Investigating why the waste disposal system within neurones is disrupted in people living with C9orf72-MND.
PhD Student: Olivia Houghton
Principal Investigator: Dr Sarah Mizielinska
Lead Institution: King's College London
MND Association Funding: £117,560*
Funding dates: February 2021 - July 2024
*Supported by the Bruce Wake Charitable Trust
About the project
Defects in the C9orf72 gene can produce repetitive proteins which disrupt the cells' waste disposal system (called autophagy). If waste is not cleared effectively from brain cells, it builds up and clumps together affecting cell function and eventually leading to cell death. Autophagy requires certain proteins to be transported between the nucleus and cytoplasm. This project will investigate 1) how repetitive proteins disrupt autophagy and how this is related to the dysfunction of transport, 2) how that overlaps with loss of the C9orf72 protein and how the autophagy disruption affects the clearance of key disease-related cargo and 3) the therapeutic potential of autophagy inducers. This will hopefully help design new therapies to prevent the death of brain cells and thus the normal functioning in C9orf72-related MND.
What could this mean for MND research?
This project is looking to uncover more about the biological mechanisms that happen within MND, specifically C9orf72-MND. It will increase our understanding of why the waste disposal system goes wrong in MND and also look at ways to be able to prevent or correct the damage being done. This will hopefully lead to potential new therapies which will prevent the death of brain cells.
Project code: 896-792
