In mammals, circadian (ca. 24h) clocks in the brain and throughout the body orchestrate daily patterns of physiology and behavior. These daily patterns persist under constant conditions as "circadian rhythms". The Welsh lab studies circadian rhythms in cells using bioluminescence imaging to monitor clock gene expression. We are interested in the autonomy, heterogeneity, and coupling of cellular circadian clocks, particularly the "master" clock cells of the brain, the neurons of the suprachiasmatic nucleus. We are also interested in how defects in these mechanisms may contribute to sleep and circadian rhythm disorders in humans, including mood disorders.
In collaboration with the Dulcis Lab, Welsh Lab members are studying the effects of photoperiod on protein and gene expression within the mammalian suprachiasmatic nucleus (SCN). Pictured below is a coronal view of the SCN stained for arginine vasopressin (red), period 2 (green) and vasoactive intestinal peptide (blue), three proteins involved in the integration and communication of light signals.
Welsh Lab members also study the function of the cellular clock through imaging of tissue slices and dispersed cells. We often use PER2::LUC reporter mice created in by Dr. Joseph Takahashi, in which the rhythmically expressed Per2 circadian clock gene is replaced by a fusion of Per2 with the gene encoding firefly luciferase. The cells of these mice glow with a circadian rhythm, allowing us to study the function of the clock in single cells by monitoring their faint bioluminescence with highly sensitive, low-noise cameras. The videos below show circadian rhythms of PER2::LUC bioluminescence recorded from mouse SCN neurons in a cultured slice (left) and in dispersed cell culture (right).