The UNC CFRTCC has set as its long-term goal the systemic cure of the cystic fibrosis (CF) phenotype. There is a broad need on the UNC-CH campus for a Core Research Center to synergize and accelerate the pace of therapeutics development for CF. Our CF research base is broad and encompasses groups with expertise in CFTR biogenesis/ion transport, gene therapy, epithelial cell biology, mucus/mucin biochemistry and biophysics, microbiology/immunology, pulmonary transplant, and clinical research. This group of investigators with CF therapeutic interests includes presently > 60 faculty. To accelerate therapeutics development on the UNC-CH campus, there are needs for accurate and efficient in vivo and in vitro preclinical evaluation of therapeutic agents, access to diverse and sufficient supplies of epithelial cells (Respiratory, GI), access to new mucus/mucin technologies relevant to CF pathogenesis, and a clinical research network that provides patient specimens, clinical testing, and advisory services necessary for the therapeutics development process. In response to these needs, we have proposed a CF RTCC with four service cores that intend to provide access to their reagents/technologies for UNC, national, and international investigators. The CF RTCC will service a broad spectrum of therapies, including new chemical entities (NCEs), gene transfer vectors, and gene modification approaches. The four service cores include: (1) the Preclinical Core (Martina Gentzsch, PI),which will offer state of the art in vitro measures of CFTR function in airway and GI systems, complemented by novel CFTR knock-in and ENaC mice for in vivo studies of CF molecular pathogenesis and airways disease; (2) the Cell Models Core (Scott Randell, PI),which builds on its world class experience in providing high quality primary, P1, P2, and immortalized cells, adding novel technologies utilizing the Georgetown technique and a spectrum of respiratory and GI organospheres; (3) the Mucus Biochemistry and Biophysics Core Core (Brian Button, PI), which will provide access to unparalleled new measures of the key biochemical and biophysical mucus abnormalities that relate to CF pathogenesis for therapeutics development and novel biomarker development; and (4) The Clinical Translation Core (Scott Donaldson, PI), which will provide of the requisite respiratory and GI biopsies for genotype specific studies, validate novel sputum biomarkers for drug development, generate sputum repositories, bring a spectrum of novel imaging technologies (including F19 based MRI ventilation/washout kinetics measures) into the CF field, and provide general advice to the UNC CF and outside communities to with respect to therapeutics development. These Cores will be supported by an Administrative Core (Core A- R. Boucher, PI) which will oversee all budgetary, communication, and program enhancement functions. The UNC CF RTCC core is designed to provide a wide spectrum of services that are critical for CF therapeutics development in a fashion that we trust will be inclusive and helpful.