This meeting highlighted the substantial progress that pulmonary scientists have made over the past decade in systematically evaluating the genetic bases for lung disease, in the expression patterns of mRNA and noncoding RNAs in lung development and disease, and in developing the tools to evaluate protein expression in lung cancer, normal and diseased lung tissue, and bronchoalveolar lavage fluid. This rapidly expanding database has already provided reductionist pulmonary biologists with a number of novel mechanistic insights that would have been inconceivable in the absence of these new approaches. Many of these insights have already led to the identification and partial validation of new targets for the treatment of currently untreatable or difficult-to-treat diseases, such as pulmonary fibrosis, acute lung injury, pulmonary hypertension, and lung cancer.
The past decade has also produced stunning achievements in refining a physical systems biology of the lung, perhaps best exemplified by a new detailed model of the steps regulating lung branching morphogenesis. The next decade will very likely see even more rapid progress in developing a molecular atlas of lung development and disease, including new insights into the roles of epigenetics and of noncoding RNAs as master regulators of disease-related programs. We can also expect comprehensive data about protein splicing, post-translational modification, protein structure, and protein–protein interactions in lung biology and disease.
The challenge of the next decade will be to extend this excellent start toward developing more comprehensive insights into beginning to develop a true molecular systems biology of the lung. In addition to identifying all of the component parts, we will need to know more about the structure of each component, how the components are physically connected (physical networks), and how they act on one another (functional networks). We will also need to develop methods to determine the precise quantitative relationships among components and how the components and their interactions change in real time. Such progress will depend on the continued use of reductionist approaches to accurately determine the actual interactions between components and how they differ with cell type, differentiation state, and local microenvironments. Thus progress in pulmonary biology in the “omics era” will continue to depend on synergistic and iterative interactions between systems thinking and reductionist experimentation, requiring all of us to think globally and act locally.