"The skin has many protective functions, acting as a barrier to physical and biological threats from the external environment while regulating water loss and body temperature. Loss of the normal skin function results in inflammation and associated diseases such as psoriasis, alopecia and ichthyosis. The skin is highly-enriched in lipids and fatty acids, which can be converted by lipoxygenase (LOX) enzymes to bioactive mediators, termed eicosanoids. LOXs are a family of non heme iron enzymes of which several isoforms are present in skin. A role for several LOX isoforms in regulating epidermal integrity has been proposed, however, the detailed mechanisms involved are unknown. We recently found that LOXs can generate novel lipids comprising eicosanoids attached to membrane phospholipids in immune cells, and preliminary evidence has shown that similar lipids are present in healthy mouse skin, but the detailed structures and functions of these are yet to be characterised. This fellowship will investigate the hypothesis that esterified eicosanoids generated by LOX are involved in the physiological and pathophysiological regulation of the epidermis. Novel esterified LOX products will be structurally characterised using mass spectrometry and chromatographic approaches in both healthy mouse skin, mice deficient in a LOX isoform and a series of recombinant epidermal LOX enzymes. Purified lipid standards will be synthesised for quantification and studies of biological action. Finally, studies using wild type mice and a strain with an inflammatory hair loss phenotype will determine the role of esterified eicosanoids from LOX in regulating epidermal physiology and disease. The proposed studies will utilise genetic, chemical and structural biochemistry approaches to increase our understanding of skin physiology and may lead to design of novel treatments for inflammatory skin disorders."