New Study Reveals Molecular Basis of Jet Lag

In a pioneering study, researchers from the Oxford Sleep and Circadian Neuroscience Institute, in collaboration with F. Hoffmann La Roche, have identified a novel gene that acts as a buffer on the effects of light on the body clock. The study, led by Russell Foster and Stuart Peirson, investigated the molecular effects underlying clock entrainment by light. They observed widespread gene expression changes in the suprachiasmatic nucleus of mice following a pulse of nocturnal light. The results published in Cell by Jagannath, Butler et al., reveal a key role for salt inducible kinase 1 (SIK1) and CREB-regulated transcription coactivator 1 (CRTC1) in clock re-setting. An entrainment stimulus causes CRTC1 to coactivate CREB, inducing the expression of Per1 and Sik1. Sik1 then inhibits further shifts of the clock by phosphorylation and deactivation of CRTC1. Thus negative feedback by Sik1 provides a homeostatic mechanism conferring stability on the clock. However, this also means that adaptation to a new environment will be gradual; the basis of jet lag. Understanding the regulation of circadian entrainment may one day lead to the development of drugs that modulate the body clock. Since circadian disruption is a common feature of several mental illnesses, including schizophrenia and bipolar disorder, such drugs may have widespread utility. The Oxford Sleep and Circadian Neuroscience Institute is funded by a Wellcome Trust Strategic award to Russell Foster, Kay Davies and Guy Goodwin and involves researchers from across Oxford including the departments of Physiology Anatomy and Genetics, Psychiatry, the Oxford Institute of Biomedical Engineering and the Nuffield Department of Clinical Neurosciences.