Probing the circadian clock in zebrafish larvae with in situ single cell transcri

California Institute Of Technology, Pasadena CA

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Abstract

DESCRIPTION (provided by applicant): Disruption of normal sleep and circadian rhythms is a major factor affecting drug addiction and recovery. It has recently been shown that essentially all cells in our body have a circadian clock. Using zebrafish as a model system, we will apply and optimize a new technology in single cell gene expression analysis to characterize the diversity of behaviors in circadian clocks amongst cells in an organism. In particular, we will apply a method to profile mRNA expression levels in situ to measure the abundance of 25 circadian clock genes simultaneously in each cell of intact zebrafish larvae. This will provide a global assessment of circadian rhythms in all cells of an intact vertebrate animal at an unprecedented level of detail and robustness. We will test several hypotheses regarding circadian clock gene expression in vivo and its modulation by drugs associated with addiction and reward. We will also test the hypothesis that modulating circadian rhythms affects behaviors associated with reward and addiction. These studies could reveal novel circadian mechanisms that affect drug abuse and addiction and may lead to new therapies for these disorders. If successful, this technology can be extended to other model organisms to study large-scale gene expression changes associated with many complex behaviors.