Project Summary/Abstract (Core B, Stanley) Tuberculosis (TB), caused by infection with Mycobacterium tuberculosis, remains a major cause of human morbidity and mortality, particularly in the developing world. The spread of antibiotic resistant strains of M. tuberculosis has increased the urgency to develop new vaccines and therapeutics to end this global pandemic. The over-arching goal of our long-standing P01 Project has been to identify the principles of innate immune recognition that are shared across diverse pathogens needed to develop innovative tools for treating and preventing infections in humans. This P01 project represents a shift from tackling basic mechanisms towards this goal by applying the collaborative insights of our group to tackle the uniquely challenging problem of vaccine development for TB. TB research is inherently difficult as it requires dedicated facilities and infrastructure, with stringent biosafety, training, and oversight requirements in order to work safely with this biosafety level 3 pathogen. Furthermore, success of the P01 requires integrated and collaborative mouse- based infection and vaccination studies which will require a high degree of standardization and oversight in training, procedures and core reagents. This Core will function to overcome these barriers by providing comprehensive, state-of-the-art research support to all four laboratories of this Program for the manipulation and study of M. tuberculosis in a reliable, integrated, and cost-efficient manner.