At some point in their life all animals will be challenged by the threat of infectious disease. How an animal copes with pathogens will depend on their ability to resist infection or to minimise the virulence of disease once a pathogen has invaded. Accordingly, understanding the mechanisms behind the defence against infection and virulence has been a major goal of not only evolutionary biologists interested in host-pathogen interactions, but also epidemiologists involved in public health considerations and agriculturalists attempting to minimise the impact of pests. However, despite the importance and widespread occurrence of host-pathogen interactions, very little is known about the genetic architecture underlying the different lines of defence that animals use to prevent infectious disease. I propose a research program that will examine the evolutionary genetic basis of host-pathogen interactions in the crustacean Daphnia magna and its bacterium pathogen Pasteuria ramosa. To do so I will take advantage of a newly developed, high coverage quantitative trail loci (QTL) panel to quantify the genomic basis of virulence in this species and the potential role that the host-immune system has in defence against infectious disease. I will also use a novel experimental evolution approach to explore the co-evolutionary link between the ability of a host to resist infection and the resulting severity of disease. This innovative blend of my expertise in evolutionary manipulations and multivariate statistics with the new challenge provided by state of the art genomic techniques, will allow for considerable advances to be made in our understanding of how host and pathogen genomes interact to influence infectious disease. Moreover, by integrating aspects of evolutionary genetics, genomics and immunology, this project will foster significant cross-disciplinary collaborations and enhance Switzerland and Europe’s reputation for integrative evolutionary research.