2016 Conference on Computational Modelling with COPASI
Manchester Institute of Biotechnology, 12th – 13th May, 2016
1 - University of Manchester, UK
Keywords: Skin, Eicosanoids, Inflammation, Computational Modelling, Medical Systems Biology
Inflammatory responses in the skin play a major role in a number of pathophysiological conditions such as sunburn, dermatitis and psoriasis. A major contributor to the regulation of inflammation is a class of potent bioactive lipid mediators, known as the eicosanoids. Eicosanoids are derivatives of the polyunsaturated fatty acid arachidonic acid. The family of eicosanoids includes more than 100 bioactive lipid species, including prostaglandins, leukotrienes, thromboxanes and prostacyclin. These mediators are known to be involved in various stages of the inflammatory response, and their biochemistry has been targeted for the development of therapeutics, including non-steroidal anti-inflammatory drugs (NSAIDs). Here, we introduce a mechanistic mathematical model of the network of cutaneous eicosanoids that includes multiple substrates and enzyme isoforms. This kinetic model of lipid mediator dynamics will be analysed using an efficient Monte Carlo ensemble modelling method to explore the landscape of potential model behaviours. The results of the study will allow for more targeted experiments to be designed, will permit a detailed mapping of the lipid networks contributing to skin inflammation, and ultimately will support the design of new interventional strategies to combat skin disease.