THE AVERAGE MILK PRODUCTION OF US DAIRY COWS INCREASED FROM 2100 KG OF MILK PER YEAR IN 1944 TO 9200 KG IN 2007. THE HIGHER PRODUCTIVITY OF MODERN DAIRY COWS REFLECTS IN PART THEIR UNPRECEDENTED ABILITY TO SHIFT THE OPERATING MODE OF ADIPOSE TISSUE FROM LIPID DEPOSITION WHEN NON-PREGNANT AND NON-LACTATING TO MOBILIZATION NEAR THE END OF PREGNANCY AND IN EARLY LACTATION. THESE SHIFTS IN OPERATING MODE THROUGH THE PREGNANCY-LACTATION CYCLE REQUIRE ORCHESTRATION OF MULTIPLE CORE FUNCTIONS THROUGH MECHANISMS THAT REMAIN LARGELY UNKNOWN. THE GOAL OF THIS RESEARCH IS TO DETERMINE THE ROLE OF A NOVEL CLASS OF REGULATORY MOLECULES KNOWN AS MICRORNA IN COORDINATING ADIPOSE TISSUE CORE FUNCTIONS. THIS GOAL WILL BE ACHIEVED THROUGH 3 INTERCONNECTED SPECIFIC AIMS. IN AIM A, WE WILL OBTAIN THE FULL COMPLEMENT OF DYNAMICALLY REGULATED MICRORNAS PRESENT IN ADIPOSE TISSUE THROUGH THE PREGNANCY-LACTATION CYCLE OF DAIRY COWS. IN AIM B, WE WILL OVEREXPRESS DYNAMICALLY REGULATED MICRORNAS IN PRIMARY BOVINE ADIPOCYTES TO IDENTIFY THOSE EXERTING FUNCTIONALLY SIGNIFICANT EFFECTS ON CORE FUNCTIONS. IN AIM C, WE WILL IDENTIFY EXPRESSED GENES TARGETED BY FUNCTIONALLY IMPORTANT MICRORNAS THROUGH A COMBINATION OF COMPUTATION AND DIRECT EXPERIMENTAL MANIPULATION IN BOVINE ADIPOCYTES. WE EXPECT TO UNCOVER A MASTER MECHANISM CONTRIBUTING TO THE UNPRECEDENTED ABILITY OF MODERN DAIRY COWS TO ADJUST THE OPERATING MODE OF ADIPOSE TISSUE IN SUPPORT OF THE MAMMARY GLAND. THIS PROPOSAL WILL ADVANCE THE EFFICIENCY AND ECONOMIC VIABILITY OF US AGRICULTURE BY ADDRESSING THE MECHANISTIC BASIS FOR A PROCESS CONTROLLING THE EFFICIENCY OF NUTRIENT UTILIZATION IN DAIRY COWS.