Investigating the role of the endoplasmic reticulum in Drosophila and mammalian models of mitochondrial

State primary research question and where appropriate the primary hypotheses being tested The aim of this PhD is to investigate the endoplasmic reticulum unfolded protein response (ER UPR) in response to mitochondrial dysfunction in Drosophila and mouse models of the mitochondrial disease Leigh syndrome (LS). Investigating the neuronal UPR and mechanisms behind its activation in models of LS will improve our understanding of the pathogenesis of the disease, and potentially lead to the identification of therapeutic targets for preventing disease progression, of which there are currently none. Hypothesis: The UPR is activated in models of mitochondrial disease, and is a therapeutic target for preventing neurodegeneration Aim 1: To investigate the UPR and underlying mechanisms in Drosophila models of mitochondrial disease Aim 2: To investigate the UPR and underlying mechanisms in mouse models of mitochondrial disease Aim 3: To investigate the UPR as a target for treating neurodegeneration in mouse models of mitochondrial disease