Structural biology of cedar pollen allergy

申请人描述(由申请人提供)：申请人：Terumi Midoro-Horiuti，医学博士，德克萨斯大学医学院分校儿科助理教授。Midoro博士完成了她在儿科的住院医师资格，她在日本的过敏/免疫学临床研究员职位，以及德克萨斯大学医学分校儿童健康研究中心的研究员职位。米多罗博士和她在德克萨斯大学医学分部的主管们意识到，额外的结构和分子生物学培训将有助于米多罗博士向独立研究人员的转变。赞助商：她的导师，医学博士兰德尔·戈德布鲁姆是儿科和人类生物化学与遗传学系的教授和儿童健康研究中心的主任。共同导师，沃纳·布劳恩博士。他是人类生物化学和遗传学系的教授，也是Sealy结构生物学中心的高级科学家。 职业发展计划：Midoro博士在这里提出的教育目标是通过课程学习和对过敏原识别和过敏致敏机制的调查来学习结构生物学的理论和实践。在头两年，Midoro博士将学习正式课程：生物分子的结构和功能，以及由人类生物化学和遗传学系支持的网上生物信息学工具。她将把80%的时间投入到她的培训和研究项目中。拟议的研究将检验的假设是，构象的IgE表位在结构上不同于其他同种类型识别的表位，并且至少部分地对某些蛋白质的过敏性负责。检验这一假说的具体目的是：(1)通过探测噬菌体展示多肽库来识别构象的IgE和IgG表位。(2)通过比较致敏变应原与其系统发育同源物的结构，确定线性表位和构象表位的关键元件。(3)设计模拟Jun A 1表位的表位(模拟表位)，防止变应原与IgE结合和交联。UTMB的儿童健康研究中心和赛尔德结构生物学中心融合了不同领域的专业知识，为培训Midoro博士提供了理想的环境。该项目的完成将极大地增加米多罗博士成为独立研究载体的机会。

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.