Engineered Proteins to Reverse Chitin Buildup and Fibrotic Lung Disease
Abstracts
Initial Award Abstract |
|
Idiopathic pulmonary fibrosis is a progressive lung disease with a high mortality rate. Although there are many risk factors for pulmonary fibrosis (including tobacco use), the major driving causes are largely unknown. Our work suggests that exposure to environmental chitin, which is found in shellfish, parasitic worms, dust mites, and other insects but not in mammals, is a major contributing factor to the development and aggravation of pulmonary fibrosis. Mouse experiments show that some of these symptoms can be relieved by treatment with enzymes that degrade chitin (chitinases). Our goal is to create super-chitinases that can be used as a treatment to reduce the accumulation of chitin and the inflammation that precedes the development of fibrosis. We will use new techniques in protein engineering and single molecule microscopy to create these new enzymes. We will test the super-chitinases in animals created with human genetic factors that pre-dispose individuals for spontaneous fibrotic lung disease. This research will apply protein engineering to test the hypothesis that an entirely new class of biologic can potentially relieve the progression of interstitial lung disease by breaking the cycle of inflammation and fibrosis caused by chitin, a major environmental irritant. |
