The Michigan Infectious Disease Genomics (MIDGE) Center

Project Summary – Overall The advent of genomic sequencing technologies has revolutionized our understanding of disease transmission, pathogen evolution, drug resistance, and virulence. Pathogens can quickly adapt to new environments and treatments, making it critical to understand the underlying genetic changes that drive this process. The proposed

Michigan Infectious Disease Genomics (MIDGE) Center will feature four projects, each focused on a group of pathogens, unified by a common theme of identifying pathogen determinants of epidemic success and by a common approach that combines genomic surveillance, functional genomics, and high-throughput phenotyping

assays. Project 1 examines the genomic determinants of epidemic success in SARS-CoV-2, RSV, and influenza viruses. Here, epidemic success is linked to the virus’s ability to transmit and spread within an immune population through mutations that either increase intrinsic transmissibility or allow for escape from neutralizing antibodies.

Project 2 investigates the impact of genetic background on the emergence and spread of carbapenem-resistant Enterobacteriales, where epidemic success is linked not only to drug resistance genes and mutations but also to the genetic background on which they arise. Project 3 will define genetic and genomic determinants of

colonization in Candida auris, an emerging fungal pathogen. The key to the epidemic success of C. auris appears to be its remarkable ability to adhere to and colonize the skin and the built environment, and this project will leverage whole genome sequencing, microbial GWAS, and functional genomic screens to identify the genetic

circuitry for this trait. Project 4 uses functional genomic approaches to understand the virulence of epidemic strains of Toxoplasma gondii, which are more common in South America and cause a distinct disease from that associated with other globally dispersed lineages. Genomic surveillance of scat from wild cats will be used to

further define the diversity of potentially epidemic, hypervirulent strains in this region. A Technical and Data Core will support the work of all four projects with staff bioinformaticians and research data analysts as well as Investigators with expertise in phylogenetics, high-throughput phenotyping assays, and analysis of complex data

sets. The Administrative Core will leverage local strengths in training and outreach and provide an infrastructure for regulatory compliance, financial reporting, and data and resource sharing. Through successful execution of this research plan, the MIDGE Center will develop genomic methods and protocols to study infectious diseases

and will advance genomics more broadly in basic and clinical research across viral, bacterial, fungal, and parasitic pathogens.