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While complex microbial communities have been directly observed since the 17th century, laboratory research has mainly been driven by Koch's postulates -- focusing on the concept of "one microbe, one disease". Such approaches have allowed for the successful identification of microbial traits utilized to drive human disease. However, our understanding of microbial-driven infection has shifted rapidly across many diseases away from the “one species” approach. Rather, chronic infections, such as in cystic fibrosis are now known to be driven by the presence of complex biofilm-like microbial communities. These communities colonize the lung with subsequent environmental and evolutionary adaptation to exacerbate clinical disease. Treating specific pathogens in these communities is challenging due to consequences on other community members that may alter disease state and antimicrobial responsiveness to front-line CF drugs. Ecological networking within and among communities has begun to touch on multimodal culture-independent approaches including genomics, transcriptomics and metabolomics to discern these complex interactions but many outstanding questions still remain. In this workshop, we explore the ecology of CF airway communities towards effective therapies that may be translated from the lab to the clinic and vice-versa. We examine how interactions among bacterial, viral, and fungal communities influence both composition and function, and how they drive CF lung disease. We also survey how these high-dimensional interactions are reciprocally influenced by innate immune factors and CFTR modulators. The ability to model these complex communities has the framework to optimize current therapeutics and indicate potential novel approaches to improve the quality of life of people with CF. Originally recorded November 3, 2022.