The University of Massachusetts Amherst
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NIH Funds Research on Human “Body Clock”

Michael Henson, a faculty member in the Chemical Engineering Department at the University of Massachusetts Amherst and the director of the campus Center for Process Design and Control, plays a key role in a four-year, $950,000 grant from the National Institutes of Health (NIH) to study the 24-hour circadian rhythm, or “body clock,” in humans. Professor Henson’s research for this four-school collaborative project involves creating mathematical models of circadian rhythm generation to better understand sleep disorders and other diseases triggered by malfunction of the 24-hour body clock.

Henson’s models simulate how some 20,000 neurons in the suprachiasmatic nucleus (SCN) region of the hypothalamus, located in the brain stem, synchronize with each other to create the circadian rhythm that helps control sleep patterns in humans and other mammals. Henson’s findings could have far-reaching impacts on studies of sleep disorders, jet lag, and other behavior related to the body clock.

“This is basic research,” explains Henson. “We don’t envision this research resulting in something that a company can use in two years. But the underlying principles of this study have a lot of applications related to important issues with the circadian rhythm in human beings.”

Henson is working with experimental biologists and other researchers at Washington University, the University of California Santa Barbara, and Colby College. The NIH grant effectively renews a similar grant awarded for $950,000 to study circadian rhythm from 2006 to 2010.

A circadian rhythm is a 24-hour cycle in biochemical, physiological, or behavioral processes controlled by the SCN. Although circadian rhythms are built-in and self-sustaining in humans, they are influenced by external cues, the primary one being daylight.

“If you’ve ever traveled overseas,” notes Henson, “you can certainly understand what we’re studying. Your body clock is thrown out of sync with the change in daylight hours you are used to, so jet lag sets in.”

Henson’s role in the project is to take data about the neurons, generated through biology experiments by his collaborators, and build models that accurately simulate how the 20,000 neurons of the SCN act as a synchronized system to produce the circadian clock. The process requires Henson’s team to analyze the experimental data, create individual neuron models with them, then incorporate these individual models in complex system models of how all the neurons work together.

An important part of Henson’s work will also be to model how this neuron synchronicity changes over time, thus creating effects such as people waking up earlier and earlier in the morning as they age.

Henson’s collaborator at Washington University is circadian biologist Eric Herzog, whose main hypothesis is that a neural transmitter called VIP, which is secreted by neuron cells, works to set up communication among the neurons in the SCN.

“The molecular-level mathematical models we develop on the computer are based on this hypothesis,” says Henson, “that VIP is the main mechanism by which these 20,000 neurons communicate. If you have all these cells doing their own thing, then they’re not going to generate a coherent overall circadian rhythm.”

One technique being used by the experimental biologists is to make actual recordings of neuron cells firing and then, from those recording, try to correlate the behavior of individual cells with each other.

“In this way, the researchers are trying to extract how all these SCN neurons might be connected,” says Henson. “It’s basically done by signal processing. In effect, researchers can listen to the recordings and say, ‘Oh, every time this cell fires this other cell fires a little bit later, so they must be connected.’”

As Henson explains, when his computer models are “robust enough,” then they will be used to tackle such important issues as sleep disorders related to circadian rhythm, the most effective way to recover from jet lag, and how to adjust the body clock in soldiers, airline pilots, surgeons, nurses, and other professionals so they can stay alert when awake for long periods of time. (January 2012)

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