PROJECT SUMMARY/ABSTRACT Microbiology and metagenomics core The purpose of this core is to facilitate high-throughput characterization of the acne microbiome from clinical samples of acne patients generated from the Acne Center of Research Translation (CORT), and to advance analysis of the function of these microbes beyond basic genomic characterization. Next-generation sequencers have transformed microbiome research but have proven insufficient to understand the biologic relevance of this microbial genetic information in the skin. The acne microbiome has been partially characterized but without understanding of how products of these diverse organisms influence the pathophysiology of acne. The Core Director, Core Associate Director, and staff of this core have extensive experience in the generation and analysis of metagenomic data and have successfully developed a panel of functional screens to enable analysis of how target cells respond to the metabolic products of microbe. This requires expertise in the study of C. acnes, the predominant bacterial species in acne that is anaerobic and fastidious, thus requiring expertise for isolation and culture. C. acnes produces a range of fermentation metabolites and other products that can alter host immune responses and the growth of other organisms. This core will produce libraries of bacterial organisms from the skin, perform metagenomic analysis from skin swabs, and functionally screen libraries for their capacity to alter the immune response of fibroblasts, keratinocytes and immunocytes relevant to the skin of acne subjects, and analyze these observations to generate hypothesis for further testing. The core will also work closely with the transcriptomics core and lipidomic screens at UCLA to further integrate data for validation and discovery. This ability will transform the utility of the data to members of the CORT.