The Systems Ecology of the CF Lung

Much of the new knowledge that has been accomplished by the CF research community has arisen from studies of reduced preparations such as isolated cells, a single channel, a single signaling pathway, a specific bacterium. However, the airway is a complex environment, with ~20 different epithelial cell types working together in the context of oxidative burden, many invading pathogens that all of us are exposed to every day, and multiple immune system cell types charged with preserving sterility, often with added insult from cigarette smoke or other environmental exposures.

Understanding how these interactions between components of the airway take place under physiological conditions will only be achieved by studying them in a living patient, rather than relying upon reduced preparations. When the individual components of the complex CF lung are studied in isolation, the mechanisms that regulate their interactions and responses to insults are lost. We will only achieve a complete understanding of the pathogenesis of progressive lung disease in CF by studying this complex environment in situ, with all of the relevant components in place; one must consider the whole system.

We hypothesize that it is by taking such a systems view of CF disease that the CF research community will be able to achieve the next major improvements in life-expectancy for CF patients. With this sort of thinking in mind, our team will study the complex environment of the CF lung by considering each component as a member of a community, and applying the scientific principles of both systems biology and community ecology.