The skin is the primary interface between animals and their external environment. The skin maintains its structural integrity throughout the life of an organism while providing passive and active defenses against external challenges. While understanding of skin development has advanced rapidly in recent years, less is known of how the mature skin is maintained in adult life, including how it heals wounds. More broadly, the mechanisms that maintain mature tissues are still relatively poorly understood. The overall goal of this research program is to understand at the molecular level how a simple skin layer is repaired and maintained during adult life. The system of choice is the skin of the nematode C. elegans, a relatively simple and experimentally tractable model for skin layers. The C. elegans skin comprises a simple epidermal epithelium and associated basal and apical extracellular matrices, the basement membrane and the cuticle. Previous studies have how the mature skin responds to injury and repairs itself. This work led to the discovery of genetic regulators of adult skin maintenance; loss of function in such genes does not affect skin development but results in progressive adult-onset degeneration of the adult skin. Future studies will extend these approaches to dissect how the mature epidermis is maintained in normal and perturbed conditions. The epidermis and extracellular matrices of the skin function as an integrated unit in biogenesis, maintenance and repair. The proposed work will also investigate how the epidermis and extracellular matrix communicate in tissue maintenance and wound repair. These studies will also address the roles of an extracellular matrix lipid layer in formation and repair of the skin permeability barrier. The resulting insights should advance knowledge of skin biology relevant to several aspects of human health, including normal wound healing, chronic wounds, and skin fibrosis in hypertrophic scarring.
Skin wounds are acute stresses that can be life-threatening unless efficiently repaired. Wounding of barrier epithelia such as the epidermis causes loss of bodily fluids and can result in opportunistic infections at the wound site. Biomedically important pathologies of wound healing range from excessive wound healing (hypertrophic scarring and keloid) to non-healing chronic wounds and diabetic ulcers. This project uses a simple model of skin wound healing in the nematode C. elegans to understand how epidermal tissues detect and repair damage.
