Structural biology of cedar pollen allergy

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DESCRIPTION (provided by applicant): Candidate: The applicant, Terumi Midoro-Horiuti, M.D., Ph.D., is an Assistant Professor in the Department of Pediatrics at the University of Texas Medical Branch (UTMB). Dr. Midoro completed her residency in pediatrics, her clinical fellowship in allergy/immunology in Japan, research fellowship in Child Health Research Center at the University of Texas Medical Branch. Dr. Midoro and her supervisors at the University of Texas Medical Branch realize additional training in structural and molecular biology will enhance Dr. Midoro's transition into independent investigator. Sponsor: Her mentor, Randall Goldblum, M.D. is a Professor in the Department of Pediatrics and Human Biological Chemistry and Genetics and a Director of Child Health Research Center. Co-mentor, Werner Braun, PhD. is a Professor in the Department of Human Biological Chemistry and Genetics and a Senior Scientist of the Sealy Center for Structural Biology. Career Development Plan: The educational goal Dr. Midoro proposes here is to learn the theory and practice of structural biology through course work and an investigation of the mechanisms of allergen recognition and allergic sensitization. During the first two years Dr. Midoro will take formal courses: Structure and Function of Biomolecules, and Bioinformatics tools on the Web supported by the Department of Human Biological Chemistry and Genetics. She will devote 80% of her time to her training and her research project. The hypothesis that will be tested by the proposed studies is that conformational IgE epitopes are structurally different from epitopes recognized by other isotypes and are, at least in part, responsible for the allergenicity of certain proteins. The specific aims that will test the hypothesis are to: (1) Identify conformational IgE and IgG epitopes by probing a phage display peptide library. (2) Identify critical elements of linear and conformational epitopes by comparing structures of sensitizing allergens with those of their phylogenetic homologues. (3) Design epitope mimics (mimotopes) of Jun a 1 epitopes that prevent IgE binding and cross-linking by allergens. Child Health Research Center and Searly Center for Structural Biology at the UTMB provide an ideal environment for training Dr. Midoro by incorporating expertise from diverse fields. Completion of this project should greatly enhance Dr. Midoro's chances of an independent research carrier.