Plant diseases represent one of the most important risks to ensuring global food security and new control strategies for the world’s most serious crop diseases are urgently needed. This project will lead to an unparalleled advance in understanding of the world’s most serious crop disease - rice blast. Each year rice blast disease claims 11-30% of the potential rice harvest, which is enough rice to feed 60 million people. The fungus that causes rice blast disease, Magnaporthe oryzae, is a highly adapted cereal pathogen, which forms specialized infection structures called appressoria that can breach the intact leaf surface and allow the fungus entry to living plant tissue. This project will result in the most comprehensive understanding of the biology of plant infection by a pathogenic fungus. The cross-disciplinary research programme will integrate next generation DNA sequencing, digital transcriptional profiling, and high throughput gene functional analysis, with cell biology and live cell imaging. In this way, the transcriptional networks and gene regulators of fungal virulence will be identified and characterized at a systems level. The project will investigate the nature of the host-pathogen interface using live cell imaging of stable transgenic rice lines expressing fluorescent fusion proteins that define specific sub-cellular domains and will allow the precise mechanism of cellular invasion by the fungus to be determined. The project will also use protein-protein interaction studies to identify the major effectors used by M. oryzae to suppress plant immunity and facilitate proliferation of the fungus within living plant tissue. In parallel, comparative genome analysis will define conserved the full repertoire of effector functions and the transcriptional networks necessary for plant disease. Comprehensive functional analysis of M. oryzae effectors will then be carried out by targeted gene deletion, spatial localization and target identification.