Investigation of novel protease-antiprotease imbalances associated with chronic airways disease

About the Project

Chronic obstructive pulmonary disease (COPD) is a progressive airways diseases associated with cycles of infection and inflammation, lung tissue destruction and pulmonary decline. Intensive management needs and frequency in hospitalization give rise to significant treatment costs (UK £4.7 bn & USA $42.6 bn pa). New therapies targeting some of the specific cellular processes associated with COPD could help improve both lung function and quality of life which would also reduce hospital admissions.

COPD is an umbrella terms for a range of conditions to include chronic bronchitis (inflammation) and emphysema. A protease-antiprotease imbalance associated with chronic inflammation and neutrophilic infiltration is well established in COPD. To date, however, most attention has focussed on the neutrophil serine protease, neutrophil elastase and its endogenous inhibitor, alpha1 antitrypsin (AAT), also known as serine protease inhibitor A1 (serpinA1). Indeed, a genetic deficiency of AAT is a risk factor for the development of early onset COPD giving rise to aberrant levels of elastase activity which can inflict significant damage to the aveolar tissue impairing gas exchange (emphysema).

Recent work in our lab has shown that in addition to serpinA1, a number of other serpins are expressed which can inhibit a range of physiologically relevant proteases in the airways. This project will thereore progress these studies to yield valuable insight into as yet undisclosed functions of these serpins in the airways. These serpins have the potential to be critical regulators of protease activity in the lungs, down-regulation of which would contribute the protease-antiprotease imbalance which plays a significant role in the progressive destruction of lung tissue.

These studies directly align to the strategic research interests of the Martin group and research collaborators and provide opportunity for the successful applicant to benefit from the significant expertise of the research group.

Funding Notes

This project is not funded; applications are welcome from self-funding candidates.