GENOME EDITING CORE: Abstract Investigating mechanisms that underlie diabetes and its complications requires relevant experimental models. The Genome Editing Core (GEC) was established to assist investigators in generating cell and mouse models that can accelerate the development of new approaches to prevention, treatment, and ultimately a cure for diabetes. The GEC provides investigators the tools and expertise to leverage the latest CRISPR methodologies for the generation of both mouse and cellular models. The first component of this core, implemented approximately 5 years ago, is a mouse genome editing service. GEC staff assist investigators in the design and generation of custom mouse models with gene insertions, deletions and modifications of many kinds. The GEC is uniquely positioned to engineer the genome of the most relevant mouse models for diabetes, including the nonobese diabetic mouse model for type 1 diabetes and strains used in type 2 diabetes research (e.g. C57BL6 and C57BLKS). These models enable investigators to evaluate the consequences of genome edits at the systemic level in physiological conditions. The second component of this core enables powerful cell-based, genome-scale forward genetic screens through a CRISPR screening service and represents a major core evolution to meet the needs of the Joslin research base. GEC leadership brings outstanding expertise in this approach, and over the past year the core has acquired several genome-scale mouse and human CRISPR libraries and completed successful screens. In the present application, CRISPR screening services will be offered to perform genome-wide screens in the many various cell types to uncover mechanisms and identify novel targets in the pathogenesis of diabetes and its complications. In sum, the GEC provides a state-of-the art platform for DRC investigators to manipulate the genome of mouse and human cells at a small scale for specific hypothesis-driven projects and at a large scale for exploratory, hypothesis-generating research endeavors. The GEC further allows investigators to test genome edits in mouse models to explore gene function at the systemic level in physiological conditions.