Understanding TDP-43 aggregation
Dr Martina Hallegger, Prof Nicolas Lux Fawzi, Prof Jeetain Mittal and Assistant Prof Yuna Ayala, The University of Oxford, Brown University, Texas A&M University and St. Louis University
Discovery Network
Validate therapeutic targets
April 2025 - May 2028
£981,501.00
Summary
TDP-43 is a protein that plays an important role in the assembly line that converts information stored in our DNA into molecules called RNA, which are used as the template for making the proteins within our cells. While TDP-43 is known to be dysregulated in about 97% of people living with MND, we still don't know enough about the RNAs that TDP-43 regulates in neuronal cells, and the factors that contribute to the formation of TDP-43 aggregates that are often seen in motor neurons affected by MND.
The Hallegger team have previously shown that certain genetic mutations in TDP-43 can impair the protein’s interaction with RNA, which is known to have a negative effect on neuronal function. With this Discovery Network award, the team will combine artificial intelligence and computation tools with cell models and cutting-edge sequencing techniques to investigate how neurons respond to TDP-43 dysfunction and how this changes TDP-43’s ability to regulate RNA.
Why this research is important
There is an urgent need to identify and better understand the earliest cellular defects related to MND. Uncovering what happens in the motor neurons ahead of TDP-43 dysfunction and aggregation would reveal early disease mechanisms and potential therapeutic targets to prevent it from happening. By improving our fundamental understanding of TDP-43 and its aggregation, this project has the potential to inform the development of many future MND treatments.
To learn more about TDP-43 take a look at our TDP-43 infographic.
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