Satchin Panda
 Assistant Professor, The Salk Institute

e-mail: satchin@salk.edu
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Molecular Mechanism of Circadian Rhythms in Mammals
We study the molecular basis of circadian timekeeping in mammals. A major focus of our research is to understand the phototransduction mechanism of specialized light sensitive ganglion cells in the retina which photo-entrain the master circadian oscillator resident in the hypothalamic SCN. A second area of research in the lab revolves around understanding the regulatory mechanisms which maintain a near 24 hours molecular rhythm in core oscillator components that ultimately produce overt rhythms in physiology and behavior.

Light entrainment of the circadian clock helps organisms to readjust their activity- rest cycle to the changing day length of different seasons. In mammals, loss of rod and cone cells responsible for conscious vision does not affect photoentraiment, while loss of both eyes abolishes all light response, suggesting presence of additional ocular photoreceptor(s). A novel photopigment called melanopsin is a prime candidate for this new photoreceptor. Melanopsin is expressed in a small subset of retinal ganglion cells (RGCs) that are intrinsically photosensitive. These RGCs make a unisynaptic connection to the oscillator neurons of the SCN. We are employing several genetic, electrophysiological, and biochemical approaches to characterize the mechanism of light perception and signal transduction by melanopsin.

The hypothalamic SCN functions as a master circadian oscillator, orchestrating temporal coordination of oscillators in peripheral organs. Several oscillator components identified in the past few years work together to constitute cell autonomous interlocking transcription–translation feedback loops. We are using genomics, genetics and biochemical approaches to identify additional components of the oscillator in order to fully understand the mechanisms that ensure precise functioning of the biological clock. Finally, we are using similar techniques to unravel the underlying regulatory networks that orchestrate molecular rhythms throughout the body to produce rhythms in physiology and behavior.

     Panda S, Nayak SK, Campo B, Walker JR, Hogenesch JB, Jegla T. (2005). Illumination of the melanopsin signaling pathway. Science 307(5709):600-04

     Rudic RD, McNamara P, Curtis AM, Boston RC, Panda S, Hogenesch JB, Fitzgerald GA. BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis. (2004). PLoS Biol. 2(11):e377. Epub 2004 Nov 02.

     Sato TK, Panda S, Miraglia LJ, Reyes TM, Rudic RD, McNamara P, Naik KA, FitzGerald GA, Kay SA, Hogenesch JB. (2004). A functional genomics strategy reveals Rora as a component of the mammalian circadian clock. Neuron. 43(4):527-37.

     Panda S, Provencio I, Tu DC, Pires SS, Rollag MD, Castrucci AM, Pletcher MT, Sato TK, Wiltshire T, Andahazy M, Kay SA, Van Gelder RN, Hogenesch JB. (2003). Melanopsin is required for non-image-forming photic responses in blind mice. Science. 301(5632):525-7. Epub 2003 Jun 26.

     Panda S, Sato TK, Castrucci AM, Rollag MD, DeGrip WJ, Hogenesch JB, Provencio I, Kay SA. (2002). Melanopsin (Opn4) requirement for normal light-induced circadian phase shifting. Science. 298(5601):2213-6.

     Panda S, Antoch MP, Miller BH, Su AI, Schook AB, Straume M, Schultz PG, Kay SA, Takahashi JS, Hogenesch JB. (2002). Coordinated transcription of key pathways in the mouse by the circadian clock. Cell. 109(3):307-20.

     Panda S, Hogenesch JB, Kay SA. Circadian rhythms from flies to human. (2002). Nature. 417(6886):329-35. Review.

Satchin Panda received his Ph. D. in Macromolecular, Cellular and Structural Chemistry from The Scripps Research Institute under the direction of Dr. Steve A. Kay. He did his postdoctoral training with Dr. John B. Hoenesch at the Genomics Institute of Novartis Research Foundation, San Diego.