A window onto fish immunity: Visualisation of immune responses in Zebrafish

Background: Farmed fish provide an important source of healthy, nutritious food, and is a growth industry that now employs several thousand people and contributes significantly to the UK economy. But can we guarantee the future of farmed fish when, like many intensively reared animals, they are susceptible to infection? Vaccination is a well-established and safe method for protecting livestock (and indeed humans) from infectious disease. Effective vaccines generate an immune response that is appropriate for the pathogen and this is co-ordinated by different subsets of helper T cells. While helper cells and associated genes have been identified in fish, their function has yet to be investigated. This lack of understanding is hampering the development of fish vaccines.
Aim: We propose to study the immune system of zebrafish, to learn more about the immune system of bony fish generally. While not farmed, zebrafish can be genetically modified and transparent strains allow live imaging of cellular immune responses. The student will generate and express inducible transgene constructs which combine expression of viral proteins currently being developed as DNA vaccines with different genetically encoded adjuvants. Cellular responses will be live-imaged and responding helper T cells profiled by various analytical techniques. Responses in wild-type zebrafish will be contrasted to responses in zebrafish with mutations in genes which regulate helper T cells in other (mammalian) species. Ultimately, we hope our research and the future research it inspires will translate into the development of effective vaccines that protect economically valuable farmed fish from infectious disease.