Systems modelling age-related changes in the maintenance of dermal extra-cellular matrix: mechanisms and interventions

Overall, we will measure in-vitro and model in-silico the short-term biochemical network dynamics of extra cellular matrix maintenance (ECM) in populations of young, old and senescent dermal fibroblasts. We have shown in previous work that differences in network dynamics are highly informative and provide a means to identify parts of the network that could be targeted to restore healthy function.

The work will be first carried out in 2D culture of human dermal fibroblasts then extended to a novel 3D in-vitro system which we have established and validation as a reliable surrogate for the human dermis. Intervention strategies will be explored in the computational model and subsequently tested in-vitro. The work will involve: generation of high throughput time series data; development and application of bioinformatics workflows to analyse the data and establish networks of molecular interactions governing the maintenance of ECM; building, calibration and validation of dynamic computational model(s) in vitro; use of the model(s) to identify intervention strategies to modify network behaviour; testing of molecules in-vitro that could be used in potential treatments to improve skin healthcare.