In vivo and in silico study of altered airway smooth muscle and extracellular matrix structure and function in the remodelled asthmatic airway

Asthma is a lung disease characterised by inflammation, airway hyper-responsiveness (increased propensity to constrict when stimulated) and airway remodelling (structural changes within the airway wall). In asthma, recurrent inflammation and bronchoconstriction lead to increases in airway smooth muscle mass, altered extra-cellular matrix structure and worsening symptoms. Although remodelling is associated with poor outcomes and asthma deaths it is unclear how the processes relate to whole airway structure and function.

This project aims to uncover key mechanisms underlying remodelling and hyper-responsiveness in asthma and thereby identify potential new therapeutic targets. This will be achieved by developing multiscale mathematical models of airway function and remodelling. Models will be based upon detailed anatomical and functional data, including changes in airway microstructure (assessed using novel imaging technologies at the Harwell Research Complex) and consequent function of the airway constituents using state-of-the-art mechanical measurements of the intact airway.
This studentship will provide an excellent opportunity to work in an established group at the interface of mathematics, biology and medicine supported by a current MRC-funded project. Training in mathematical/computational modelling, advanced in-vivo skills and imaging will be provided.