The immune system and the skeleton are often viewed as separate parts of our biology. However, recent research has revealed that the skeletal and immune systems interact more than previously appreciated as part of the “osteoimmune” system. Hyperinflammation experienced earlier in life, which can result in chronic inflammation, therefore affects the skeleton as well as other parts of the body. This project examines immune and inflammatory proteins in bone that are markers of this complex relationship between bone and immune function and applies them to questions about biocultural processes in human societies. The project advances knowledge in skeletal biology and bioarchaeology by combining traditional observations of skeletal pathology with proteomic analysis to better identify inflammatory responses that may be shaping human morbidity and mortality in the past and present. The broader impacts of the project include student training, including individuals from groups underrepresented in STEM; curriculum expansion; international research collaborations; and engagement with schools, communities, and the public. <br/><br/>Early life biological stress and immune system over-activation are thought to produce cascading effects involving phenotypic plasticity and life history trade-offs that shape predilections for later-life inflammatory and hyperinflammatory phenotypes. This project pursues a cross-disciplinary study of skeletal inflammatory diseases, combining observations of periodontal disease and periosteal reaction with proteomic analyses of at least of four independent inflammatory protein biomarkers (osteocalcin, macrophage inflammatory proteins, leukocyte-derived proteins, and neutrophil-derived proteins) in individuals possessing an inferred hyperinflammatory phenotype. The PIs address biocultural hypotheses about the co-occurrence of pathological processes, the role of early life environments in shaping immune response, and the influence of sociocultural dynamics on human biology.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.