The Daugherty lab will investigate how organisms can evolve resistance to infection and how pathogens can avoid or subvert those defenses. Disease-causing agents and their hosts are locked in a constant struggle for evolutionary dominance. As viruses and bacteria devise new ways to penetrate host defenses, host cells counter with methods to avoid or eliminate infections. The resulting molecular “arms races” drive innovation on both sides of the conflict, leaving characteristic evolutionary signatures in the genomes of hosts and pathogens. Using an integrated approach that combines biochemistry, genomics, evolutionary biology, and virology, we will leverage this combative relationship to discover new mechanisms of host immunity and pathogen evasion. For example, we are particularly interested in the evolution of systems that modify or degrade proteins, as our initial studies identified these as rapidly evolving hot spots of conflict between pathogenic viruses and the human immune system. These genetic differences, driven by the constant need to keep pace in escalating host-pathogen conflicts, can establish barriers that prevent pathogens from jumping from one host to another. Therefore, this work will shed light on how pathogens evolve to move between species and among different individuals in the human population, and could lead to innovative approaches for preventing or treating infectious diseases.