** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** FIGHTBLIGHT IS AN INNOVATIVE AND GOAL-ORIENTED PROJECT AIMED AT COMBATING POTATO LATE BLIGHT, THE MOST FORMIDABLE CHALLENGE TO GLOBAL POTATO PRODUCTION. OUR GOAL IS TO INTRODUCE NEW TRAITS FOR DISEASE RESISTANCE THAT WOULD REVOLUTIONIZE HOW WE PROTECT POTATOES FROM THISDEVASTATING DISEASE.THE PROJECT HAS THREE MAIN OBJECTIVES:1. BIOENGINEERING: DEVELOP SOLANACEOUS IMMUNE DECOY RECEPTORS(NLR-ID) SCAFFOLDS TO COMBAT THE HIGHLY VIRULENT STRAINS OF THE POTATO LATE BLIGHT PATHOGEN PHYTOPHTHORA INFESTANS FOUND IN THE FIELD. SOPHIEN KAMOUN LEADS THIS WORK PACKAGE AT THE SAINSBURY LABORATORY(TSL) IN THE UK.2. CISGENICS: UTILIZE EXONUCLEASE-ENDONUCLEASE FUSIONS FOR PRECISE GENETIC ENGINEERING, INCLUDING TARGETED INSERTIONS AND REPLACEMENTS OF CONVENTIONAL INTEGRATED DOMAINS/DECOYS (IDS) WITH INNOVATIVE IDS.THIS PROCESS WILL DELIVER ENGINEERED NLR-IDS CREATED IN OBJECTIVE 1 THROUGH A CISGENIC APPROACH, OVERSEEN BY ALAIN TISSIER AT THE LEIBNIZ INSTITUTE IN GERMANY.3. PATHOLOGY: TEST CISGENIC POTATO VARIETIES EQUIPPED WITH THE NEWLY ENGINEERED NLR-ID RECEPTORS FOR DURABLE RESISTANCE IN BOTH CONTROLLED ENVIRONMENTS AND FIELD TRIALS AGAINST EPIDEMIC STRAINS OF PHYTOPHTHORAINFESTANS. THIS ACTIVITY WILL BE LED BY SILVIA RESTREPO AT THE BOYCE THOMPSON INSTITUTE IN THE US.OUR CENTRAL HYPOTHESIS IS THAT BY ENGINEERING NLR-ID SCAFFOLDS TO INCLUDE EFFECTOR TARGETS OF P. INFESTANS, WE CAN ACTIVATE SPECIFIC IMMUNE RECEPTORS AND ACHIEVE DISEASE RESISTANCE. THIS PROPOSAL BUILDS ON PRIOR RESEARCH DEMONSTRATING THE POTENTIAL FOR SHUFFLING NLR-ID WITH UNCONVENTIONAL EFFECTOR TARGETS, PLANT-DERIVED DOMAINS, AND ANTIBODIES, INTRODUCING UNPRECEDENTED FUNCTIONALITIES INTO THE PLANT IMMUNE SYSTEM.THE TIMING FOR FIGHTBLIGHT COULD NOT BE BETTER. ADVANCES IN GENE-EDITING TECHNOLOGY NOW PERMIT EFFICIENT, SCAR-FREE TARGETED INSERTIONS AND GENETIC MODIFICATIONS OVER EXTENSIVE SEQUENCES. BY THE END OF THIS GRANT, WE WILL HAVE DEVELOPED NOVEL CISGENIC TRAITS AND GATHERED FIELD DATA DEMONSTRATING ROBUST RESISTANCE TO P. INFESTANS.FIGHTBLIGHT ALIGNS PERFECTLY WITH THE RESEARCH THEME OF PROGRAMMABLE PLANTS, AS WE SEEK TO BIOENGINEER POTATOES WITH NEW CHARACTERISTICS THAT ENABLE THEM TO WITHSTAND BLIGHT. THIS PROJECT STANDS AS A PIONEERING EXAMPLE OF HOW GENE EDITING (GE) AND CISGENIC APPROACHES CAN OFFER SOLUTIONS TO CROP DISEASES, POTENTIALLY SETTING A NEW STANDARD FOR AGRICULTURAL BIOTECHNOLOGY.