PROJECT SUMMARY – OVERALL The goal of this proposal is a coordinated, synergized, and integrated COBRE research program, called the “BioSystems Networks and Translational Research – Insights into Inflammation (BioSNTR-II),” at South Dakota State University (SDSU), Brookings, SD. Our research objective is to improve human health by advancing the understanding of molecular, cellular and tissue-level mechanisms of inflammation research via multi-disciplinary approaches. The overarching hypothesis is that intracellular regulatory events are governed by cell-cell communication across the macrophage, stromal and lymphatic axes during the inflammatory response and its resolution. Junior research project leaders, mentored by senior faculty, define the three research projects of BioSNTR-II in the areas of: macrophage cell biology in inflammation, the role or primary cilia in regulating lymphangiogenesis in inflammation and regulation of tumor necrosis factor signaling and cell death pathways. These projects will be supported by two cutting-edge research cores in (1) transcriptome sequencing, analysis and model development (Transcriptome and Network Analyses Core) and (2) CRISPR- based gene editing and Integrated Microscopy and Gene Evaluation (CRISPR-IMAGE). In addition, an Administrative Core is proposed to support the fiscal and personnel management, implementation, oversight and evaluation of both the research projects and the cores. The synergy and integration of these components has been carefully planned to maximize impact while supporting training, professional development, and the career potential of a cadre of bright, promising basic researchers. The Center will achieve success through the following aims: (1) Develop and manage a thriving environment for inflammation research at SDSU, (2) Establish new Research Cores to expand and enhance biomedical research at SDSU, and (3) Guide center performance and sustainability with assessment and advisory board input.