Sleep neuron control of starvation resistance

• Applicant: Professor Dr. Henrik Bringmann
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 495901211

The molecular and cellular mechanisms underlying the vital functions of sleep in promoting health are not well understood. This is surprising since sleep is essential and sleep disorders are highly prevalent in industrialized societies, posing a massive unsolved medical and economic challenge. Sleep crucially requires sleep-active neurons that depolarize during sleep and that inhibit neuronal wakefulness circuits. The nematode Caenorhabditis elegans is an important model system to study basic biological processes including aging, stress resistance, and sleep at the cellular and molecular level. Like many other animals, C. elegans displays sleeping behavior. We previously showed that C. elegans possesses a key sleep-active neuron called RIS. Impairing RIS genetically or optogenetically leads to virtually complete and highly specific sleep loss. RIS impairment dramatically shortens survival and increases the progression of aging phenotypes during larval developmental arrest, but the underlying signaling pathways, effectors, and mechanisms through which RIS supports survival and counteracts aging phenotypes during developmental arrest are not understood. In this project we will study how the RIS neuron supports survival during starvation-induced developmental arrest in the L1 larva. We will test the hypothesis that RIS impacts signaling pathways and effectors that are known to control starvation resistance. We will investigate, which of the signaling pathways and effectors that control starvation resistance interact with RIS by performing genetic survival screening. We will study which of the signaling pathways and effectors that are crucial for starvation survival are controlled by RIS and solve underlying mechanisms. This project will thus result in a molecular and mechanistic understanding of the signaling pathways and effectors that are controlled by sleep-active neurons during starvation and will thus allow solving molecular and cellular links between sleep, survival and aging phenotypes.

• DFG Programme: Research Grants