Two interacting processes, the circadian clock and a homeostatic sleep drive, which reflects both the quality and quantity of waking experience, regulate sleep. The circadian clock has been heavily studied and the molecular process underlying it is well understood. The sleep homeostat, on the other hand, is poorly understood and our knowledge of the molecular processes governing it is incipient at best. Discovery of the gene period, which encodes an integral component of the molecular clock and displays oscillatory expression reflecting normal clock function, allowed for real-time monitoring of the clock's molecular mechanism in vivo using a bioluminescent luciferase reporter (per-luc). In contrast, the best marker of sleep drive is electroencephalogram delta band power, which neither completely reflects sleep drive nor serves as a functional component of the sleep homeostat. Thus, the primary goal of this project is to use a specific set of parameters defining an ideal homeostatic marker to actually identify markers of homeostatic sleep drive. Previous attempts to identify genes with a role in the sleep homeostat through transcriptomics have largely suffered from a lack of specificity. Substantial changes in gene expression can often be observed in specific circuits at times when global profiling reveals naught. This proposal leverages the Allada lab's expertise in gene expression profiling of small, genetically defined populations of neurons to identify transcripts that reflect changes in homeostatic drive in sleep relevant areas of the fly brain. In addition, I am proposing several novel strategies to improve detection of homeostatic genes by eliminating circadian influence and manipulating waking experience prior to homeostatically driven recovery sleep. Candidate transcripts will be subjected to secondary screening to eliminate genes that do not play a functional role in homeostatic drive. Finally, I propose to develop novel tools for in vivo monitoring of the molecular process governing sleep drive to facilitate future inquiry into the mechanisms underlying sleep.

Public Health Relevance

Sleep is a highly conserved behavior across the animal kingdom, but we have very little understanding of its purpose. The circadian clock and an ill-defined homeostatic drive generated by extended wakefulness regulate sleep, but the molecular process at the root of the homeostatic drive is completely unknown. My proposal focuses on targeted gene expression profiling and functional validation to identify potential molecular correlates of homeostatic sleep drive and develop tools for further investigation of this process in the fly, Drosophila melanogaster.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32NS110183-01
Application #
9683290
Study Section
NST-2 Subcommittee (NST)
Program Officer
He, Janet
Project Start
2018-12-01
Project End
2020-11-30
Budget Start
2018-12-01
Budget End
2019-11-30
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
160079455
City
Evanston
State
IL
Country
United States
Zip Code
60201