"Asthma is an active area of respiratory research due to its impact on morbidity and mortality worldwide. The limited treatment options available to severe asthmatics represent a great challenge. Severe asthma is associated with neutrophilia but the role of neutrophils in this pathology remains poorly defined. A greater understanding of the role of neutrophil proteases will lead to the development of novel avenues for therapy.This project provides a unique opportunity to define the role of neutrophils and their proteases in directing the cellular inflammation and pulmonary remodelling in a clinically relevant model of allergen induced airway disease. I will combine established murine models of house dust mite-induced asthma and expertise in neutrophil/protease biology to address key questions on this unmet need for the first time. I will define the contribution of neutrophils to the development of pulmonary inflammation and structural changes due to HDM, to what extent are neutrophils responsible for the pulmonary protease imbalance in the allergic lung and the roles of their proteases and matrikines, and I will address how do neutrophils alter the homeostatic regulatory pathways within the lung. I will enhance my expertise gaining a comprehensive understanding and hands-on experience of in vivo models of asthma and complex downstream analysis by flow cytometry, mass spectrometry and microarrays, benefitting from the internationally renowned experience of the host groups. My current expertise in respiratory diseases coupled with a capacity to readily assimilate new knowledge and skill sets provides me with the ideal platform to address and successfully execute the project.This project will provide key tools for understanding the role of neutrophils in asthma, contributing to future studies that may identify key therapeutic targets for drug design in order to alleviate this disease worldwide, enhancing the EU’s position at the forefront of advances in this field."