Cattle-farming is one of the most important agricultural activities in the EU. This project will address issues of the health and welfare of cattle and the safety of cattle products, focussing on diseases that are on the increase in European cattle population and are aware of growing concern elsewhere. Two related diseases will be targeted, bovine tuberculosis (TB) and bovine para-tuberculosis (Para-TB or Johnes disease). The objective of the project is to use a combined functional and classical genomics and system biology approaches (system genetics) to investigate host-pathogen interactions and the host immune response to mycobacterium infection. The outcome will be 1) increased knowledge of macrophage function the application of this knowledge will be to develop tests to identify infected animals, and 2) the identification of genes that regulate the response of an individual to infection: information that could be applied in selective breeding programmes. Specifically the project will use functional, comparative genomics and in silico analysis to understand the genetic control of variation in the outcomes of disease challenge to develop molecular diagnosis tools to improve disease surveillance and to assist in selective improvement of breeding of cattle to control these diseases. Hence the project will impact directly on improved animal health. Healthy livestock are more productive and so the improvements achieved will contribute to improved efficiency and profitability of animal production and competitiveness of animal production and hence the sustainability of farming systems. The work will contribute both to improved animal health and welfare and also to the improved safety of animal products and to safeguarding human health. The market requirements will be assessed in order to lead the development of project outcomes to commercially viable products to ensure that the research is appropriately and efficiently exploited.