Investigating the Role of Neuropeptide Receptor 14 (NPR-14) in C. elegans Sleep
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Authors
Asselstine, Isabella
Date
Type
thesis
Language
eng
Keyword
C. elegans , narcolepsy , npr-14 , sleep , stress induced sleep , epistasis
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Abstract
Narcolepsy is a chronic sleep disorder that affects an estimated 1 in 2,000 people in the United States and Europe, making it one of the most prevalent sleep conditions worldwide (Longstreth et al., 2009; Silber et al., 2002). Studies in human and animal models have revealed a causative link between instances of narcolepsy and decreased orexin signaling. In Caenorhabditis elegans, a G protein-coupled receptor called neuropeptide receptor 14 (NPR-14) has been identified as a potential ortholog to the human orexin 2 receptor (OX2R). npr-14 mutants display a marked reduction in adult locomotion and mechanosensory stimulation compared to wildtype strains. The narcoleptic-like phenotype observed in npr-14 mutants, along with the proposed orthologous relationship to OX2R, suggests that npr-14 is involved in the regulation of sleep in C. elegans. This work endeavours to elucidate the role of NPR-14 in the C. elegans stress induced sleep (SIS) pathway. Epistasis experiments between NPR-14 and SIS regulators LIN-3, FLP-11, FLP-24, and DMSR-1 have revealed a potential location of NPR-14 within the SIS pathway. Data suggests that NPR-14 acts downstream of LIN-3 and FLP-24, and upstream of DMSR-1 and FLP-11 during SIS. Results from this study contribute towards successful characterization of NPR-14’s role in C. elegans sleep. A greater understanding of how NPR-14 contributes to sleep in C. elegans may provide a model system in which the pathology of narcolepsy and other fatigue-presenting conditions can be explored.
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ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.