"Plant diseases represent a significant threat to global food security. One of the most notorious plant pathogens is the Irish potato famine organism Phytophthora infestans. P. infestans, the causal agent of potato and tomato late blight, continues to cost modern agriculture billions of euros annually. The most sustainable strategy to manage late blight is to breed broad-spectrum disease resistance into potato and tomato. However, current disease resistance breeding approaches are slow, inefficient, and have taken little advantage of emerging knowledge of pathogen mechanisms. Resistance genes have been identified, bred, and deployed in agriculture without detailed knowledge of the effectors they are sensing – a ‘blind’ approach. The overall aim of this proposal is to exploit state of the art findings on pathogen effector biology to drive the development of new approaches to breeding disease resistant crops. Our long-term objective is to generate late blight resistant crop varieties. The central hypothesis of the proposed research is that mutations in plant resistance and effector target genes can result in broad-spectrum resistance to late blight. The rationale behind this research is based on exciting preliminary data that demonstrated (i) there is a core set of effectors in P. infestans; (ii) plant proteins targeted by P. infestans effectors are important components of the immune response; and (iii) single amino acid changes in a potato resistance protein can result in expanded effector recognition. To achieve our goal, we plan to pursue the following specific objectives:1. Understand the molecular details of how three P. infestans effectors modulate plant immunity.2. Generate synthetic plant resistance genes with expanded recognition of P. infestans effectors.3. Generate synthetic plant effector targets with modified interaction with P. infestans effectors.4. Use the synthetic genes to engineer broad-spectrum late blight resistance."