HUMAN GENETICS AND MICROBIOME CORE: PROJECT SUMMARY The Human Genetics and Microbiome Core will be co-directed by Mark Daly and Curtis Huttenhower. Core services range from routine and heavily used molecular biology services (e.g., whole plasmid DNA sequencing, siRNA/shRNA and CRISPR screens) to tools for data generation and analysis of genetics and the microbiome in IBD (e.g., high-throughput nucleotide extraction, gene profiling, 16S rRNA sequencing, deep shotgun sequencing, and metabolite profiling). The Core’s continuing focus on methods optimization and development provides cost-effective access to cutting-edge techniques and analysis tools, ensuring that investigators remain at the forefront of digestive disease research. For genetics studies, investigators benefit from the expansion of tools for genetic manipulation, including new CRISPR reagents, and access to emerging results and techniques from ongoing sequencing projects. The recent addition of a state-of-the-art gnotobiotic facility and a comprehensive open-access biobank of human gut bacteria will aid investigators studying the impact of the microbiome on host physiology and metabolism. The Core offers bioinformatics support for all studies, with an emphasis on development of novel computational methods and pipelines. Additionally, the IBD Data Science Commons will address growing data integration and analysis needs, serving as both a repository for multi’omic data and a space for analysis and visualizations that enable scientific discovery. Education and training services include end-to-end consultations and instruction on experimental design, data generation, and bioinformatics analysis. Operating at the intersection between patient samples and basic research techniques, the Core will be a major connection point for clinicians and basic researchers. The specific aims of the Human Genetics and Microbiome Core are divided according to its two themes. For genetics services, the Core will (1) facilitate the application of advanced experimental platforms for genetics, genomics, and high-throughput data analysis to discovery efforts relevant to IBD; (2) provide a centralized facility and personnel for performing state-of-the-art recombinant and PCR-based DNA procedures and RNA interference and provide cost-effective and high-quality molecular biology reagents and services; and (3) provide a resource for disseminating a wide range of molecular biology, genetic, and bioinformatics technologies. For microbiome services, the Core will (1) provide an end-to- end sampling and multi’omic profiling system for the host and microbiota in IBD and gastrointestinal disease; (2) provide computational resources to analyze and interpret the microbiome; and (3) develop cutting-edge solutions in microbiome research that will drive therapeutic discovery.