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The University of Sheffield Faculty of Medicine, Dentistry & Health Department of Neuroscience ROLE OF MITOCHONDRIA IN C9ORF72-RELATED ALS/MND Supervisor: Kurt De Vos, Andy Grierson Project: Expansions of a noncoding GGGGCC hexanucleotide repeat in the C9ORF72 gene are the most common genetic defect found to date in ALS and frontotemporal dementia (FTD). How these expansions cause disease is not known, but may involve both loss-of-function (C9ORF72 haploinsufficiency), and gain-of-function (repeatassociated non-ATG (RAN) translation, RNA toxicity) mechanisms. Mitochondria play a central role in the pathogenesis of familial and sporadic amyotrophic lateral sclerosis (ALS) / motor neuron disease (MND). Mitochondria are the main source of oxidative stress; mitochondria determine excitotoxicity because they are the key calcium-buffering organelles in motor neurons; mitochondria regulate protein homeostasis, and mitochondrial dysfunction causes ER stress; last but not least mitochondria produce most energy (ATP) required to maintain neuronal function and diminished ATP synthesis and mislocalisation of mitochondria kills neurons. In this project you will quantify mitochondrial function in loss- and gain-of-function models of C9ORF72-related ALS as well as in patient-derived cells to comprehensively test the role of mitochondria in C9ORF72-related ALS and to identify novel therapeutic avenues. This project is funded by an MNDA Prize Studentship (www.mndassociation.org). The studentship provides full support for tuition fees (at UK/EU levels) and a tax-free annual stipend (£16,000-£17,000). Start date is October 2014. Entry Requirements: Candidates must have a first or upper second class honors degree or significant research experience. Enquiries: Interested candidates should in the first instance contact Kurt De Vos ([email protected]). How to apply: Please complete a University Postgraduate Research Application form and attach at least two references to your application. To complete the application form please visit: www.shef.ac.uk/postgraduate/research/apply. Please clearly state the prospective main supervisor in the respective box and select ‘Neuroscience’ as the department. Website: http://www.shef.ac.uk/neuroscience Closing date: 3rd February 2014