Cloning Kawasaki Disease-specific antigens

描述(由申请人提供) 作为一名内科科学家，我的长期目标是确定病因和 川崎病的发病机制。在过去的几年里，我有 通过K08奖保护研究培训时间，这将是 截至2000年8月完成。这笔赠款使我能够发展成为一名 内科科学家并获得实验数据，这导致了我最近 成功获得R01资金。为了保证受保护的研究时间， 需要通过K02提供额外的工资支持。新数据展示 KD患者的IgA反应是寡克隆的，这导致了目标1的扩展 我正在进行的R01拨款。我的假设是合成抗体源于 KD血管组织中的寡克隆IgA反应将在 识别在KD发病机制中重要的抗原。这项提议将 加强和发展我的研究计划，让我专注于 合成KD抗体的制备及其作为检测工具的应用 KD中重要的抗原-抗体相互作用。我计划：1)生成 并确定它们是否识别KD组织中的抗原， 2)通过筛选KD组织c DNA文库克隆KD特异性抗原 合成抗体，以及3)确定抗原是否一致 在KD患者中发现，但不在对照组中发现。重要的初步数据 显示一种合成抗体与KD结合，但不与对照组织结合 证明了这种方法识别重要抗原的可行性。 KD发病机制。作为我作为独立调查员发展的一部分，我 将有机会与新闻部的成员互动 西北大学微生物学与免疫学系间 儿童纪念医院中心免疫生物学中心研究员 和川崎病研究所的血管生物学研究人员 儿科和病理学。这些互动将以研讨会的形式进行 系列、期刊俱乐部、实验室会议和非正式讨论。另外， 申请表中列出了一门道德课程。这些计划将提供 通过收购新公司为我提供提升职业发展的机会 研究技能，并将通过强大的跨学科研究来培养 西北大学的环境。

DESCRIPTION (provided by applicant) My long-term goal as a physician scientist is to determine the etiology and pathogenesis of Kawasaki Disease (KD). For the past several years, I have had protected time for research training through a K08 award, which will be completed as of August 2000. This grant has allowed me to develop as a physician scientist and obtain experimental data which led to my recent success in obtaining R01 funding. To assure protected time for research, additional salary support through the K02 is needed. New data demonstrating that the IgA response in KD is oligoclonal has led to an expansion of aim 1 of my ongoing R01 grant. My hypothesis is that synthetic antibodies derived from the oligoclonal IgA response in KD vascular tissue will be useful in identifying antigens important in KD pathogenesis. This proposal will strengthen and develop my research program by allowing me to focus on the preparation of synthetic KD antibodies and their use as tools to detect important antigen-antibody interactions in KD. I plan to: 1) Generate synthetic antibodies and determine if they recognize antigens in KD tissues, 2) Clone the KD-specific antigen by screening KD tissue cDNA libraries with synthetic antibodies, and 3) Determine whether the antigen is consistently identified in KD but not control patients. Significant preliminary data demonstrating binding of one synthetic antibody to KD but not control tissues attests to the feasibility of this approach to identify antigens important in KD pathogenesis. As part of my development as an independent investigator, I will have the opportunity to interact with the members of the Department of Microbiology and Immunology at Northwestern, the Interdepartmental Immunobiology Center, investigators in the Children's Memorial Hospital Center for Kawasaki Disease, and vascular biology investigators in the Departments of Pediatrics and Pathology. These interactions will take the form of seminar series, journal clubs, laboratory meetings, and informal discussions. Also, an ethics curriculum is outlined in the application. These plans will provide me with opportunities for enhanced career development by acquisition of new research skills, and will be fostered by the strong interdisciplinary research environment at Northwestern.