Research Project
10241580
The mission of the Gastrointestinal Biology Core (GIBC) is to advance basic science, as well as translational and discovery studies relevant to gastrointestinal (GI) disease in CF. A central service of this Core is to offer a broad spectrum of model systems, expertise in the selection of models and analytical approaches, and the introduction or development of new model systems to facilitate GI research by DartCF scientists. The GIBC has implemented a suite of models to study GI disease in CF, including paired WT and CF mouse and human 3D intestinal organoids, 2D monolayers derived from intestinal organoids, Gut-On-A-Chip systems, engineered cell lines, transformation reagents and mouse models. The human GI cell models have been developed in collaboration with the Clinical Research Translation Core (CRTC), which provided biopsy tissue samples and GI clinical bacterial isolates. The GIBC will facilitate ongoing studies of DartCF investigators, our collaborators at other CF Research Centers, and pilot studies supported by the DartCF Pilot Project Program. The Core will also assist in the onboarding or development of novel methodologies, as needed, to advance the science of Center members and Pilot Project awardees. Notable services of the GIBC include: (1) Support for GI host- microbe co-culture studies. In the first year of support the GIBC has implemented 3D organoids and 2D organoid-derived monolayers from mice and humans, leveraged its expertise in co-culture models to study interactions between these models and GI bacteria, initiated the Gut-On-A-Chip model, and characterized over 30 bacterial isolates obtained from the stool of CF and non-CF children and from endoscopic aspirates (CTRC); (2) Expertise in single cell-RNA-sequencing, other molecular techniques, and characterization of GI organoids, working with the CF Bioinformatics and Biostatistics Core (CF-BBC); (3) Support for functional studies including forskolin-induced swelling assays (FIS) of 3D GI organoids, and electrophysiological studies of 2D organoid monolayers. In the first year of support we performed FIS assays on mouse and human 3D colonoids, and Ussing chamber experiments on 2D organoid monolayers; (4) Support for studies on mouse models to study GI disease in CF; (5) Coordination with industry to develop new multi-organ therapeutics relevant to CF, and (6) Training in the use of GI microbe-host co-culture organoid models and mouse models to members of the Center as well as investigators regionally, nationally, and around the world. The GIBC launched in 2018 to meet the research needs of DartCF faculty, and to facilitate GI research at Dartmouth. This Core is co-directed by Bruce Stanton, PhD, the Andrew C. Vail Professor of Microbiology and Immunology and Deborah Hogan, PhD, Professor of Microbiology and Immunology. Dr. Stanton and Dr. Hogan have complementary expertise covering CF, kidney physiology, cell and molecular biology, protein trafficking, microbiology, microbial ecology, host-pathogen and polymicrobial interactions, animal research, and cell culture, which has fostered the development of the central capabilities of this Core.
