Clock stops on NSF biological timing center, but the momentum carries on

By Fariss Samarrai

After 11 years of groundbreaking research and more than $14 million in direct funding from the National Science Foundation, the NSF Center for Biological Timing, a multi-disciplinary, multi-institutional research center headquartered at U.Va., is, in effect, closing its doors as a center later this year. The important work it has spearheaded in research and education will continue.

Photo by Rebecca Arrington

(left) Carla Green, a biology professor and center researcher, and Michael Menaker, U.Va’s Commonwealth Professor of Biology and one of the center’s founders

“NSF funds its science and technology centers for a maximum of 11 years, and after that period, the funding discontinues,” said Michael Menaker, U.Va.’s Commonwealth Professor of Biology and one of the center’s founders. “As the center closes, our researchers will continue their work with current sources of individual funding. We also are seeking new grants from other sources, including the National Institutes of Health.

“We’ve been very fortunate to have this center based at U.Va. It’s been a great collaborative project for focused research in one of the most important areas of biology.”

The NSF money, $1.3 million per year, provided infrastructure support for the center and seed money for individual researchers, who seek additional funding for their projects. This has allowed the investigators to work individually while pooling their resources through collaborations with the center’s researchers at five other institutions.

“No question, each researcher has been able to accomplish more individually because of this network of shared work and resources,” Menaker said.

The Center for Biological Timing focuses on researching circadian rhythms, the biological clocks that keep time for the human body and all organisms on Earth. These internal oscillators help us sleep, keep us awake, control our energy levels, affect our growth, aging, our moods. They play a large role in determining when plants flower, when cells divide, when animals mate. Circadian rhythms were set in motion early in the history of life on the planet, tied through evolution to the astronomical cycles that effect Earth’s environment, the rise and setting of the sun, the passing of seasons.

Research in biological timing has implications for many areas of human life, from jet lag to shift work. A better understanding of the internal clock could reduce accidents due to fatigue. Researchers also are investigating ways to deliver drug treatments for cancer and other diseases, timed to the peak rhythms of body clocks. This new area, chronopharmacology, holds a great deal of promise for more effective medicine, Menaker said.

Until the 1990s, little was known about the mechanisms underlying circadian rhythms. Today, scientists know a great deal about biological clocks at the molecular level, and much of this learning has come from the work of researchers affiliated with the Center for Biological Timing. The center brought together geneticists, molecular biologists, endocrinologists and statisticians from Brandeis University, Rockefeller University, Northwestern University, the Scripps Institute and U.Va.’s basic and medical science departments.

The Center for Biological Timing was established in 1991, after U.Va., Rockefeller and Northwestern submitted a joint funding proposal to NSF. A few years before that, several researchers at U.Va. got the idea moving with a $2 million start-up grant from the Board of Visitors, through its Academic Enhancement Program.
“Local funds were the key to initiating the center,” Menaker said. “We were able to bring together people from the biology department and the Medical School and soon realized we were onto something big. It all started with a little money from the University to kick-start a few people with a great idea for collaboration.”

Currently there are 28 NSF Science and Technology Centers around the country. The concept is to encourage and fund exploration in new areas and build bridges among disciplines and institutions. Centers offer the research community a means for embarking on long-term scientific and technological research, to explore better ways to educate students, and to ensure timely transition of research and education advances to society.

“We’ve accomplished this on all accounts,” said Gene Block, U.Va. vice president and provost and director of the center. “This was one of the first multi-university grants at U.Va., and it taught us how to work effectively across institutional boundaries. The center raised the national visibility of the University in biological and medical research, and gave us reputational leverage in the U.S. as well as in Europe and Japan.

“We also created novel outreach and collaboration models for integrating university research with K-12 education,” Block said. “Throughout our center history, high school teachers have been coming to our labs and participating in research. They have gone on to present this first-hand learning to their students. We also have sent our researchers and educators to the schools. This has demonstrated our larger role in the community.

“Most importantly, the center’s scientific accomplishments have been spectacular. We’ve done some high-risk research that has paid off greatly; some of it has fundamentally changed our understanding of biological processes.”

One of the center’s biggest advances was the development of a mutant mouse that allowed for the early identification of the gene involved with setting the biological clock. This was groundbreaking work that led to the discovery of other genes that regulate the body’s periodic cycles.

Researchers at the U.Va. School of Medicine have been investigating the neuroendocrine system and how the release of hormones are tied to oscillations of the body clock and reproduction. This research helps to explain how exercise, sleep and aging affect human metabolism, and how internal biological clocks affect hormones and fertility.

In 1997 and 1998, the highly regarded journal Science ranked the findings of center researchers among the top 10 in biological research breakthroughs.

“The center’s biggest accomplishment is our work in unraveling the molecular mechanism underlying the generation of circadian oscillation,” Menaker said. “We’ve provided the genetic tools to understanding the physiology of biological clocks.”

“We have been able to determine, at the molecular level, the cogs that control the timing of the clock,” said Carla Green, assistant professor of biology. Green uses the retina in the eyes of frogs to study the mechanisms of the circadian clock at the molecular level. “We’ve gone from knowing almost nothing, to having a great deal of insight.”