BOVINE RESPIRATORY DISEASE (BRD) COMPLEX IS AN ECONOMICALLY IMPORTANT AND SOMETIMES FATAL DISEASE OF CATTLE, PARTICULARLY IN YOUNG CALVES AND RECENTLY WEANED CATTLE WORLDWIDE. IN BOTH THE US AND IRELAND, RESPIRATORY DISEASE IS THE MOST COMMONCAUSE OF MORTALITY IN CATTLE. IN THE US, OVER 50% OF FEEDLOT DEATHS ARE ATTRIBUTABLE TO BRD AND APPROXIMATELY 45% AND 32% OF DEATHSARE ATTRIBUTABLE TO BRD IN CALVES AGED 1 TO 5 MONTHS OLD INNORTHERN IRELAND AND REPUBLIC OF IRELAND, RESPECTIVELY. BRD CAN RESULT BY BOTH BACTERIAL AND VIRAL AGENTS, AS DISEASE INCIDENCE IS INTIMATELY ASSOCIATED WITH AN ANIMAL'S BACTERIAL (MICROBIOME) AND VIRAL (VIROME) POPULATIONS. THEREFORE, EVALUATION OF THE ANIMAL'S RESIDENT RESPIRATORY PATHOGENS INCLUDING BACTERIAL AND VIRAL PATHOGENS IN THE UPPER NASAL CAVITY MAY HELP US TO UNDERSTAND THE IMPACT OF THESE PATHOGENS ON INCIDENCE OF BRD IN CATTLE. THIS PROJECT PROPOSAL IS COMPRISED OF THREE INTER-RELATED PROJECTS, WHICH WILL EACH INVESTIGATE SPECIFIC RESEARCH OBJECTIVES AND WILL BENEFIT FROM CATTLE POPULATION RESOURCES AND THE COMPLEMENTARY EXPERTISE OF PRINCIPAL RESEARCHERS THAT ARE INTEGRAL TO THE ENTIRE PROJECT.FOR THIS PROPOSAL, WE WILL INCORPORATE MULTIPLE CATTLE POPULATIONS, CUTTING EDGE SEQUENCING TECHNOLOGY, AND SCIENTIFIC EXPERTISE. INITIALLY, PREVELENCE OF BRD WILL BE DETERMINE IN POPULATIONS OF CALVES IN THE US AND IRELAND BY EVALUATING HEALTH RECORDS OF CALVES AT BOTH LOCATIONS. BACTERIAL AND VIRAL PATHOGENS WILL THEN BE IDENTIFIED IN THE UPPER NASAL CAVITY OF THESE CALVES TO DETERMINE THE PATHOGENS ASSOCIATED WITH BRD. TO ACCOMPLISH THIS, NASAL SAMPLES WILL BE COLLECTED FROM THESE CALVES AT TIME POINTS PRIOR TO BRD DIAGNOSIS AND AT THE TIME OF BRD DIAGNOSIS. THE DNA AND RNA FROM THESE NASAL SWABS WILL BE EVALUATED THROUGH SEQUENCING TO IDENTIFY THE BACTERIAL AND VIRAL PATHOGENS THAT ARE PRESENT IN THE NASAL SWABS COLLECTED FROM CALVES. THROUGH THIS, WE WILL BE ABLE TO IDENTIFY PATHOGENS THAT ARE PRESENT IN HEALTHY CALVES ANDCALVES DIAGNOSED WITH BRD. WE WILL THEN DETERMINE HOW BACTERIAL AND VIRAL PATHOGENS CHANGE AFTER EXPERIMENTALLY INFECTING CALVES WITH KNOWN VIRUSES THAT ARE ASSOCIATED WITH BRD. NASAL SWABS WILL BE COLLECTED FROM CALVES INFECTED WITH KNOWN VIRUSES AND CONTROL CALVES THAT WILL NOT BE INFECTED. CHANGES IN BACTERIAL AND VIRAL PATHOGENS DUE TO EXPERIMENTAL INFECTION WILL BE DETERMINED BY SEQUENCING THE DNA AND RNA FROM THE NASAL SWABS.OVERALL, THE NOVEL METHODS AND APPROACHES EMPLOYED IN THE PROJECT WILL BE OF VALUE TO NATIONAL AND INTERNATIONAL RESEARCHERS STUDYING A WIDE RANGE OF RESPIRATORY PATHOGENS INFECTING CATTLE. OUTCOMES OF THE PROJECT WILL INCLUDE: 1) A DECREASE IN ANIMAL AND PRODUCTION LOSSES DUE TO BRD, 2) IMPROVED DIAGNOSTICS FOR THE MANAGEMENT OF BRD, 3) A REDUCTION IN DRUG USE FOR BRD, 4) IMPROVED ANIMAL WELFARE, AND 5) ENHANCED AGRICULTURE COMPETITIVENESS. THUS, THE RESEARCH PROGRAM OUTLINED IN THIS PROPOSAL WILL OPTIMIZE OUR RESEARCH CAPACITY AND CAPABILITIES IN THE AREASOF ANIMAL HEALTH.