Structural biology of cedar pollen allergy

雪松花粉过敏的结构生物学

• 批准号: 6874517
• 负责人: TERUMI MIDORO-HORIUTI
• 金额: $ 12.13万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6874517
• 关键词: SDS polyacrylamide gel electrophoresis; allergens; biomimetics; chemical binding; clinical research; conformation; enzyme linked immunosorbent assay; human subject; hypersensitivity; immunoglobulin E; immunoglobulin G; peptide library; phage display; pollen; structural biology; western blottings

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.

描述（由申请人提供）：候选人：申请人Terumi Midoro-Horiuti，M.D.，哲学博士、是德克萨斯大学医学分支（UTMB）儿科系的助理教授。Midoro博士完成了儿科住院医师、日本过敏/免疫学临床研究员和德克萨斯大学医学分支儿童健康研究中心研究员的工作。Midoro博士和她在德克萨斯大学医学分支的主管意识到，在结构和分子生物学方面的额外培训将促进Midoro博士向独立研究者的过渡。赞助人：她的导师，兰德尔·戈德布卢姆，医学博士。是儿科和人类生物化学和遗传学系的教授，也是儿童健康研究中心的主任。共同导师，Werner Braun博士。是人类生物化学和遗传学系的教授，也是西利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工作和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。Midoro将参加正式课程：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络生物信息学工具。她将把80%的时间用于培训和研究项目。将通过拟议研究检验的假设是，构象IgE表位在结构上不同于其他同种型识别的表位，并且至少部分地负责某些蛋白质的变应原性。具体的目标是测试的假设是：（1）通过探测噬菌体展示肽库鉴定构象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，确定线性和构象表位的关键元件。(3)设计Jun α 1表位的表位模拟物（模拟表位），防止过敏原与IgE结合和交联。UTMB的儿童健康研究中心和Searly结构生物学中心通过整合不同领域的专业知识为Midoro博士提供了理想的培训环境。 这个项目的完成将大大提高Midoro博士成为独立研究载体的机会。