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Genetic and Neural Mechanisms Regulating the Interaction Between Sleep and Metabolism in Drosophila Melanogaster

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Date Issued:
2018
Abstract/Description:
Dysregulation of sleep and metabolism has enormous health consequences. Sleep loss is linked to increased appetite and insulin insensitivity, and epidemiological studies link chronic sleep deprivation to obesity-related disorders. Interactions between sleep and metabolism involve the integration of signalling from brain regions regulating sleep, feeding, and metabolism, as well as communication between the brain and peripheral organs. In this series of studies, using the fruit fly as a model organism, we investigated how feeding information is processed to regulate sleep, and how peripheral tissues regulate sleep through the modulation of energy stores. In order to address these questions, we performed a large RNAi screen to identify novel genetic regulators of sleep and metabolism. We found that, the mRNA/DNA binding protein, Translin (trsn), is necessary for the acute modulation of sleep in accordance with feeding state. Flies mutant for trsn or selective knockdown of trsn in Leucokinin (Lk) neurons abolishes starvation-induced sleep suppression. In addition, genetic silencing of Lk neurons or a mutation in the Lk locus also disrupts the integration between sleep and metabolism, suggesting that Lk neurons are active during starvation. We confirmed this hypothesis by measuring baseline activity during fed and starved states. We found that LHLK neurons, which have axonal projections to sleep and metabolic centers of the brain, are more active during starvation. These findings suggest that LHLK neurons are modulated in accordance with feeding state to regulate sleep. Finally, to address how peripheral tissues regulate sleep, we performed an RNAi screen, selectively knocking down genes in the fat body. We found that knockdown of Phosphoribosylformylglycinamidine synthase (Ade2), a highly conserved gene involved the biosynthesis of purines, regulates sleep and energy stores. Flies heterozygous for two Ade2 mutations are short sleepers and this effect is partially rescued by restoring Ade2 to the fly fat body. These findings suggest Ade2 functions within the fat body to promote both sleep and energy storage, providing a functional link between these processes. Together, the experimental evidence presented here provides an initial model for how the peripheral tissues communicate to the brain to modulate sleep in accordance with metabolic state.
Title: Genetic and Neural Mechanisms Regulating the Interaction Between Sleep and Metabolism in Drosophila Melanogaster.
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Name(s): Yurgel, Maria E., author
Keene, Alex C., Thesis advisor
Florida Atlantic University, Degree grantor
Charles E. Schmidt College of Science
Department of Biological Sciences
Type of Resource: text
Genre: Electronic Thesis Or Dissertation
Date Created: 2018
Date Issued: 2018
Publisher: Florida Atlantic University
Place of Publication: Boca Raton, Fla.
Physical Form: application/pdf
Extent: 191 p.
Language(s): English
Abstract/Description: Dysregulation of sleep and metabolism has enormous health consequences. Sleep loss is linked to increased appetite and insulin insensitivity, and epidemiological studies link chronic sleep deprivation to obesity-related disorders. Interactions between sleep and metabolism involve the integration of signalling from brain regions regulating sleep, feeding, and metabolism, as well as communication between the brain and peripheral organs. In this series of studies, using the fruit fly as a model organism, we investigated how feeding information is processed to regulate sleep, and how peripheral tissues regulate sleep through the modulation of energy stores. In order to address these questions, we performed a large RNAi screen to identify novel genetic regulators of sleep and metabolism. We found that, the mRNA/DNA binding protein, Translin (trsn), is necessary for the acute modulation of sleep in accordance with feeding state. Flies mutant for trsn or selective knockdown of trsn in Leucokinin (Lk) neurons abolishes starvation-induced sleep suppression. In addition, genetic silencing of Lk neurons or a mutation in the Lk locus also disrupts the integration between sleep and metabolism, suggesting that Lk neurons are active during starvation. We confirmed this hypothesis by measuring baseline activity during fed and starved states. We found that LHLK neurons, which have axonal projections to sleep and metabolic centers of the brain, are more active during starvation. These findings suggest that LHLK neurons are modulated in accordance with feeding state to regulate sleep. Finally, to address how peripheral tissues regulate sleep, we performed an RNAi screen, selectively knocking down genes in the fat body. We found that knockdown of Phosphoribosylformylglycinamidine synthase (Ade2), a highly conserved gene involved the biosynthesis of purines, regulates sleep and energy stores. Flies heterozygous for two Ade2 mutations are short sleepers and this effect is partially rescued by restoring Ade2 to the fly fat body. These findings suggest Ade2 functions within the fat body to promote both sleep and energy storage, providing a functional link between these processes. Together, the experimental evidence presented here provides an initial model for how the peripheral tissues communicate to the brain to modulate sleep in accordance with metabolic state.
Identifier: FA00013163 (IID)
Degree granted: Dissertation (Ph.D.)--Florida Atlantic University, 2018.
Collection: FAU Electronic Theses and Dissertations Collection
Note(s): Includes bibliography.
Subject(s): Drosophila melanogaster
Sleep
Metabolism
Held by: Florida Atlantic University Libraries
Sublocation: Digital Library
Persistent Link to This Record: http://purl.flvc.org/fau/fd/FA00013163
Use and Reproduction: Copyright © is held by the author with permission granted to Florida Atlantic University to digitize, archive and distribute this item for non-profit research and educational purposes. Any reuse of this item in excess of fair use or other copyright exemptions requires permission of the copyright holder.
Use and Reproduction: http://rightsstatements.org/vocab/InC/1.0/
Host Institution: FAU
Is Part of Series: Florida Atlantic University Digital Library Collections.