The overarching goal of this application is to develop the Dartmouth Cystic Fibrosis Research Center (DartCF), building on our strong history of CF-related research in lung infection, inflammation/immunity, and translational science to expand our capacity to investigate host-microbe interactions in the gut and the impact of gut dysbiosis on CF-related diabetes and overall systemic health of these patients. Our ability to build the current strengths of our research base stems directly from effective use of pilot funds over the past ~15 years. Using our experience and outstanding track record of enhancing research capacity through pilot funds, the Pilot Project Program (P3) will (1) encourage development of preliminary data to open up new research opportunities, refine hypotheses, and strength proposals to compete for extramural support, (2) enhance collaborative and interdisciplinary research to engage current researchers at Dartmouth, including those with a record of CF research and those new to the field, and support newly recruited faculty, (3) deepen our reservoir of translational and clinical research projects by providing funds to physician-scientists and their collaborators, (4) nucleate the submission of multi-investigator grants, and (5) support professional development of our faculty through mentoring of junior faculty and physician scientists. Using the NIH Center for Biomedical Research Excellence (COBRE) and the CF Foundation Research Development Program mechanisms as models, we have leveraged $1.4M of pilot awards into $22.9M dollars of extramural grant support over the past 14 years via the structure proposed here. Using this model as a framework, we have designed an inclusive Request for Applications (RFA) and rigorous multi-stage review procedure to award P3 grants to expand our capabilities to investigate host-microbe interactions in the gut and the impact of gut dysbiosis on CF-related diabetes, under three mechanisms: (1) Mentored Basic or Translational Awards for junior faculty, (2) Collaborative Basic or Translational Awards for interdisciplinary studies, and (3) Translational or Clinical Studies led by an MD or MD/PhD faculty investigator. All three mechanisms will foster interdisciplinary, multi- investigator, and clinically relevant research. By engaging existing and new faculty and supporting transformative research, the P3 will directly enhance the identity, impact, and research base of DartCF.