The overarching goal of this application is to continue to develop and strengthen the Dartmouth Cystic Fibrosis Research Center (DartCF), reproducing in areas relevant to NIDDK mission our previous successful trajectory of CF-related research in airway biology and infection. The Pilot Project Program (P3) is an integral part of our strategy. In our first year of P30 funding, we have already expanded our capacity to investigate host-microbe interactions in the gut and the impact of gut dysbiosis on CF-related diabetes and overall systemic disease and health of these patients. The first reagents, publications and grant submissions are emerging from our inaugural set of pilot projects. As a reflection of the growing interest in and Core support for these research areas, our open RFA elicited 18 high-quality NIDDK-relevant proposals. From these, we have selected a new set of four P3 projects, all in areas related to GI, systemic or liver aspects of CF. Our strategy 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 P3 Program 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 through mentoring of junior faculty, including both basic and physician scientists. This is a proven strategy. In the past, our CF Foundation Research Development Program (RDP) and NIH Center for Biomedical Research Excellence (COBRE) awards leveraged $1.4M of pilot funding into $22.9M dollars of extramural grant support over the past 14 years. Note that the COBRE sunset in 2018 and that CF pilots related to pulmonary topics are supported exclusively by the RDP. 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) interdisciplinary Collaborative Basic or Translational Awards, and (3) Innovative Translational or Clinical Studies led by an MD or MD/PhD faculty investigator. All three mechanisms 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.
