Research in our lab primarily uses rodent models to understand molecular bases of circadian timing in mammals. Two major areas of interests are:
Rhythmic changes in transcription, translation and protein activity give rise to rhythms in cellular function. Temporal orchestration of rhythmic tissue and organelle function generates systems level daily changes in behavior and physiology, which are generally referred to as Circadian rhythms. Circadian rhythms have been documented in organisms from unicellular cyanobacteria to higher mammals, where they are believed to impart a survival advantage to the organism by timing behavior and physiology to the appropriate time of the day, thereby creating a temporal ecological niche.
In mammals, molecular timing mechanism or biological clock has been established to function in a cell autonomous manner. Interlocked transcription-translation feedback loops constitute the core mechanism of the biological clock. The biological clock in turn regulates transcription of a large number of genes in a tissue specific manner. A master circadian oscillator resident in the hypothalamic suprachiasmatic nucleus (SCN) orchestrates tissue specific rhythmic activities to generate organism level rhythmic behavior and physiology. Our focus is to understand the underlying regulatory mechanism that maintains a near 24hours rhythm of the core clock components and of the target output genes by using genomics, genetic and biochemical tools.
The circadian clock in most organisms is entrained to the ambient light dark cycle primarily by light perceived by the eye. Photoentrainment of the circadian clock enables us to adapt to new lighting regime resultant from change of season, jet travel, or change in work schedule. Intriguingly, circadian photoentrainment can fully function even in the absence of rod/cone fuction raising the possibility that a dedicated photoreceptor system may be involved.
Melanopsin –a G-protein coupled receptor with extensive sequence similarity to invertebrate opsins – has recently emerged as a prime photopigment candidate for circadian photoentrainment. Melanopsin is expressed primarily in a small subset of retinal ganglion cells (RGCs) that are intrinsically photosensitive. Loss of melanopsin abolishes photosensitivity of these RGCs and attenuates light entrainment of the clock. Research in our lab uses genetic, molecular biology, biochemical, electrophysiological and pharmacological approaches to elucidate the signaling cascade down stream of melanopsin and to understand how light information from rod/cone pathways and melanopsin pathway area integrated to regulate an array of non-visual photic processes in mammals.
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