Human activities and environmental change are redistributing species at an unprecedented rate, and new host-pathogen combinations have become a major threat to humans, crops, and natural ecosystems. Therefore, the factors affecting disease transmission upon introduction of a foreign pathogen are critically important to improving risk assessment for disease emergence. Although variation among host individuals in disease resistance is regarded as a key factor in epidemiological dynamics within species, the role of standing variation in resistance has received little consideration in the context of newly introduced disease. In fact, plant and animal species show substantial resistance variation to pathogens that a species does not normally encounter in nature. One also finds that resistance mechanism can often have correlated outcomes, either positively or negatively, across different pathogen types. These results suggest that resistance mechanisms to endemic diseases exhibit properties that may underlie the important variation in responses to foreign pathogens and therefore the likelihood of their establishment. Initial results with a tractable plant-fungus model support this possibility, and this project will undertake a combination of field and greenhouse work, together with the development of theory, to build a predictive framework for the likelihood of new disease transmission into a population varying in resistance to its endemic pathogens. Intellectual Merit: The proposed investigations, involving two PIs, and a collaborating team on theory and field studies, will break new ground in the area of disease transmission related to the mounting global threats from increasingly frequent pathogen and host introductions. The project aims to reveal fundamental principles for disease spread in new host-pathogen combinations that may stem from correlated variation in disease resistance to different pathogens. Furthermore, the studies can be extended to improve predictions on the interactions of multiple endemic diseases and of eco-evolutionary feedbacks in host-pathogen systems. The work has strong implications to the closely allied field of pathogen diversification and whether fundamentally different genetic processes underlie a host's ability to resist a broad vs. a narrow range of pathogens. The role of resistance variation to introduced pathogens is central to understanding the diversity of host-pathogen affinities observed in nature, and central to developing better understanding of risks from emerging diseases in human, agricultural and wild populations.