Epigenetic modulation in a human in vitro model to prevent ageing

Co-Investigators: Nicholas Rattray, University of Strathclyde; Lorna FitzPatrick, Medicines Discovery Catapult

There is growing evidence in the literature implicating epigenetic proteins as putative regulators of the rate of age-related deterioration. This information provides a rationale for the development of novel therapeutics targeting the responsible epigenetic modulators. In our previous study, funded by UK SPINE, we used neuronal cell line to verify an epigenetic target as translationally relevant and is amenable to small molecule drug intervention. However, the model did not represent an ageing system. In this project, we will extend these findings to the ageing setting by collaborating with Dr Nicholas Rattray, an expert in bioenergetics in in vitro primary models of ageing at the University of Strathclyde. Dr Rattray will provide us with an established human fibroblast cell model and molecular protocols to assay a range of the hallmarks of ageing. Parallel mass spectrometry metabolomic and proteomic assays will also be performed at Strathclyde, providing a global signature of the impact of target inhibition on the ageing process in fibroblasts. The success of this project will validate our epigenetic modulator as a druggable target that regulates an ageing phenotype. We will engage with both the Drug Discovery Unit in Dundee and the wider MDC organization to establish a clear translational path to progress our target along the drug discovery pipeline.

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