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Photo of Douglas McMahonLike Clockwork

Anyone who has been brain-numbed by jet lag or stultified by a sleep disorder knows just how powerfully the brain's internal biological clock controls daily life.

UK researcher Douglas McMahon, one of three recipients of the 2000 University Research Professorship, a competitive annual award of $35,000 to fund a year of full-time research, plans to study just how genes drive this daily biological clock.

"We call this mechanism the 'circadian' clock from the Latin for 'about a day,'" says McMahon, an associate professor in the College of Medicine's Department of Physiology. "The circadian timing function of the brain is of fundamental importance for brain physiology, for behavior and, ultimately, for human health."

To study this brain function, McMahon's team created an artificial gene that linked the biological clock gene sequence to that of a fluorescent marker protein (called Green Fluorescent Protein, or GFP) that makes jellyfish glow. Because the two gene sequences were connected, when the natural biological clock gene "turned on," so did the artificial glowing gene, allowing the team to observe the gene's activity. The UK Transgenic Mouse Facility inserted this gene into live mice so that McMahon's team could monitor changes in the isolated biological clock nucleus and eventually in awake, behaving animals.

"It's a bit like turning each biological clock cell into a glow-in-the-dark watch where we can read the molecular time on its daily clock," says McMahon.

He hopes to take this a step further and introduce more fluorescent color channels for genes. Through cross-breeding of the glowing mice, his team hopes to achieve different-colored tags for multiple genes in a single mouse—a rainbow of gene activity whose spectrum would indicate the overall gene expression state of the brain.

This gene-tagging process provides the basis for McMahon's upcoming research, through which he will work to achieve a clearer understanding of the molecular basis of the biological clock and to report ongoing changes in gene expression in a live animal.

He hopes that this research will contribute to clinical treatments for people whose biological clock is affected, by seasonal affective disorder (SAD), sleep disorders, and jet lag, and also help other researchers adapt clinical applications for monitoring disease processes and molecular-based therapies in the brain.

Jonathan Riggs