Neural regulation of sleep, appetite and energy homeostasis is critical to an animal's survival and under stringent evolutionary pressure. Dysregulation of sleep is strongly linked to obesity, diabetes, and metabolic disease. Despite the prevalence of disorders associated with metabolism and sleep, the neural and genetic processes that regulate interactions between these two systems is unclear. This proposal will investigate how genes and neurons modulate sleep in response to changes in metabolism. Flies, like mammals, potently modulate sleep in accordance with their nutritional needs. Specifically, flies and mammals suppress sleep in response to starvation, presumably to initiate food-seeking behavior. Powerful genetics in the fruit fly allow for precise characterization of genes regulating behavioral and metabolic processes. I recently carried out a neuron-specific RNA interference screen of over 1100 genes revealed numerous targets that are required for metabolic regulation of sleep. In particular, this screen isolated translin (trsn), an mRNA/DNA binding protein that is highly conserved from flies to humans. Neuron specific knock-down or mutations in the trsn locus results in flies that fail suppress sleep during starvation, but have normal energy stores trsn is highly conserved across phyla and has a putative role in mammalian metabolic function. This proposal seeks to characterize the cellular and neuroanatomical function of trsn to determine how sleep and metabolic state are integrated. This work will define a critical link between metabolism and sleep regulation, providing new avenues for investigating sleep-feeding interactions that potently impact human health. Functional investigation of genes regulating sleep-metabolism interactions will provide the groundwork for understanding metabolic regulation of behavior and further our understanding of obesity, sleep disorders and diabetes.
Dysregulation of both sleep and metabolism presents an enormous health burden throughout the world. This proposal will investigate how genes and neurons modulate sleep in response to changes in metabolism. Functional investigation of the genes regulating sleep-metabolism interactions will provide the groundwork for understanding metabolic regulation of behavior and further our understanding of obesity, sleep disorders and diabetes.
| Stahl, Bethany A; Peco, Emilie; Davla, Sejal et al. (2018) The Taurine Transporter Eaat2 Functions in Ensheathing Glia to Modulate Sleep and Metabolic Rate. Curr Biol 28:3700-3708.e4 |
| Brown, Elizabeth B; Torres, Joshua; Bennick, Ryan A et al. (2018) Variation in sleep and metabolic function is associated with latitude and average temperature in Drosophila melanogaster. Ecol Evol 8:4084-4097 |
| Yurgel, Maria E; Keene, Alex C (2018) Sleep: Helicon Cells Charge the Circuit. Curr Biol 28:R317-R319 |
| Zandawala, Meet; Yurgel, Maria E; Texada, Michael J et al. (2018) Modulation of Drosophila post-feeding physiology and behavior by the neuropeptide leucokinin. PLoS Genet 14:e1007767 |
| Keene, Alex C; Duboue, Erik R (2018) The origins and evolution of sleep. J Exp Biol 221: |
| Tauber, John M; Brown, Elizabeth B; Li, Yuanyuan et al. (2017) A subset of sweet-sensing neurons identified by IR56d are necessary and sufficient for fatty acid taste. PLoS Genet 13:e1007059 |
| Stahl, Bethany A; Slocumb, Melissa E; Chaitin, Hersh et al. (2017) Sleep-Dependent Modulation of Metabolic Rate in Drosophila. Sleep 40: |
| Stahl, Bethany A; Keene, Alex C (2017) To rebound or not to rebound. Elife 6: |
| Murphy, Keith R; Deshpande, Sonali A; Yurgel, Maria E et al. (2016) Postprandial sleep mechanics in Drosophila. Elife 5: |
| Masek, Pavel; Keene, Alex C (2016) Gustatory processing and taste memory in Drosophila. J Neurogenet 30:112-21 |
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