Summary This COBRE Phase 2 application proposes continued support of the UND Center for Excellence in Host- Pathogen interaction (HPI). The long-term goal of this center is to develop a deeper understanding of host responses to viral, bacterial and parasitic insults leading to acute and chronic inflammatory diseases. The vision of this Center is to continue to inspire interest in the study of host-microbe interaction and perform paradigm- shifting science that supports the notion that disease development is an interplay of the interaction between a susceptible host, foreign insult and conducive microenvironment. In Phase 1 this center made significant progress by expanding the number of investigators studying various aspects of infectious and inflammatory diseases (from the initial group of 9 labs to now 18 labs). Since the funding of Phase 1 in 2016, this core group of COBRE investigators has made significant contributions to the field by producing 169 publications, $23,617,386 in extramural funding, and 74 speaking engagements (local, national and international). With the project leader graduation success rate of 80% (4 out 6 investigators graduated with R01 funding) in Phase 1, this Center will continue to promote research on host-microbe interaction by: 1) bringing together four young investigators working cohesively in an integrative, collaborative, and multidisciplinary manner on research encompassing extremely timely COVID-19 infection, intestinal dysbiosis in food allergy, gastrointestinal parasitic infection, and viral interaction with respiratory epithelium; 2) enhance the innovative research capabilities of the Center by supporting 3 existing Phase 1 Core facilities; 3) establishing a new Computational Data Analysis Core to meet the emerging requirements of COBRE investigators; and 4) attract new investigators to the group by supporting pilot grant mechanisms. The ultimate goal is to transition the HPI COBRE to a sustainable, well- organized academic center which will serve as a conduit for increased interaction between investigators from diverse backgrounds with a thematic interest in pursuing research on various aspects of host-microbe interactions.