Circadian control of feeding is critical for animals to properly adapt to their environment, and for optimal development. However, the nature of this interaction and its relationship to metabolism is poorly understood. C. elegans has proved to be an extremely powerful model for understanding the molecular basis of feeding behavior, but it is unknown whether C. elegans feeding is under circadian control. Although circadian locomotory rhythms were described in C. elegans previously (1), these observations have been difficult to replicate, and no rhythmically expressed clock or clock-output genes in C. elegans have been identified. We set out to not only investigate the yet unidentified circadian clock in C. elegans, but to also explore the interaction between circadian clocks, metabolism and feeding behaviors. Since circadian transcripts exhibit rhythmic oscillations, genome-wide expression profiling experiments are a powerful approach to identify clock and clock-output genes. We used microarrays and a series of data analysis algorithms to identify circadian-regulated genes under photo- and thermocycling conditions in C. elegans. We identified subsets of candidate clock-output genes that exhibit robust rhythmic expression with 24 hr periodicity under either light-dark or warm-cold conditions, as well as in constant dark-dark or cold-cold conditions following entrainment. Our results indicate that thermocycles directly evoke a global expression response broader than photocycles, and that a subset of genes undergo cycling in a circadian manner. Verification of microarray data via qRT-PCR suggests that these genes may represent bona fide cycling genes. These sets include molecules predicted to regulate metabolic processes, suggesting that feeding - an activity closely related to energy metabolism - may be under circadian control. Preliminary results suggest that
tax-2, which is important for thermo- and phototaxis (2) is necessary for the cycling of these genes. We have also developed a reporter assay system to monitor rhythmic circadian gene expression, and we are planning to use this system in genetic screens to define the core clock components. Moreover, we are determining whether feeding behavior is under circadian control, and whether food signals can entrain the clock. Since it is likely that the molecular components of the C. elegans clock are distinct from those of other organisms, this work is also expected to provide information regarding the evolution of circadian clocks. 1) Saigusa et al, 2002; Simonetta & Golombek, 2007; 2) Coburn et al, 1996; Ward et al, 2008.