Project Abstract The long-term objective of this study is to enable innovative and impactful research in the fields of infectious diseases, microbiology, and global health through pathogen genome sequencing and analysis. Founded in large part to respond to the global COVID-19 pandemic, the Center for Pathogen Genomics and Microbial Evolution (CPGME) was established by the Northwestern University Feinberg School of Medicine to advance understanding, utilization, and innovation in pathogen genomics in research, clinical practice, and public health. High-throughput screening of microbial pathogens including viruses, bacteria, and fungi is critical to understanding mechanisms of pathogenicity, tracking transmissions, and performing high resolution infection surveillance. To best accomplish high-throughput genomic sequencing of microbial pathogens, we propose to purchase an Illumina MiSeq next generation sequencing system for use by the CPGME, its member researchers, and others in the Northwestern University community performing microbial genomics research. The MiSeq System is the ideal instrument for performing pathogen genomics research owing to its cost-effective scale for very small genomes, its longest read lengths among Illumina platform instruments to improve accuracy in microbial genome alignments and assemblies, its flexibility in sequencing applications, and its accessibility and ease-of-use for a large user base. This spectrum of features is unique to the MiSeq instrument and its NIH- supported users at Northwestern will be making heavy use of the instrument to investigate viral transmission, intra-host variability, bacterial colonization and pathogenesis, and mechanisms of antimicrobial resistance, among other studies. The MiSeq System will be the key to advancing microbial genomics at Northwestern, will drive the growth of the CPGME, and is a critical component supporting current and future NIH-funded research into detection, treatment, and prevention of infectious diseases.