Mucus plugs in asthma and other Type-2 diseases are clinically recognized as a pervasive and serious problem in disease. These tenacious plugs persist in the lungs of patients for years, in some cases causing death, yet there is still no available therapeutic capable of efficiently alleviating this feature of asthma. The lack of treatments reflects our lack of understanding of mucus plugs, driven by the shortage of suitable models in which to study airway obstruction. In order to investigate the immunological and molecular mechanisms underlying mucus plugs and airway obstruction in asthma, I will develop a novel system, in which synthetic mucus can be administered to mice. This will act as a powerful platform in which I can precisely control the contents of the airway obstruction, allowing me to introduce features of pathogenic mucus, such as Charcot-Leyden crystals (CLCs). CLCs can drive multiple features of inflammation and mucus production in asthma, but their interactions with epithelial and immune cells has not yet been fully delineated. This system will provide a model for state-of-the-art spatial analysis, revealing important information about molecular interactions that occur within a plugged airway, and how these can perpetuate inflammation. This will then lead to new avenues of treatments, which can benefit millions of asthma patients suffering worldwide.