Project Summary/Abstract In the past few decades, the fields of microbiology and immunology have undergone a renaissance, driven in part by technological advances establishing that the human microbiome can play a role in a number of fundamental aspects of human health and disease, in many instances through the interface with host innate immunity. The immune system functions to restrict the potential for damage caused by the microbiota while simultaneously minimizing destructive inflammatory responses. Disruption of the intensity, duration or physical location of inflammation, however, can contribute to disease. Advances in our understanding of the microbiome, and its regulation by environmental factors, along with a realization that inflammatory processes are at the core of a number of common diseases, necessitates a cross-disciplinary perspective that accommodates the host- microbe interaction in toto. The major goal of this Phase 2 Cobre is to continue to develop and expand our thematic multidisciplinary research center for the study of the interface between the microbiome, inflammation and pathogenicity within a framework to develop the careers of junior investigators. We have assembled a team of junior investigators with complementary expertise and outstanding potential, and have partnered these project leaders with well-qualified and dedicated mentors. An integrated set of projects will make novel connections between inflammatory processes and bacterial pathogenicity, and establish the basis for the development of novel therapeutics and delivery methods. We will create a multidisciplinary program in research, training, mentoring and career development that will facilitate and accelerate the transition of junior faculty to independent extramural funded status. Research will be support by a Functional Microbiomics Core that will provide germ free animal facilities, anaerobic culture capability, microbiome sequencing and bioinformatics, assay of inflammatory markers, along with whole animal imaging and intravital microscopy. An Administrative Core will co-ordinate activities and provide additional biostatistical support, along with a Pilot Project program to ensure a pipeline of investigators. Institutional commitment through a university funded Center will ensure sustainability of the thematic research program.

Project Narrative The University of Louisville COBRE in Functional Microbiomics, Inflammation and Pathogenicity is a unique thematic research center. COBRE scientists comprise a multidisciplinary group of senior mentors and junior investigators on a pathway to independence, who are focusing on diseases that involve complex interactions between microbial challenge and host inflammatory responses. Outcomes of this research may lead to the development of novel therapeutic agents and delivery systems to protect against a number of chronic and difficult to treat conditions.