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. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2018. / FAU Electronic Theses and Dissertations Collection
| Identifer | oai:union.ndltd.org:fau.edu/oai:fau.digital.flvc.org:fau_40897 |
| Contributors | Yurgel, Maria E. (author), Keene, Alex C. (Thesis advisor), Florida Atlantic University (Degree grantor), Charles E. Schmidt College of Science, Department of Biological Sciences |
| Publisher | Florida Atlantic University |
| Source Sets | Florida Atlantic University |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation, Text |
| Format | 191 p., application/pdf |
| Rights | 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., http://rightsstatements.org/vocab/InC/1.0/ |
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