Biological Clocks Pace Body’s Physiology

Buried deep within the human brain is a structure that allows the body to know what time it is and to adjust its chemistry to keep all its varied physiological processes in sync with each other.
David Earnest studies this structure, called the suprachiasmatic nucleus (SCN), a small cluster of specialized cells located deep within the brain. Earnest is associate professor in the Department of Human Anatomy and Medical Neurobiology in the College of Medicine of The Texas A&M University System Health Science Center. He also serves on the faculty in Texas A&M University’s Department of Biology and its newly formed Center for Biological Clocks Research. The center, administered through the Texas A&M Department of Biology but involving researchers from other university departments and the A&M System Health Science Center, will build upon current institutional interdisciplinary research strengths in the field of biological rhythms and the ‘clocks’ that control them.
“Researchers in the Center study organisms ranging from mammals to bacteria, but interestingly enough, no matter how complex or how simple the organism, the same basic mechanisms operate to generate 24-hour (circadian) rhythms at the molecular level,” Earnest said. “The Center will investigate to what extent biological rhythm mechanisms are conserved across different species and to what extent they differ, with the goal of understanding both critical and common elements of timing systems we call biological clocks.”
Although most of Earnest’s research has involved rodents, he has found that 24-hour biological rhythms are just as important in humans as in these rodents.
“Just like rodents and other species, humans are responsive to the daily light/dark cycle,” he observed. “It’s just that in humans, it takes stronger light, such as bright sunlight, to reset and synchronize circadian rhythms.”
Earnest’s research has focused on the signaling pathways by which light synchronizes these rhythms.
“Interestingly, and somewhat counterintuitively, the clock in the SCN is sensitive to light during the night phase of the cycle and is not sensitive to light during the daytime,” Earnest said. “We’re trying to find the ‘switch’ that turns on that sensitivity when the sun goes down, causing the light information carried by the retinal nerves to reset the SCN clock and the circadian rhythms that is regulates.”
Research into human circadian rhythms has been applied to helping travelers deal with jet lag and shift workers adjust to their schedules, but more important applications lie in the implications of such rhythms for drug treatments, such as in chemotherapy.
“For example, researchers have discovered that the efficacy of chemotherapy is influenced by the time at which it is given,” Earnest said. “Ideally, the medications should be given at the time when peak cell division occurs within the tumors that they seek to destroy, but at the time when cell division in the digestive system is at its lowest point, to minimize side effects like nausea.”
Earnest has also looked at the permanent effects of fetal alcohol syndrome (FAS) on 24-hour rhythms. Using a rodent model, this research shows that FAS disrupts rhythms, resulting in shorter sleep/wake cycles, hyperactivity and greater sensitivity to light. And he’s involved with the development of SCN cell lines in the laboratory to allow researchers to study biological clocks at the molecular and cellular level in cultures.
“We have the only such cell lines in the world,” Earnest said. “We are using them to identify which genes are involved in regulating circadian rhythms. By using an immortalized cell line, we can study how altered expression of particular genes affects the clock and use this information to construct a model of the whole animal and its biological rhythms.
“The thread connecting all our research is that there are reasons for these internal timing mechanisms,” Earnest observed. “No matter what type of organism one studies, circadian rhythms provide a temporal program that synchronizes all body processes with the external environment (such as the daily solar cycle) and provides harmony between internal processes (such immune system function, which is elevated during specific phases of the sleep-wake cycle).”
The Texas A&M University System Health Science Center provides the state with health education, outreach and research. Its five components located in communities throughout Texas are Baylor College of Dentistry, the College of Medicine, the Graduate School of Biomedical Sciences, the Institute of Biosciences and Technology and the School of Rural Public Health.