The Jackson Laboratory Center for Precision Genetics

PROJECT SUMMARY OVERALL The goal of the JCPG is to deploy our end-to-end pipeline to build, validate and disseminate precision models of human disease, and to accelerate the development of treatments for patients through advanced preclinical testing. Our central innovation is our ability to link world-class services efficiently and seamlessly to provide the best possible model development and preclinical testing pipeline for our partners. Our team includes leadership with a track record of building resource programs, experienced scientific, program, and project management staff, and the support of an experienced Bioinformatics Core for data analysis and dissemination. We have made outstanding progress in developing our Center and executing its goals during In the current funding phase, our expanded outreach efforts resulted in a growing number of new external project nominations for a diverse range of disease areas from investigators and patient groups from around the country. We are on track to exceed our model generation and phenotyping goals, creating alleles that include highly complex alleles with significant humanization and/or conditional potential. Our preclinical testing portfolio includes a variety of diseases, organ systems, and therapeutic approaches, with phenotyping and molecular readouts tailored to the characteristics of each project; our success is reflected in two projects started at JAX that have progressed to clinical trials. Our Bioinformatics Core developed a JCPG website, nomination portal and algorithms inform our model development strategies. Dozens of precision, validated models are now available for public distribution through JAX’s well- established and supported infrastructure. These successes reflect the JCPG’s ability to work effectively with researchers, clinicians, foundations and families to identify and delineate disease modeling needs and then create new mouse models that serve their needs. Our Specific Aims for the next phase reflect our ambition to expand our impact through the translation of human disease discoveries into precise, predictive models of disease rapidly impact therapeutic development: 1) To optimize and deploy a comprehensive, scalable, and flexible pipeline for the generation and characterization of precision mouse models of human disease and to share mouse model resources through the MMRRC. 2) To develop and execute a robust outreach, project nomination, and project management infrastructure that expands and facilitates access to our Center for clinicians, researchers, and foundations. 3) To accelerate the development of novel, precision therapeutics by linking patient data with new precision animal models, executing preclinical testing of novel therapeutics with networks of collaborative partners. 4) To integrate an analysis and dissemination infrastructure that will facilitate development of next-generation predictive models, support the integration of outcomes with human disease phenotypes, and promote data sharing. 5) To integrate our Center with other JAX programs, resources, and external-facing services to build connections to JAX’s deep expertise in mouse biology while developing a scalable, financially sustainable model for access to the JCPG.