BABESIA BOVIS AND B. BIGEMINA ARE PROTOZOAN PARASITES TRANSMITTED BY TICK VECTORS THAT CAUSE SIGNIFICANT ECONOMIC LOSSES. IT IS ESTIMATED THAT THESE TWO PARASITES CAUSE ANNUAL LOSSES OF MORE THAN $10 BILLION U.S. DOLLARS WORLDWIDE. CURRENTLY, THERE ARE NO EFFECTIVE VACCINES THAT CONTROL BOVINE BABESIOSIS. THE LIFE CYCLE OF BABESIA IS COMPLEX AND REQUIRES INFECTION OF MAMMALIAN AND TICK HOSTS FOR PARASITE TRANSMISSION. PARASITES UNDERGO MULTIPLE DEVELOPMENTAL STAGES THAT ARE CLOSELY COORDINATED WITH TICK LIFE CYCLE EVENTS. WITHIN THE TICK MIDGUT, BABESIA TRANSFORM INTO GAMETES. WE HAVE DEVELOPED A PROTOCOL TO INDUCE BABESIA GAMETOGENESIS IN IN VITRO CULTURE. USING SUPERNATANTS FROM INDUCED CULTURES, WE HAVE OBSERVED SPECIES SPECIFIC MIGRATION OF GAMETOCYTE SUBPOPULATIONS IN RESPONSE TO SOLUBLE CHEMOATTRACTANT FACTORS. THIS IS THE FIRST TIME THAT AN APICOMPLEXAN PROTOZOAN PARASITE GAMETE SOLUBLE CHEMOATTRACTANT FACTOR WITH SIGNALING PROPERTIES TO ATTRACT GAMETES PRIOR TO FUSION HAS BEEN OBSERVED. UNDERSTANDING HOW TO DISRUPT EXTRACELLULAR COMMUNICATION BETWEEN PARASITE GAMETES WITHIN THE TICK VECTOR WOULD PROVIDE A NOVEL TARGET FOR TRANSMISSION BLOCKING VACCINE DEVELOPMENT. DUE TO OUR ABILITY TO INDUCE GAMETOGENESIS IN IN VITRO BABESIA CULTURE, WE ARE UNIQUELY POSITIONED TO STUDY MECHANISMS OF BABESIA CHEMOATTRACTION PRIOR TO GAMETE FUSION. OVERALL HYPOTHESIS: BABESIA FEMALE GAMETES RELEASE SOLUBLE CHEMOATTRACTANT FACTORS THAT INFLUENCES THE DIRECTION OF MALE GAMETE MIGRATION CONSUMMATING IN GAMETE INTERACTION. TO TEST THE HYPOTHESIS THREE SPECIFIC AIMS WILL BE PERFORMED AS FOLLOWS: 1) DEMONSTRATE SPECIES SPECIFIC BABESIA GAMETE SOLUBLE CHEMOATTRACTANT FACTOR(S), 2) IDENTIFY SOLUBLE CHEMOATTRACTANT FACTOR(S), AND 3) CONFIRM MIGRATION RESPONSE TO SYNTHESIZED CHEMOATTRACTANT FACTOR(S).