Objective Plant NLR-type immune receptors tend to have a narrow spectrum of pathogen recognition, which is currently limiting their value in agriculture. NLRs can recognize pathogen effectors through unconventional domains that have evolved by duplication of an effector target followed by fusion into the NLR. One NLR with an integrated domain is the rice resistance protein Pik-1, which binds an effector of the blast fungus Magnaporthe oryzae via its Heavy-Metal Associated (HMA) domain. We solved the crystal structure of the HMA domain of Pik-1 in complex with a blast fungus effector and gained an unprecedented level of detail of the molecular interactions that define pathogen recognition. This led to the overall aim of this proposal to generate a complete picture of the biophysical interactions between blast fungus effectors and HMA-containing cereal proteins to guide the retooling of the plant immune system towards resistance to blast diseases. M. oryzae is a general cereal killer that infects wheat, barley and rice, which are staple food for a majority of the world population. The central hypothesis of the proposed research is that mutations in cereal HMA-containing proteins will result in broad-spectrum resistance to blast fungi.To achieve our goal, we will pursue the following objectives:1. BIOPHYSICS. Define the biophysical properties that underpin binding of M. oryzae effectors to HMA-containing proteins of cereal crops.2. RECEPTOR ENGINEERING. Develop Pik-1 receptors that respond to a wide-spectrum of M. oryzae effectors.3. GENOME EDITING. Mutate HMA domain-containing genes in cereal genomes to confer broad-spectrum blast resistance.At the completion of this project, we will generate a thorough understanding of the biophysical properties of pathogen effector binding to cereal HMA proteins, and deliver traits and non-transgenic cultivars for breeding blast disease resistance in cereal crops. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesmicrobiologymycologynatural sciencesbiological sciencesgeneticsmutationnatural sciencesbiological sciencesgeneticsgenomesagricultural sciencesagriculture, forestry, and fisheriesagriculturegrains and oilseedscereals Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2016-ADG - ERC Advanced Grant Call for proposal ERC-2016-ADG See other projects for this call Funding Scheme ERC-ADG - Advanced Grant Host institution THE SAINSBURY LABORATORY Net EU contribution € 1 874 187,00 Address Norwich Research Park, Colney Lane NR47UH Norwich United Kingdom See on map Region East of England East Anglia Norwich and East Norfolk Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 874 187,00 Beneficiaries (2) Sort alphabetically Sort by Net EU contribution Expand all Collapse all THE SAINSBURY LABORATORY United Kingdom Net EU contribution € 1 874 187,00 Address Norwich Research Park, Colney Lane NR47UH Norwich See on map Region East of England East Anglia Norwich and East Norfolk Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 874 187,00 JOHN INNES CENTRE United Kingdom Net EU contribution € 617 706,00 Address NORWICH RESEARCH PARK COLNEY NR4 7UH Norwich See on map Region East of England East Anglia Breckland and South Norfolk Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 617 706,00