Despite the fundamental importance of sleep, the cellular function of sleep remains controversial. Sleep is recognized to be conserved across species, and in recent years sleep research has been extended to model organisms that provide powerful tools for genetic analysis. This project focuses on identification of genes and signaling pathways that control sleep behavior using the roundworm C. elegans as model organism. The principal investigator and her undergraduate students at California State University Northridge, a primarily undergraduate Hispanic-serving institution, have shown that exposure to environmental stresses can trigger sleep in C. elegans. Further, they demonstrated that stress-induced sleep is beneficial, and they have begun to identify several components of a genetic pathway that mediates this beneficial effect. This project expands on this work and illuminates the mechanism through which epidermal growth factor signaling contributes to stress-induced sleep. Additionally, the project uses cutting-edge molecular techniques to identify other genetic pathways critical in the regulation of stress-induced sleep. The broader impacts of this CAREER award include Full Immersion Research Experience (FIRE), a course the principal investigator redesigned with the goal of giving students an original research experience, and the integration of this lab course with the investigator's research program on sleep.

The identification of a sleep state in C. elegans that is triggered by conditions, such as noxious heat or tissue damage, suggests that perturbation of cellular homeostasis may contribute to sleep drive. Stress-induced sleep (SIS) in C. elegans may represent an ancestral state that evolved to promote recovery following environmental stress or infection. In more complex organisms, SIS may be coordinated with circadian regulation, acting to counteract perturbations of homeostasis known to be associated with prolonged wakefulness. The aim of this proposal is to characterize the genetic pathways that promote SIS. The principal investigator has shown that stress-induced sleep is dependent on Epidermal Growth Factor (EGF) receptor activation within the ALA neuroendocrine cell; however, the mechanism by which stress initiates EGF signaling is not known. The first aim of this project is to investigate how and, for the purposes of sleep regulation, in which tissues cellular stress is monitored. Because EGF family ligands are produced as transmembrane precursors that must be processed for release of soluble ligand, it is likely that EGF-dependent sleep is regulated by stress-induced ectodomain shedding. The second aim of this project is to determine from which cell(s) EGF is shed in response to stress, and to characterize a candidate protease that has been identified in an RNAi screen for sleep defects. The third and final aim of this project is to identify novel components of SIS via an unbiased forward genetic screen.

Agency
National Science Foundation (NSF)
Institute
Division of Integrative Organismal Systems (IOS)
Type
Standard Grant (Standard)
Application #
1553673
Program Officer
Edda (Floh) Thiels
Project Start
Project End
Budget Start
2016-03-01
Budget End
2021-02-28
Support Year
Fiscal Year
2015
Total Cost
$575,543
Indirect Cost
Name
The University Corporation, Northridge
Department
Type
DUNS #
City
Northridge
State
CA
Country
United States
Zip Code
91330