Control and functions of wounding-induced sleep in C. elegans

• Applicant: Professor Dr. Henrik Bringmann
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: from 2020 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 440875170

Sleep is a fundamental state that is essential for survival and controls many physiological processes. Sleep disorders are widespread in modern societies thus posing a massive medical and economic problem. Likely, all animals that have a nervous system sleep, as sleep has been found in species ranging from jellyfish to mammals. Sleep-active sleep-promoting neurons depolarize specifically during sleep to induce sleep by shutting down the activity of wakefulness neurons. Illness or stress can increase the need for sleep, and sleep is thought to be important for recuperation. Chronic wounds and impaired wound healing in humans present a major health problem. Despite the importance of sleep, little is known about how sleep and recuperation from wounding are linked at the molecular level. C. elegans is an established model system to study basic biological phenomena. It facilitates molecular and mechanistic analysis through its ease of maintenance, short generation time, compact nervous system, transparency and low ethical hurdles. C. elegans is an established model organism to study sleep as well as the response to epidermal wounding, two important biological phenomena that have hitherto been studied only separately in this system. It is not understood in any system how wounding induces sleep and how sleep promotes recuperation from injury. Specifically, it is not known how wounding leads to the depolarization of sleep-active neurons and it is not known how the activity of sleep-active neurons promotes recuperation. Here we provide preliminary evidence that epidermal wounding in C. elegans induces sleep, and that sleep promotes survival of the injury. We thus established a system to study how sleep and wounding interact at the molecular level. To solve how wounding and sleep interrelate in an animal, in this project we will study the interplay of sleep and recuperation following epidermal injury. We will follow these four specific aims: 1) We will reveal the mechanism by which known wounding response pathways trigger sleep. 2) We will analyze the global transcriptomic changes underlying sleep induction following wounding to identify novel pathways underlying the interplay of sleep and wounding. 3) We will find out how sleep modulates the wounding response at the cell biological level. 4) We will identify key wounding response pathways that interact genetically with sleep loss. Together, this project will provide a comprehensive understanding of molecular and cellular signaling pathways that lead from injury to sleep-active neuron depolarization, and how the activity of a sleep-active neuron promotes recuperation. As both sleep and the wounding response are highly conserved in evolution, this study will provide a roadmap for investigating the interplay of sleep and wound healing in other organisms including humans.

• DFG Programme: Research Grants