TAR RNA AND REGULATING HIV1 TRANSCRIPTION

University Of Minnesota Twin Cities, Minneapolis MN

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Abstract

This research Career Award application describes a career development plan for Dr. Paul R. Bohjanen to pursue research training at Duke University Medical Center. Dr. Bohjanen graduated from the University of Michigan with an M.D., Ph.D. degree in 1993. He will complete an internal medicine residency at Duke University in June of 1997, and will stay at Duke for an infectious diseases fellowship. After completion of his fellowship, he will begin a junior faculty appointment in the Department of Medicine. Dr. Bohjanen's goal is to become an academic infectious diseases specialist and to head a basic science research laboratory. The training environment in Dr. Mariano Garcia-Blanco's laboratory in the Levine Science Research Center will provide the candidate with the facilities and the major equipment necessary to carry out the proposed research. The sponsor, Dr. Garcia-Blanco, has a strong record for training postdoctoral fellows and has demonstrated an exceptional ability to compete successfully for research funds. The broad long-term goal of the proposed research is to understand the role of the TAR RNA element in regulating HIV-1 transcription. Preliminary results demonstrate that circular TAR RNA decoys specifically inhibit the increase in HIV-1 transcription induced by the viral protein Tat. The specific aims are as follows: (1) the mechanism by which TAR decoys inhibit Tat-activated HIV-1 transcription will be characterized using purified transcription competent RNA polymerase II transcription complexes, (2) cellular proteins that interact with TAR RNA and are required for Tat-activated HIV-1 transcription will be identified and characterized using TAR affinity chromatography, and (3) the effect of circular TAR decoys on HIV-1 transcription in vivo will be characterized using a transient transfection assay. The research training will also include participation by the candidate in structured journal clubs and research conferences designed to enhance the research development of post-doctoral trainees at Duke University. The career development plan proposed in this application will give Dr. Bohjanen the necessary training and experience to establish an independent research laboratory by the end of the proposed training period.