Chitin is one of the most abundant biomolecules on the planet, found in the cell wall of fungi and
bacteria and the exoskeleton of crustaceans, insects and mites. To produce their cell walls and
exoskeleton, these lower organisms use chitinases and chitinase-like molecules (CLPs) to lay down,
remodel and break-down chitin structures. Mammals do not form chitin structures, yet chitinases
and CLPs are abundantly induced in the lungs of mice and humans with asthma and in tissues
infested with parasites. This suggests that induction of these molecules is a normal part of a type 2
immune response that is protective in helminth infection, yet potentially detrimental in allergies and
asthma. Over the last year, we have created unique transgenic mouse models that will allow us to
test the role of the two most abundant chitinases (acid mammalian chitinase and chitotriosidase)
and two most abundant chitinase like proteins (Ym1 and Ym2) in models of house dust mite and
Alternaria alternata induced asthma. These allergens both contain chitin, making our models highly
relevant. We will also test how chitinases and CLPs affect lung development in early life and
remodeling in disease. Finally the potential therapeutic implications of blocking chitinases and/or
chitinase like proteins using antagonists and antibodies will be tested in various models of asthma.