**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** PLANT DISEASES CAUSE HUGE LOSSES TO GLOBAL AGRICULTURAL PRODUCTION. UNDERSTANDING THE MECHANISM OF RESISTANCE TO MAJOR PATHOGENS OF CROP PLANTS IS ESSENTIAL TO ENSURE FOOD SECURITY FOR THE EVER-INCREASING HUMAN POPULATION. FUSARIUM GRAMINEARUM, REGARDED AS ONE OF THE TOP 5 FUNGAL PATHOGENS OF PLANTS BY PLANT PATHOLOGISTS WORLDWIDE, IS A SERIOUS THREAT TO GLOBAL FOOD SECURITY, AND FOOD SAFETY. OVERARCHING GOAL OF THIS PROPOSAL IS TO INVESTIGATE THE MECHANISM OF PLANT RESISTANCE AGAINST NECROTROPHIC AND HEMI-BIOTROPHIC PATHOGENS, WHICH, TO DATE, IS POORLY UNDERSTOOD. USING A 'PORE-FORMING TOXIN-LIKE' (PFT) PROTEIN, THE MOLECULAR COMPONENTS OF PLANT QUANTITATIVE RESISTANCE AGAINST THIS CATEGORY OF PATHOGENS WILL BE DECIPHERED. MECHANISTIC INVESTIGATIONS ON PFT WILL BE CARRIED OUT USING ARABIDOPSIS, NICOTIANA, AND WHEAT PLANT SYSTEMS WITH THE FOLLOWING OBJECTIVES: 1. STUDY OF THE UNCONVENTIONAL TRAFFICKING OF PFT IN PLANTS: PFT IS A LEADERLESS PROTEIN WITHOUT ANY SECRETORY PEPTIDE SIGNAL, BUT IS FOUND IN THE APOPLAST. WE WILL CHARACTERIZE THE NON-TRADITIONAL TRAFFICKING PATHWAY OF PFT USING CO-LOCALIZATION WITH CELL ORGANELLES AND CHEMICALS AFFECTING CELLULAR TRAFFICKING OF PROTEINS. 2. TEMPORAL AND SPATIAL DIMENSION OF PFT-F. GRAMINEARUM INTERACTION WILL BE STUDIED BY CORRELATING THE TRANSCRIPT LEVELS WITH PROTEIN LEVELS OF PFT IN DEVELOPMENTAL STAGES OF WHEAT SPIKES: THE INFECTION COURT OF F. GRAMINEARUM. 3. INTERACTION OF PFT WITH OTHER PATHOGENS WILL BE STUDIED FOR ANALYZING THE SPECIFICITY OF RECOGNITION OF FUSARIUM SPP. WITH PFT. THE KNOWLEDGE GENERATED IN THIS PROPOSAL ON THE MECHANISM OF A BROAD-SPECTRUM RESISTANCE PROTEIN WILL FACILITATE DEVELOPMENT OF PLANT RESISTANCE AGAINST HEMI-BIOTROPHIC AND NECROTROPHIC PATHOGENS.