Grant: Discovery Grants Program - Individual

Formation of the lung is an important process required for survival. Our research is focused on understanding how cells function during lung development and how this function is controlled. Cells within any tissue are surrounded by a “scaffold” of proteins called the extracellular matrix. This scaffold is not a static structure and is constantly being changed or remodelled by removing and adding different proteins. Importantly, this scaffold has the ability to signal to cells. This signalling can occur through direct interaction between the scaffold and the cells, as well as by the scaffold binding to and releasing specific signalling proteins called growth factors. My previous work found that when one of the proteins within the scaffold (called fibronectin) is altered, the formation of the lung airways is impaired because the cells within the airway do not divide (or proliferate) appropriately. Therefore, our proposed studies are focused on understanding how this entire scaffold is changed during lung development and how changes to the scaffold alters lung development. To do this, my lab will initially examine how the scaffold is changed (i.e. how proteins are deposited or removed) during formation of the airways. Lungs will be isolated from developing mice and we will look at the expression of genes associated with the scaffold and how these genes change. We will also use a new technique, called TAILS, that allows us to identify the proteins within the lung that are being changed, specifically degraded or cleaved by enzymes. Our long term goal will be to determine how changes to the scaffold change airway formation. For this, we will use a model of lung development where the scaffold appears to be changed and examine how these changes alter lung development. These studies will allow us to identify how the scaffold, and importantly, changes to the scaffold, control cell function during lung development, specifically during airway formation. Overall, our work will identify new ways through which essential cellular functions are controlled in the developing lung by the surrounding scaffold or matrix. Importantly, there is similarity with how cells are controlled in many different developing organs. Thus, in addition to identifying specific factors that control lung development, our studies will address concepts that are important for the development of many different organs.