Microbial Genomics Biomedical Core

MICROBIAL GENOMICS BIOMEDICAL CORE (MGBC): PROJECT SUMMARY/ABSTRACT The mission of the Columbia University O’Brien Urology Research Center is to identify genetic factors and congenital malformations, such as vesicoureteral reflux, that predispose individuals to urinary tract infections (UTI) and to explore host-bacterial metabolic processes, such as heme pathways, that enable or prevent infection. UTI represent one of the most common infections, affecting 150 million people per year worldwide. In support of the goals of the Columbia O’Brien Urology Research Center the Microbial Genomics and Biomedical Core (MGBC) will provide high quality services for biobanking, extended bacterial culture, microbial genomics (microbiome analyses, comparative genomics), microbial genetics, consultation for study design and outreach for novel investigations into the pathogenesis of urinary tract infections. The MGBC will enable Columbia O’Brien Center investigators to have access to specialized genomic technologies and coordinated expert consultations for improved rigor and reproducibility in genomics and precision medicine. In recognition of the increasing impact of antimicrobial resistance in urinary tract infections the MGBC has established a biorepository of multi-drug resistant UTI isolates. The services and biorepository are specifically designed to meet the needs of two of the Research Projects of the Columbia O’Brien Center and Opportunity Pool Awardees and will be available to the wider urology research community. The MGBC will accomplish these goals through the following aims: 1) Expand a biorepository of multi-drug resistant UTI isolate to multiple sites across New York City, establish a urine biorepository from clinically well-defined patients with different UTI symptoms and perform extended urine culture for organism identification; 2) Provide Microbiome and metagenome analyses and Hi-C/MetaPore-C sequencing; 3) Facilitate whole genome sequencing of dominant UTI pathogenic clones to elucidate bacterial determinants of UTI symptomatology; 4) Generate bacterial mutants in multi-drug resistant clinical UTI isolates leveraging a highly efficient CRISPR-Cas system; and 6) Provide consultations and support of study design for the Research Projects. Importantly, the MGBC will serve as a national resource for members of other George M. O'Brien Cooperative Research Centers and other NIDDK Urologic Research Programs. In close collaboration with the Administrative Core the MGBC will ensure adherence to all fiscal, administrative, and resource sharing policies. The MGBC will also contribute to the goals of the Educational Enrichment and Opportunity Pool Programs through lectures, student mentorship, and guidance on experimental design related to microbial genomics for Opportunity Pool awardees. Taken together, the Columbia O’Brien U54 MGBC will enable state- of-the-art characterization of microbes in UTIs, with a focus on evolving multi-drug resistance, by providing a complementary set of tools harnessing molecular biology, genetics, and ‘omics technologies.