Isabella Asselstine MSc Candidate, Bendena Lab Investigating the role of neuropeptide receptor 14 (NPR-14) in Caenorhabditis elegans sleep Narcolepsy is a sleep disorder characterized by chronic fatigue and episodes of cataplexy. Through studies in human and animal models, a causative link has been revealed between narcolepsy and decreased orexin signaling. In the model organism Caenorhabditis elegans,a G-protein coupled receptor called neuropeptide receptor 14 (NPR-14) has been identified as a potential ortholog to the human orexin receptor-2 (OX2R). Previous phenotypic analyses of npr-14 knockout strains revealed a marked reduction in adult locomotion and mechanosensory stimulation compared to wildtype strains. This narcoleptic-like phenotype observed in npr-14 knockouts, along with the proposed orthologous relationship to OX2R, suggests that npr-14 is involved in the regulation of sleep in C. elegans. C. elegans displays two distinct sleep pathways: the developmentally timed sleep (DTS) pathway, and the stress induced sleep (SIS) pathway. The objective of my thesis research is to elucidate the role of npr-14 in the DTS and/or SIS pathways. This will be achieved by observing DTS and SIS behaviour in npr-14 knockout worms alone and in combination with known regulators of either pathway. Results of this research may uncover epistatic interactions between NPR-14 and components of DTS/SIS, therefore suggesting its potential position within either pathway. Successful characterization of npr-14’s role in C. elegans sleep may provide a model system in which the pathology of narcolepsy and other fatigue-presenting conditions may be explored.
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