PROJECT SUMMARY – CORE 3 The New England Regional Biosafety Laboratory (NERBL) was established in 2008 to: (1) ensure that research and tasks in response to pathogens of pandemic potential and other emerging infections (PPP/EI) are safely, efficiently, and rigorously accomplished; (2) serve as a regional resource for academic and industry partners engaged in activities that yield knowledge and medical countermeasures to PPP/EI; and (3) be ready to serve as directed by NIH/NIAID and their federal partners. A critical function of the NERBL includes the development and continuous improvement of specialized research functions unique to BSL3/ABSL3, particularly those focused on pathogens with human impact. At Tufts, existing expertise and knowledge bridges several areas of emphasis including bacteriology (tuberculosis [Mtb]), virology (influenza), and vector- pathogen interactions (eastern equine and Powassan encephalitis, tularemia). Building upon these fundamental capacities, the primary goal of Core 3 is to optimize and expand BSL3/ABSL3 resources and services for academic, industry and federal researchers to address both regional and national needs. Additionally, Core 3 will provide research services, training, and expertise across the larger Regional Biocontainment Laboratories network while also developing, validating and distributing standard operating procedures for conducting BSL3/ABSL3 research. To accomplish this, we will optimize core capacities for Mtb research, optimize core capacities for influenza research, enhance expertise in vector-pathogen interaction research, and grow core competencies through the larger RBL Network partnership. This work is supported by a set of team members with several key skills necessary for undertaking studies that involve Mtb, influenza, and tick-borne disease, including: 1) propagation and isolation of pathogens; 2) use of several experimental animal model system including tick challenge models; 3) application of medical countermeasure screening; 4) use of various aerobiology methodologies; 5) assessment of immunologic biomarkers/outcomes associated with infectious agents; and 6) integration of pathology and genomic data, including spatial transcriptomics/proteomics. Together, completion of these specific aims will strengthen the overall RBL collaborative with respect to collective expertise and capacities necessary for robust PPP/EI responsiveness, and provide a toolbox of resources for the larger infectious disease research community.