Understanding TBK1 signalling
Patrick Lewis and Claudia Manzoni, Royal Veterinary College
Catalyst Award
Validate therapeutic targets
May 2024 – May 2025
£77,475.37
Summary
The genetic architecture underlying motor neuron disease (MND) is not fully understood. One protein with an unclear contribution to disease is tank binding kinase 1 (TBK1). This protein appears to have a role in the cellular waste disposal process known as "autophagy". Malfunctioning autophagy is implicated in a range of neurodegenerative diseases, and TBK1 levels are known to be reduced in MND. Dr Lewis will investigate TBK1 in greater detail by analysing how it interacts with other proteins using a computational approach. After establishing a “map” of these links, he will identify targets that could boost TBK1 activity.
Why this research is important
TBK1 is implicated in both inherited and non-inherited forms of MND. Mapping what this protein does in the brain in health and disease could provide valuable information on the cellular events underlying MND. If TBK1 deficiency proves to be a critical event in MND, restoring normal levels could be a potential therapeutic strategy and this project could open up new potential treatment avenues.
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