A hexanucleotide expansion mutation in the C9orf72 gene is the most common genetic cause of both Frontotemporal Dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS).  There are three proposed mechanisms leading to neurodegeneration downstream of C9orf72 repeat expansion; 1/ haploinsufficiency, 2/ formation of RNA-foci and 3/ accumulation of toxic dipeptide repeat proteins (DPRs) translated from the expansion via RAN-translation. Previous studies have shown this mutation triggers the integrated stress response (ISR) and that the ISR in turn increases RAN translation, creating a toxic cascade. Based in the labs of  Dr Ryan West and Dr Scott Allen at the Sheffield institute for translational neuroscience (SITraN), an award winning centre of excellence for the study of neurodegenerative diseases and drug-discovery, the successful applicant  will use a combination of Drosophila models and patient-derived iNPC models to explore mechanisms leading to activation of the ISR downstream of C9orf72 toxicity. In addition they will capitalise on SITraN’s established track record of drug-screening to explore therapeutic approaches surrounding the ISR.

We are particularly keen to support researchers with career development in line with the research development concordat and will actively support those keen on applying for career development fellowships. 

Candidates are strongly encouraged to contact Ryan (r.j.west@sheffield.ac.uk) and Scott (s.p.allen@sheffield.ac.uk)  to discuss the project prior to application.

Closing Date: 16th August 2024

3 years Fixed term 

Start Date: October 2024 (flexible with discussion)

This project is funded by the Alzheimer's Society