CORE 5 - GENOME EDITING CORE: ABSTRACT Investigating mechanisms that underlie diabetes and its complications requires relevant experimental models. In recent years, induced pluripotent stem (iPS) cells have provided a unique means to study disease-relevant molecular pathways in patient-specific cells. The development of genome editing tools such as the CRISPR- Cas9 system has made it possible to accurately engineer cells and further refine disease modeling using iPS cells. Studies of iPS-derived cells are invaluable to the modeling of human cellular defects. However, cell- based experiments do not adequately reflect systemic changes associated with diabetes. Animal models are equally important and necessary to complement in vitro experimentation. Genome editing techniques have also made it possible to very quickly and efficiently generate new diabetes-relevant mouse models to interrogate mechanisms of disease. The Genome Editing Core (GEC) will provide a platform for investigators to create novel and unique human cellular models and mouse models to study diabetes and its complications. The GEC will use state-of-the-art methodology to 1) generate patient-specific iPS cell lines, 2) edit the genome of iPS and iPS-derived cells to probe individual genes or gene variants and 3) generate custom mouse models by gene knockdown, knock-in, knock-out or replacement. In addition to providing these services, the GEC will offer advice, reagents and tools for genome editing of experimental models and offer training for the generation and manipulation of iPS cell lines. In collaboration with the newly proposed Clinical Translational Research Core, the GEC will also serve as a repository for a large collection of unique iPS cell lines derived from type 1 diabetes, type 2 diabetes and MODY patients sourced from Joslin's extensive patient population. In sum, the GEC will constitute an invaluable resource for all aspects of diabetes research by facilitating the custom generation of relevant model systems.
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