ROS and SIK regulation of Stress-Induced Sleep

A proposed function of sleep is to couple the activity of different metabolic pathways with an animal’s energetic needs. This requires constant communication between sleep promoting neurons/circuits and peripheral tissues. The molecular mechanisms underlying this communication remain unclear. Previously, we demonstrated that salt-inducible kinases (SIKs) play a key role in coordinating sleep with lipid metabolism. I added to this by using the roundworm Caenorhabditis elegans and various omics methods to investigate different molecular mechanisms in which SIKs regulate sleep. This work has led me to propose that when animals are under conditions of high energy demand such as stress, reactive oxygen species (ROS) levels serve as a signal for sleep need. Using C. elegans as a model of KIN-29/SIK- regulated sleep, I tested this hypothesis in the following chapters. Chapter 1 characterizes SIK proteins in the context of sleep, gives an overview of redox signaling in sleep behavior and ends in describing why C. elegans is well suited for answering my research questions. In Chapter 2, I show that KIN-29/SIK modulates mitochondrial redox signaling to regulate stress induced sleep. In Chapter 3, I present the findings of phosphoproteomic profiling performed on kin-29 loss-of-function mutants and potential sleep targets identified by my analysis. Lastly, in Chapter 4 I conclude my work by discussing the broader implications of my findings and future research directions to be explored.

Level thesis:degree_level

Doctorate Degree

Year dc:date.issued

2026

Author dc:creator

• McIntire, Pearson

Advisor dc:contributor.advisor

• van der Linden, Alexander

Committee members dc:contributor.committeemember

• Mastick, Cynthia
• Kim, Jung Hwan
• Riddle, Misty
• Raizen, David
• Caplovitz, Gideon

Language dc:language.iso

en_US, English

Repository record dc:identifier.uri

https://scholarwolf.unr.edu/handle/11714/11921

OAI identifier oai:identifier

oai:scholarwolf.unr.edu:11714/11921