Molecular and cellular mechanisms underlying the mutual control of a sleep neuron and a lysozyme

• Applicant: Professor Dr. Henrik Bringmann
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 562134364

Sleep is essential and supports vital physiological processes of the brain and body. Sleep disorders are highly prevalent in modern societies, thus posing a massive unsolved health problem. However, despite its importance, little is known about how sleep is regulated at the molecular level. Central to the induction of sleep are sleep-active neurons that depolarize during sleep to inhibit neuronal wakefulness circuits. Sleep is evolutionarily conserved and can be studied across different animal models. Caenorhabditis elegans is advantageous for sleep research as it facilitates a molecular-mechanistic dissection. We previously showed that sleep in C. elegans depends crucially on a single sleep-active neuron called RIS. Thus, the single RIS neuron provides a unique chance to study the molecular biology of sleep-active neurons. Via single-cell sequencing, we have previously determined genes that are specifically expressed in RIS. One of these RIS-expressed genes encodes a lysozyme, whose deletion leads to more sleep. The mechanisms behind sleep regulation by the lysozyme are not understood. Here, we provide preliminary evidence that the lysozyme not only controls sleep, but that the lysozyme itself is regulated by RIS. This suggests the hypothesis that the lysozyme is part of a homeostatic sleep regulatory mechanism. For this project, we will test this hypothesis and will solve mechanisms underlying the mutual control of the RIS sleep neuron and the lysozyme. This project will thus provide molecular mechanisms of how a sleep neuron is regulated by a lysozyme and how the sleep neuron in turn controls the lysozyme.

• DFG Programme: Research Grants