant reviewer noted that “If Mrs. Martha Gillette thinks she deserves the princely sum of $18,000 , she better write her own grants.”
“That sum was not princely even then,” says Gillette with a grin. Still, the remark did get her attention and she realized she needed to chart her own course, separate from Rhanor’s.
Gillette brought her biochemical understanding of how cells signal one another and applied that to examining the body’s biological clock in rats. The clockwork, it turns out, drives not only circadian rhythms of sleep and wakefulness, but almost every function in any living organism, including such functions as eating, drinking, body temperature fluctuation and hormone secretion.
“What I totally love about clocks is that they’re so biological,” says Gillette. “They are so universal. Vast mats of blue green algae in the Pacific Ocean have them; even single-celled organisms have them. Cells that have six-hour division cycles can keep track of the 24-hour cycle. Clocks tell plants when to flower, they tell migratory animals when to travel. Clocks tell the liver when to make liver enzyme; and the clock in the brain (suprachiasmatic nucleus, or SCN, in mammals) synchronizes the whole body.”
Most other researchers in the field of biological clocks were doing experiments on live animals and treating the SCN as a black box. Gillette, on the other hand, put a slice of the SCN in a life-support dish and showed that it kept “ticking” for three days, demonstrating that the clock was endogenous and not dependent on external stimuli. Her work very soon became known as the “clock in the dish.” Later, Gillette also became well known for deciphering the signal sent from the eye to the clock.
“People really didn’t know how the clock worked,” says Gillette. “For example, how did light from the outside world affect the internal clock? I was in the right place doing something unusual in that field.”
Gillette’s first paper on the “clock in the dish” was published in 1985. In 1986, she was promoted to visiting associate professor, which came with a room of her own and the proper standing to write her own grants.
“To succeed outside of the usual path, you need opportunity—which means space and equipment. Rhanor really fostered my success, at a time before people recognized I could be an asset. Art DeVries also helped, offering me “hot” space to work with radioactivity,” says Gillette.
Because of the novelty of her approach, Gillette started to receive research grants, which attracted students, which resulted in papers. She began to make a name for herself and for her research. Still, as a non-tenure track faculty member, Gillette was something of a stepchild in the department. In the late 1980s, when two positions were posted, she applied for both. One was molecular neuroscience and one was computational neuroscience.
“I know I can be one of those,” Gillette remembers thinking. Although not the first choice for either position, Gillette ended up getting the molecular neuroscience position in what is now Cell and Developmental Biology and in the College of Medicine.
“I never thought I wouldn’t have a position,” she said with a huge grin. “I was sure I was the right person for the job.”
In 1990, 12 years after she arrived on campus, Gillette was appointed associate professor, a tenured position. In 1993, she was named full professor. Today she not only heads the Department of Cell and Developmental Biology, but also is a professor in the Department of Molecular and Integrative Physiology, holds an appointment at the Institute for Genomic Biology, and is an affiliate of the Beckman Institute. Gillette collaborates extensively with colleagues across the campus and at other institutions, something she especially enjoys.
True to her sunny disposition, Gillette does not dwell on the struggles she faced. In fact, Gillette points out that her route through academia—unconventional as it was—suited her, since she had no worries about the “tenure clock” while she had small children at home. And she enjoyed support, from her husband and friends, and the department offered the opportunity to write for grants.
In turn, Gillette has provided support for the numerous students, particularly women, who have come through her laboratory. In 2004, she was awarded the Mika Salpeter Lifetime Achievement Award by Women in Neuroscience at the Society for Neuroscience annual meeting in recognition of her mentoring of numerous female medical scholars and graduate and postdoctoral researchers.
Gillette also believes that her role as a researcher requires her to help educate the public about the importance of basic research.
“It is reasonable to a certain extent to think about the applications of research and to demystify the connection between research and medical advances,” says Gillette. “But there is no question that the reason U.S. science has been pre-eminent for so long is its investment in basic research science. Without that funding we will shortchange ourselves and pay a big price 10 or 20 years from now.”
Despite important responsibilities as an administrator, mentor, and advocate, it is still basic research that makes Gillette tick. She makes time for this passion by working at the bench in the evenings and continuing to supervise her laboratory, which has eight doctoral students, two postdoctoral fellows, one technician, and three undergraduates.
There are still so many things to understand about the biological clock, says Gillette. For example, while the SCN generates approximately 24-hour rhythms of physiology and behavior, those oscillations are influenced by a dynamic cycle of neurochemical signals. In fact, says Gillette, the image of the clock is not exactly accurate because the mechanism is not a series of gears, but a dynamic system, always changing with respect to what signals touch it. Unraveling those signals take much of Gillette’s attention.
In addition, some clocks interact with one another, so if one is out of balance it can affect others. Circadian rhythms, for example, are important in regulating sleep and so Gillette has become expert in sleep disorders. Her group found out, for example, that sleep centers in the brain can alter timing of the clock, possibly an effect of sleep deprivation.
Recently, Gillette has been investigating the idea that perhaps the signals that adjust the clock are the same that the brain uses to make memories, which raises the interesting question of circadian plasticity; that this may be a very fundamental mechanism that all cells use.
“There are still so many interesting questions out there,” she says with a grin.