Lung Development and Disease
Group Leader : Charlotte Dean
The lung develops by a process known as branching morphogenesis from a simple bud to a complex tree-like structure comprised of several differentiated cell types that facilitate efficient gas/air exchange. This process requires extensive interactions between the lung endoderm and mesenchyme, however, relatively little is known of the molecular events required for development of a fully functional lung.
Our group is seeking to understand these molecular events with particular emphasis on the process of branching morphogenesis. Moreover it is our hypothesis that some of the genes critical to lung development will also be involved in lung disease. To identify developmentally important genes and investigate their role in lung disease pathogenesis, we use both forward and reverse genetics. Once we have identified mouse mutants with developmental lung defects, we thoroughly characterise the lung phenotype and we then use inducible models of fibrosis and allergic airway disease (asthma) to see if they are susceptible to lung disease.
We are currently studying three broad categories of mouse mutants as tools to broaden our understanding of lung disease pathobiology.
- Models with abnormal lung development- It has become apparent that a number of genes critical to lung development are dysregulated in lung disease. We therefore seek to understand more of the pathogenesis of lung disease by elucidating the molecular mechanisms of lung development. Our recent work in this area has focused on the role of the Planar polarity (PCP) pathway in lung development (see current projects for more details).
- Mouse models of candidate human asthma susceptibility genes- In collaboration with Professors Cookson and Moffatt (Imperial College, National Heart and Lung Institute) we are investigating both point mutants and null mutants of human asthma association genes in the mouse. This work will enable us to confirm the identity of asthma susceptibility genes identified in human GWAS studies and to elucidate gene function.
- Models of age-related respiratory disease– As part of the ENU ageing screen that is currently being undertaken at Harwell we are phenotyping mice for age-related susceptibility to infection and lung function deficits in order to identify novel mouse models of age-related respiratory disease. This work is in collaboration with Professors Lloyd and Hussell at Imperial College, National Heart and Lung Institute.