The purpose of this NOSI is to promote research characterizing the pathobiological processes and mechanisms that drive the onset and progression of lung diseases at a molecular/cellular level, providing a systems-level understanding by studying experimental systems with cellular heterogeneity and 3-D architecture. It is expected that projects supported by this NOSI will utilize ex vivo preparations (e.g., thin human lung slices) or 3-D multi-cellular in vitro systems (e.g., organoids) of human lung cells and will employ state-of-art multi-omics measures (e.g., spatial or single cell/nucleus omics) to better understand specific pathobiological processes in systems of interacting cell types.