Jimo Borjigin

Circadian Rhythms

Scientists in the Borjigin lab are interested in understanding the cellular and molecular mechanisms that govern circadian rhythms. The pineal gland expresses melatonin, one of the most dramatically regulated hormones, which, because it links the body's physiological processes to the daily cycle of sunlight and darkness, provides an ideal model system for circadian-rhythm research. The scientists are focusing on two aspects of pineal rhythms: first, they are trying to identify the intracellular and extracellular molecules that control or influence pineal rhythms, and second, they are examining the mechanisms by which neuronal and humoral inputs lead to nightly production of melatonin.

Utilizing a sensitive subtractive hybridization technique, the researchers have isolated night pineal cDNAs encoding the serotonin N-acetyltransferase (NAT), a novel PIneal Night-specific ATPase (PINA), and Patched 1 (Ptc1). NAT is the rate-limiting enzyme of melatonin formation; PINA is a novel, alternatively spliced, pineal, and night-specific form of the Wilson disease (WD) gene; and Ptc1 is a tumor suppressor and a receptor for Hedgehog proteins that play a key role in embryonic development. The group's work indicates that the nightly production of all three messages are controlled primarily by cAMP signaling and that the protein products are sensitive to light stimulation during dark periods. In addition to NAT, PINA, and Ptc1, the scientists have identified a number of other diurnally regulated mRNAs in the rat pineal that appear to be important in pineal circadian functions. Understanding the role of these diurnal intracellular molecules in pineal circadian function is one of their main goals.

To facilitate molecular dissection of circadian-rhythm pathways, the group has established methods to examine in vivo the influences of extracellular molecules on pineal circadian rhythms. They have also developed techniques to express foreign proteins in pineals of live animals at high efficiency, which will allow the Borjigin lab to explore the mechanism of action of newly discovered genes.