Harmer Lab:NIH

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Molecular analysis of Arabidopsis circadian regulation

Funded by National Institute of General Medical Sciences

Senior Personnel

Project Summary

Circadian rhythms, found widely in nature, are produced by an internal oscillator or clock and modulate most aspects of physiology in diverse eukaryotes. These rhythms provide an adaptive advantage, likely due to the accurate phasing of clock outputs with regards to rhythmic changes in the environment. Although clock components are not conserved across higher taxa, functionally analogous intertwined transcriptional feedback loops are crucial to clock function across eukaryotes. The study of circadian clocks in multiple model systems therefore provides us with insights that are relevant to diverse organisms.

The long-term goal of this proposal is to understand the molecular basis of circadian rhythms in eukaryotic cells. The work described here will fundamentally advance our understanding of the architecture underlying the circadian network in Arabidopsis thaliana and in addition define general principles governing precise temporal regulation of gene expression. Building upon our previous studies in which we identified novel regulators of the circadian clock, we will use genomic, biochemical, genetic, and mathematical modeling approaches to appropriately place these proteins in the circadian system.

Arabidopsis is an ideal model system for these experiments. It is a complex eukaryote using many of the gene and chromatin regulatory pathways found in mammals, yet has a compact genome with readily identifiable regulatory sequences. Prior studies have defined circadian patterns of gene expression and the distribution of chromatin marks and chromatin regulatory proteins on a genome-wide scale. Mutants are available for most genes in the genome, and Arabidopsis tolerates mutations in chromatin regulatory pathways that are lethal to other higher eukaryotes.