Myofibroblast metabolism in tissue repair and fibrosis (360G-Wellcome-211438_Z_18_Z)

The overall goal of this project is to investigate whether biochemical switching and metabolic reprogramming has a role in the development of myofibroblasts and subsequent scar formation in fibrosis. Therefore my hypothesis is that in scleroderma, fibroblasts reprogram their metabolism to accommodate the enhance demand of energy required to differentiate and produce more scar tissue (ECM). And that altered energy metabolism due to dysregulated signalling networks closely linking metabolism with fibroblast differentiation are critical to the establishment of myofibroblasts and contributes to the development of inflammatory-driven scar formation and tissue fibrosis. I wish to build upon the preliminary studies and determine how energy metabolism influences the behaviour of myofibroblasts in fibrosis and ask if the pathological aspects of cell behaviour be attenuate with specific inhibitors. The three specific aims of my vacation scholarship are to examine: 1. Mitochondrial morphology and mitophagy in cultured control and fibrotic fibroblasts and assess any changes in fission and fusion using mito-tracker dyes. 2. Glycolysis and Mitochondrial Respiration in cultured control and fibrotic fibroblasts using the Seahorse metabolic flux analyser. 3. The impact inhibitors and activators of key profibrotic pathways on glycolysis and mitochondrial respiration in cultures of control and fibrotic fibroblasts.