Using Drosophila to study and identify new therapies for mitochondrial disease. (360G-Wellcome-204715_Z_16_Z)

Mitochondrial diseases are a group of genetically heterogeneous and progressive disorders which can affect multiple organs. There are currently no curative treatments, with palliative treatments only available for some patients. A better understanding of the molecular pathology of mitochondrial diseases is needed to accelerate the development of new treatments. Evidence from in vivo models suggests that mitochondrial disease may be a result of adaptations to mitochondrial dysfunction during development, which when corrected prevent mitochondrial disease pathology. I plan to test this using Drosophila melanogaster, inducing mitochondrial dysfunction by decreasing levels of respiratory Complex I at different stages of development, in the whole fly and in specific tissues. Using this approach I will study the effects of mitochondrial dysfunction at the molecular, physiological and behavioural level. I will also test if mitochondrial disease can be rescued by restoring mitochondrial function. Finally, I will develop fly models of mitochondrial disease to establish a high-throughput screening methodology to identify novel therapies for mitochondrial disease. This combined approach will broaden our knowledge surrounding the effects of mitochondrial dysfunction and use new and existing models of mitochondrial disease to identify novel therapies. Thus, it has the potential to greatly impact mitochondrial disease research.