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Details of Grant 

EPSRC Reference: EP/X020088/1
Title: KinoGlu: A Chemical Strategy to illuminate CNS Biology
Principal Investigator: Farnaby, Dr W
Other Investigators:
Researcher Co-Investigators:
Project Partners:
UCL University of Dundee
Department: School of Life Sciences
Organisation: University of Dundee
Scheme: New Investigator Award
Starts: 01 July 2023 Ends: 30 June 2026 Value (£): 427,008
EPSRC Research Topic Classifications:
Biophysics Chemical Biology
EPSRC Industrial Sector Classifications:
No relevance to Underpinning Sectors
Related Grants:
Panel History:
Panel DatePanel NameOutcome
07 Dec 2022 EPSRC Physical Sciences Prioritisation Panel - December 2022 Announced
Summary on Grant Application Form
Many neurodegenerative illnesses have no effective treatments that address the cause of the disease. The chemistry currently used to treat these diseases accesses specific protein targets in the brain and typically, attempts to block them. These approaches have had a high clinical failure rate due to not working as hoped in humans. Developing new chemistry that can generate knowledge and treatment options that function differently are therefore needed.

Targeted Protein Degradation is the method I will use to address this problem. This area of research is revolutionising chemical biology and drug discovery research. Cancer has been the early benefactor, but I wish to extend this to neurodegenerative and other Central Nervous System related diseases.

Collectively, over 1 million people have Alzheimer's and Parkinson's Disease in the UK. Both diseases are progressive and have no cure. Generating chemical research tools that enable new treatment discoveries for these diseases would provide substantive societal benefit.

This project will for the first time provide a rational method for designing and discovering molecules that can glue and degrade disease-causing proteins. This strategy will address critical issues relevant to this therapeutic area such as:

- The specific protein expression patterns that may affect how Targeted Protein Degradation can be utilised to treat diseases in the brain.

- Challenges associated with treatments reaching the brain

- Selective chemical tools that can be used to robustly validate new therapeutic concepts

To deliver my project I will make a toolbox of molecules that can bind to a group of therapeutically important proteins, Protein Kinases. These chemical tools will be able to glue disease causing protein kinases to other proteins that are part of the natural cell disposal system. The disease-causing proteins will be destroyed, returning the cell to health with no damage to healthy proteins. I will study how these tools behave in neuronal cells and use the findings as starting points to discover potent and selective kinase degrader glues.

More broadly, this project will produce chemical tools and a design approach that will be useful to many scientists. They will provide knowledge about how proteins interact with each other, both in a cellular and an in vitro environment.

Key Findings
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Potential use in non-academic contexts
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Date Materialised
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Further Information:  
Organisation Website: http://www.dundee.ac.uk