Chemokines and their receptors in the pathogenesis of tuberculosis

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DESCRIPTION (provided by applicant): THE CANDIDATE: Dr. Gillian Beamer, a licensed veterinarian with board-eligibility in veterinary anatomic pathology, is completing a PhD training program at The Ohio State University (OSU). This K08 MSCDA will support her accelerated transition to scientific independence. THE ENVIRONMENT: OSU's Division of Infectious Diseases and Department of Veterinary Biosciences (VBS) are large, well funded biomedical research centers with faculty, state-of-the-art core facilities and a history of effectively training clinician scientists. THE MENTORS: Dr. Joanne Turner and Dr. Larry Schlesinger are faculty members with joint appointments in the Center for Microbial Interface Biology (CMIB) and VBS. Both mentors are highly experienced in tuberculosis research and both are dedicated to the success of the candidate. THE TRAINING PLAN: The 4-year career development plan will accelerate Dr. Beamer's transition to scientific independence. Upon PhD completion and K08 award, she will be immediately eligible for job application and a highly valued candidate for staff scientist positions. The plan includes a short overlapping period for supervised PhD completion followed by the mentored projects outlined in the research plan. Mentoring will be substantially focused during the first 2 years of the award; in the last 2 years, contact will be maintained at a reduced level to facilitate scientific growth. THE PROPOSAL: Granuloma formation in the lungs is required to control M.tb growth. The mechanisms of cellular recruitment to form granulomas, however, are not fully known. Powerful chemoattractant cytokines (chemokines) and their receptors may play vital roles in granuloma formation and maintenance by orchestrating migration of T cells to sites of infection. In this proposal, we will determine the role of chemokines, immunologic consequences and mechanisms of T cell recruitment to granulomas in response to M.tb lung infection in vivo. Defining essential criteria for M.tb granuloma formation will further our understanding of the requirements for the generation of protective immunity.