title: Identification of genes associated with resilience/vulnerability to sleep deprivation and starvation in Drosophila.
abstract: OBJECTIVE
  Flies mutant for the canonical clock protein cycle (cyc(01)) exhibit a sleep rebound that is ∼10 times larger than wild-type flies and die after only 10 h of sleep deprivation. Surprisingly, when starved, cyc(01) mutants can remain awake for 28 h without demonstrating negative outcomes. Thus, we hypothesized that identifying transcripts that are differentially regulated between waking induced by sleep deprivation and waking induced by starvation would identify genes that underlie the deleterious effects of sleep deprivation and/or protect flies from the negative consequences of waking.
  
  
  METHODS
  We used partial complementary DNA microarrays to identify transcripts that are differentially expressed between cyc(01) mutants that had been sleep deprived or starved for 7 h. We then used genetics to determine whether disrupting genes involved in lipid metabolism would exhibit alterations in their response to sleep deprivation.
  
  
  METHODS
  Laboratory.
  
  
  METHODS
  Drosophila melanogaster.
  
  
  METHODS
  Sleep deprivation and starvation.
  
  
  RESULTS
  We identified 84 genes with transcript levels that were differentially modulated by 7 h of sleep deprivation and starvation in cyc(01) mutants and were confirmed in independent samples using quantitative polymerase chain reaction. Several of these genes were predicted to be lipid metabolism genes, including bubblegum, cueball, and CG4500, which based on our data we have renamed heimdall (hll). Using lipidomics we confirmed that knockdown of hll using RNA interference significantly decreased lipid stores. Importantly, genetically modifying bubblegum, cueball, or hll resulted in sleep rebound alterations following sleep deprivation compared to genetic background controls.
  
  
  CONCLUSIONS
  We have identified a set of genes that may confer resilience/vulnerability to sleep deprivation and demonstrate that genes involved in lipid metabolism modulate sleep homeostasis.
authors.affiliation: Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO.|Missouri University of Science and Technology, Department of Biological Sciences, Rolla, MO.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Thimgan
authors.affiliation: Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO.|Centre de Recherche en Neurosciences de Lyon, Integrated Physiology of Arousal Systems Team, Lyon, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Seugnet
authors.affiliation: Division of Endocrinology, Diabetes, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors.forename: John
authors.initials: J
authors.lastname: Turk
authors.affiliation: Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Shaw
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006706:Homeostasis / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012890:Sleep / Q000502:physiology; D012892:Sleep Deprivation / Q000235:genetics* / Q000503:physiopathology; D013217:Starvation / Q000235:genetics* / Q000503:physiopathology; D013997:Time Factors; D014851:Wakefulness / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D012333:RNA, Messenger
keywords: Drosophila melanogaster; lipid metabolism; lipid storage; microarray; sleep homeostasis; transcriptional changes