How do our bodies keep time?

Nearly every cell in your body is a daily clock. Cellular clocks track the hours of the day through a molecular mechanism that regulates daily protein production. Collectively, these cells form an adaptive system that is essential for producing daily rhythms in behavior and physiology. In our lab, we investigate how individual clock cells communicate to coordinate with one another to maintain the adaptive function of the system.

Circadian timekeeping is disrupted by our 24/7 society. Shiftwork is a part of life for more than 15% of Americans, and research indicates that shiftwork causes disease. In fact, the FDA has classified shiftwork as a Class 2A carcinogen due to its association with increased risk of cancer. In addition, shiftwork is associated with metabolic syndrome, diabetes, cardiovascular disease, reproductive complications, neurodegeneration, and neurological dysfunction. The key to treating these diseases is to better understand what makes circadian clocks tick, how they control cellular function, and their mechanistic links to pathology. 

Towards this goal, our lab investigates circadian networks at the system level. In particular, we focus on the master clock in the mammalian brain, the suprachiasmatic nucleus (SCN). Although a small part of the hypothalamus, the SCN influences nearly every system in your body. The SCN receives photic cues directly from the retina, which it processes and transmits to other clock tissues in the brain and body. This ensures that the various clock tissues throughout the body are coordinated with one another and the environment. Because the SCN is a master control center, investigating its function is essential to understanding circadian timekeeping.

A key objective for our research is to map the functional architecture of the SCN. Like other cells, SCN neurons and astrocytes express daily rhythms when they are isolated from one another. But the SCN is unique in that its cells communicate with one another. Intercellular communication within the SCN has been shown to synchronize, amplify, and stabilize the cellular rhythms of its constituents. In other words, SCN cells interact so that they form a whole greater than the sum of its parts. How SCN cells communicate is not clear, but gaining deeper insight into SCN circuitry and signaling is an important goal for our research. 

To better understand circadian timekeeping, we focus on several key questions:

How do SCN neurons communicate with one another?
Do distinct subclasses of SCN cells have specific properties and/or roles in the network?
How does the SCN control other tissues of the body?
How is the SCN and circadian system altered by changes in the environment?
How do changes in clock function contribute to disease?
What factors influence clock plasticity and the response to environmental disruption?

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