Project Summary Avoidance is a form of host defense against pathogens that reduces the risk of initial contact between host and pathogen. Avoidance behaviors represent an animal's first line of defense against pathogens and play a primary role in determining whether and how a host-pathogen interaction will proceed. Yet avoidance has not been studied within the rich theoretical framework that has been built for other forms of defenses against pathogens, such as physiological resistance. Both avoidance and resistance reduce infection, and thus it could be argued that the extensive literature on resistance can be simply extended to predict the ecological and evolutionary dynamics of avoidance. However, avoidance may evolve differently from resistance, especially if the costs of avoidance are lower or more variable. Moreover, as the gatekeeper of the host-pathogen interaction, avoidance is likely to have downstream effects on the strength of selection on resistance. Predictions about the primary role of avoidance in determining host-pathogen interactions have proven challenging to test because avoidance and resistance are hard to separate empirically: infection outcomes are a product of both. This research addresses these knowledge gaps by combining theoretical and empirical research to generate and test predictions for the evolution of avoidance and resistance as components of a `defense cascade.' Theoretical approaches will generate predictions for the evolutionary processes that govern avoidance and its association with resistance (Aim 1). Experiments will be conducted in a tractable system in which avoidance and resistance not only can be measured separately, but also can be evolved separately: the model organism Caenorhabditis elegans and bacterial pathogen Serratia marcescens. Assays and experimental selection schemes will characterize the fitness costs and benefits of avoidance relative to resistance (Aim 2), and examine the evolution of defense modes separately and in combination (Aim 3). Together, this approach will break down the steps of the defense cascade, establishing a critical foundation for understanding the evolution of avoidance and its downstream impacts on resistance evolution. This research will use a novel approach to bridge the gap between behavioral ecology and evolutionary theory of pathogen defenses, laying a foundation to address questions relevant to public health decisions surrounding avoidance behaviors. Through the proposed research, the Trainee will develop technical skills for complex mathematical modeling and maintaining a C. elegans laboratory. The Trainee will also focus on professional skills such as mentorship and collaboration. The training will take place in the Department of Biology at the University of Virginia, under the supervision of two successful co-sponsors who will contribute diverse perspectives, and have the resources to support the Trainee. Through this fellowship, the Trainee will build on her str...