Understanding the earliest changes that happen within motor neurons when TDP43 stops working properly.
PhD Student: TBC
Principal Investigator: Dr Ashkay Bhinge
Lead Institution: University of Exeter
MND Association Funding: £131,786
Funding dates: October 2025 - March 2029
About the project
In both sporadic MND and familial MND, one of the main markers of disease is changes to the behaviour of a protein called TDP43 within cells. All proteins that are made in cells are made on a production line, and TDP43 plays an important role early on in this manufacturing process. In MND, TDP43 stops working at its correct place in the protein production line, which can cause errors to the proteins being made. When this happens in motor neurons it can make them more vulnerable to damage and death. In this project, researchers are using their newly established model of sporadic MND to explore how TDP43 causes problems within motor neurons when it stops working properly. Healthy human cells are grown into motor neurons in the lab, and TDP43 is instructed to misbehave in the same way that it does in MND. The researchers have already observed what protein products are most affected when TDP43 stops working properly in the protein production line, and in this project, they will explore how these changes contribute to MND. They will reverse the changes to proteins caused by TDP43 not working properly and observe whether this restores the health of the motor neurons. This will include observing changes to the survival, structure and function of the motor neurons. The aim of this project is to understand the earliest changes that happen within motor neurons when TDP43 stops working properly, as it does in MND.
What could this mean for MND research?
By identifying the most important changes that are caused by TDP43 malfunctioning, and investigating if the reversal of these changes improves the health of the motor neuron, the researchers may be able to identify novel targets for new therapies for MND.
Project code: 2406-792