Date of Award
Doctor of Philosophy (PhD)
Cell & Molecular Biology
The increasing prevalence of metabolic disease in modern society has accelerated our need to understand factors that may be contributing to its development. Both circadian disruption and sleep deprivation are associated with metabolic dysfunction. Thus, for my dissertation I sought to gain insight into this association by studying the genetic and neural basis of interactions between circadian rhythms, sleep and metabolism. The relative simplicity of fly neuroanatomy and physiology, vast array of available genetic tools, and conservation across many organisms, makes Drosophila melanogaster an ideal model to dissect complex interactions between physiological systems. Through our studies we identified a novel role for a molecule that regulates feeding behavior, Neuropeptide F (NPF), in the circadian system. We found that NPF drives circadian gene expression of the detoxification gene sex-specific enzyme 1 in a peripheral metabolic tissue, possibly to coordinate consumption of toxins with their removal. Our results support a role for NPF in synchronizing behavior and metabolism to ensure circadian coherence and promote survival. In addition, we studied the interaction between sleep and metabolism by evaluating whether alterations in sleep cause metabolic dysfunction or are the result of shared molecular pathways. The insect equivalent of norepinephrine, octopamine, promotes wake in flies by signaling through insulin-producing neurons. We determined that although sleep and metabolic neural circuitry intersect, the octopamine signaling pathway regulates sleep and metabolism independently. This dissertation highlights the great power of Drosophila as a model organism to investigate complex interactions between different biological systems.
Erion, Renske, "Regulation of Sleep and Circadian Rhythms by Metabolic Neuropeptides" (2014). Publicly Accessible Penn Dissertations. 1271.