Investigation of ataxin-2 as a therapeutic target for frontotemporal dementia and motor neurone disease

Frontotemporal dementia (FTD) is the second most common form of dementia in people under the age of 65. Due to the fact that it usually affects people of working age, the effect on their families is devastating. We know that up to 40% of patients have a family history of disease which indicates that genetics plays a large role in the aetiology of this condition. The most common genetic cause of FTD is known as a repeat expansion mutation in the gene C9orf72 and is found in 1 out of 12 patients. Unaffected people have between 1 and around 30 repeats of the 6 DNA bases GGGGCC. In affected patients this number ranges from around 500 to in excess of 4000. Interestingly, this mutation can also cause motor neurone disease (MND) and is the most common cause of this condition. The repeats are translated into 5 different dipeptide repeat proteins (DPRs) that form into pathological aggregates in FTD/MND. The SPB lab have generated expression constructs that express >1000 DPR repeats. Ataxin-2 knockout has recently been shown to be protective in a mouse model of FTD/MND. This project will involve the investigation of the role of ataxin-2 on the phenotype induced by >1000 DPR repeats in cell culture. In addition, we have recently generated Drosophila models expressing the >1000 repeat construction and these will also be used to investigate ataxin-2. This project will overall address whether ataxin-2 is a viable therapeutic target for FTD/MND.

Entry Requirements:
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.