**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** COTTON SUSTAINS ONE OF THE WORLD'S LARGEST INDUSTRIES (TEXTILES) AND SERVES AS A SIGNIFICANT SOURCE OF FIBER, FEED AND OIL PRODUCTS. WITH INCREASINGLY DWINDLING WATER SUPPLIES, WATER DEFICIT IS THE MAJOR ABIOTIC STRESS LIMITING COTTON PRODUCTIVITY. HOWEVER, THE GENETIC AND MOLECULAR BASIS OF COTTON DROUGHT STRESS RESPONSES REMAINS LARGELY UNKNOWN. RECENT ADVANCES IN COTTON GENOME SEQUENCING AND FUNCTIONAL GENOMICS MAKE IT POSSIBLE TO UNDERSTAND COTTON DROUGHT STRESS AT THE GENOME AND PROTEOME LEVEL AND TO LEVERAGE GENETIC RESOURCES FOR IMPROVING COTTON DROUGHT TOLERANCE BY MOLECULAR BREEDING AND GENETIC ENGINEERING. THE PROPOSED RESEARCH IS BASED ON OUR RECENT FINDINGS WHICH REVEAL A NOVEL PHOSPHORELAY CASCADE AND PROTEIN POLY(ADP-RIBOSYL)ATION (PARYLATION) IN COTTON DROUGHT STRESS. WE HAVE IDENTIFIED A KEY TRANSCRIPTION FACTOR THAT IS PHOSPHORYLATED BY AN EVOLUTIONARILY CONSERVED MITOGEN-ACTIVATED PROTEIN KINASE (MAPK) CASCADE AND PARYLATED BY POLY(ADP-RIBOSE) POLYMERASES (PARPS) IN REGULATING COTTON DROUGHT RESPONSES IN A PHYTOHORMONE ABSCISIC ACID (ABA)-INDEPENDENT MANNER. THE GOAL OF THIS APPLICATION IS TO UNDERSTAND THE MECHANISMS AND THE INTERTWINED CROSSTALK OF THESE TWO KEY POST-TRANSLATIONAL MODIFICATIONS, PROTEIN PHOSPHORYLATION AND PARYLATION, IN ORCHESTRATING COTTON DROUGHT STRESS RESPONSES, AND GENETICALLY IMPROVE COTTON DROUGHT TOLERANCE BY REWIRING THIS UNIQUE TRANSCRIPTIONAL REGULON. THE PROPOSED OBJECTIVES REPRESENT A SYSTEMS APPROACH TO DECIPHER GENETIC AND BIOCHEMICAL MECHANISMS CONTROLLING AN IMPORTANT TRAIT IN THE COMPLEX GENOME OF AN ESSENTIAL CROP AND ESTABLISH PLATFORMS TO GENERATE DROUGHT TOLERANT COTTON CULTIVARS. THE PROPOSAL IS SUBMITTED IN RESPONSE TO PHYSIOLOGY OF AGRICULTURAL PLANTS (A1152).