Characterising myeloperoxidase oxidation on lipids and lipoproteins

Lipids are key biological molecules essential to life. Lipidomics is the characterisation and study of the complete lipidome of a biological system (fluid, cell, tissue, organism). The diversity of lipids is driven by their structural backbone, variable fatty acyl lengths and the degree of unsaturation and can span thousands of different species. One of the key mechanisms in our innate immunity is the ability for neutrophils to respond to acute inflammatory stimuli, and if needed, initiate a response against foreign pathogens including bacteria. This response typically results in the generation of reactive molecules via myeloperoxidase (MPO). Compounds generate via MPO include hypochlorous acid; a cytotoxic oxidant used to kill bacteria. Hypochlorous acid can cause oxidative damage to the surrounding area and is notable for its high reactivity with lipids. However, comprehensive characterisation of the products of this reaction with the lipidome has not been reported. This project aims to characterise these lipids across a large domain of lipid classes, using mass spectrometry and ultimately determine their down-stream impact on cellular stress and death.