PROJECT SUMMARY / ABSTRACT
Feeding is one of the most fundamental animal behaviors, and circadian feeding patterns are influential on health
and longevity. Many of the dietary interventions (DI) that improve healthspan have been shown to act through
circadian control, yet the molecular links connecting circadian rhythms and DI remain unclear. DI such as
intermittent fasting may only be effective in times when the animal normally eats. Thus, understanding the
natural circadian pattern of feeding, and the mechanisms that regulate the circadian control of hunger, is critical
toward designing more effective DI. Using new methods that allow undisturbed real-time measurements of food
consumption, locomotor activity, and sleep, we use Drosophila as a model system to identify and investigate
genes that underlie the temporal patterning of feeding cycles. These studies take advantage of available fly
populations for genome-wide association (GWAS) mapping of quantitative trait loci and use a novel genome-
wide epistatic (GWES) approach to search for epistatic interactions between markers. These results will be
further analyzed with systems biology network models that we have constructed from publicly available
Drosophila data including co-expression, protein-protein interaction, transcription factor- and microRNA-target
relationships, and genetic interactions. If successful, our studies will: 1) characterize circadian feeding behavior
in Drosophila; 2) pinpoint particular gene variants that modulate them; and 3) determine gene function in
underlying patterned feeding. Our proposed studies offer the unique opportunity to define natural feeding
patterns and to harness the variation in natural feeding patterns to study circadian feeding regulation at the
molecular level. Since many genes involved in circadian and energy-sensing pathways are conserved across
organisms, the identification of genetic mechanisms underlying the regulation of innate circadian feeding
behavior has the potential to: 1) better our understanding of the basic biology of the relationship between
circadian rhythms and DI in promoting healthy aging and 2) inform translational studies of DI across species.