Investigating the impact of toxic proteins known as dipeptide repeat proteins on cellular changes in C9orf72 MND.
PhD Student: Charlotte Gale
Principal Investigator: Dr Ryan West
Lead Institution: University of Sheffield
MND Association Funding: £93,409
Funding dates: October 2023 - March 2027
About the project
Mutations in the C9orf72 gene are the most common genetic cause of MND and lead to the production of 5 toxic proteins called dipeptide repeat proteins (DPR’s) , which accumulate in neurons. It has previously been found that two of these five DPRs cause the structural framework that gives a cell structure and shape (cytoskeleton), to become disorganised. Using fruit fly models of C9orf72 MND, this project aims to investigate the theory that some DPR’s bind to proteins involved in regulating the cytoskeleton and cause them to stick together in clumps in the cell. This may cause disorganisation of the cytoskeleton in nerve cells and lead to neurodegeneration. It will use drug-screening facilities to screen existing drugs which are known to stabilise the cytoskeleton as potential therapeutic treatments for MND. In addition to identifying potential drugs for the treatment of MND this study will also help unravel biological mechanisms underpinning the disease.
What could this mean for MND research?
Understanding the causes of MND are vitally important when trying to find new treatments. This project will look into understanding some of the cellular changes that happen within C9orf72 MND. This can then lead to finding therapeutic targets for new potential drugs which could treat MND.
Resources
Project code: 906-792
