Understanding the link between TDP-43 and UNC13A
Dr Matthew Keuss, Dr Jack Humphrey and Dr Ariana Gatt, University College London, Mount Sinai Hospital and University College London
Discovery Network
Validate therapeutic targets
April 2025 - May 2028
£999,250.57
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. TDP-43 is known to be dysregulated in about 97% of people living with MND. A gene called UNC13A is affected by TDP-43 dysfunction. Around 2 in 5 people carry a mutation affecting this gene, which the team found impairs its interaction with TDP-43. This mutation is associated with a shorter survival for people living with MND. In this project, the team will study the relationship between UNC13A and TDP-43 using lab-grown human motor neurons (created from stem cells). They will trigger changes in either UNC13A or TDP-43 and determine how that affects their respective functions. Using cutting-edge computational and sequencing technologies, the team will also compare cells with or without the UNC13A mutation, derived from brain tissues kindly donated by people who died from MND.
Why this research is important
Why this research is important: This project will identify the cellular and molecular pathways that are affected by the relationship between TDP-43 and UNC13A. We hope this will uncover new targets from future MND treatments. To learn more about TDP-43 and stem cells take a look at our infographics.
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