Dresden International Graduate School for Interdisciplinary Life Sciences

Project 5

Modulation of collagen cuticle properties by sleep

Collagen is an important component of many biological coat structures that confers a protection from the environment such as mechanical injury or infection by pathogens. Protective collagenous structures have to be able to adapt to changing physiological conditions and react to environmental stimuli. For example, nematodes produce thicker and more sturdy cuticle structures upon environmental stress and human skin shows increased signs of aging when a subject is deprived of sleep. Here, we will study the modulation of the materials properties of the epidermal cuticle in C. elegans, a free-living nematode. C. elegans synthesizes its cuticle during development and repairs it after wounding. Notably, the animals sleep during both cuticle synthesis and repair109,110. Analysis performed in preparation for this project indicates that disrupting sleep causes defects in the cuticle structure: we found a shortening of furrows (Figure P5A-B), a decreased resistance to hypochlorite treatment (Figure P5C), and possibly a reduction in Young’s modulus, which would indicate a decreased resistance to deformation Figure P5D). While these results establish a link between sleep and cuticle robustness, the mechanisms by which sleep supports cuticle formation and robustness remain unclear. 

This project aims to elucidate how sleep contributes to epidermal cuticle formation and robustness. Our key hypotheses are that sleep: i) reallocates resources, such as metabolites required for energy production and macromolecule biosynthesis (carbohydrates and amino acids), from neurons and muscles to the epidermis for cuticular component synthesis, and ii) provides the quiescence necessary for proper cuticular structure formation, such as for cellular ultrastructural arrangement, self-assembly and cross-linking of collagen. Such elaborate cuticular structures may not be formed precisely during wakefulness, when the body undergoes vigorous movements. To test these hypotheses, we employ precise genetic and optogenetic tools to control cuticle synthesis and sleep and study the effect on cuticle formation.