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Development of small molecule inhibitors of WRN: a model system of ageing

Reference	ERA16310
Principal Investigator / Supervisor	Professor Lynne Cox
Co-Investigators / Co-Supervisors	Professor Michael Green, Professor Declan Naughton, Dr Ana Rodriguez
Institution	University of Oxford
Department	Biochemistry
Funding type	Research
Value (£)	213,236
Status	Completed
Type	Research Grant
Start date	01/09/2003
End date	31/08/2006
Duration	36 months

Abstract

The current best model to study human ageing is Werner's syndrome. However, patient material is rare and cells present with accumulated genetic defects in addition to the original loss of functional WRN protein. We propose to overcome these problems using three complementary routes to inhibit WRN activity in normal cells. Peptide motifs that bind to functional domains of the WRN protein will be identified by phage display technology. These peptides, and stabilised chemical derivatives, will be tested directly for ability to inhibit helicase and exonuclease activities of WRN protein in vitro and in whole cells in culture. Additionally, expression of WRN in normal cells will be inhibited by dsRNAi and by the use of addicted PNAs.

Summary

unavailable

Committee	Closed Committee - Biochemistry & Cell Biology (BCB)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	Experimental Research on Ageing (ERA) [2001]
Funding Scheme	X – not Funded via a specific Funding Scheme

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