Cloning Kawasaki Disease-specific antigens

描述（由申请人提供） 作为一名医生科学家，我的长期目标是确定病因， 川崎病（KD）的发病机制。 在过去的几年里， 通过K08奖保护研究培训时间，这将是 截至2000年8月完成。 这笔资金使我能够发展成为一名 医生科学家和获得实验数据，导致我最近 成功获得R01融资。 为了保证研究的时间， 需要通过K02提供额外的工资支持。 新数据显示 KD的IgA反应是寡克隆的，这导致了目标1的扩展， 我的R01基金 我的假设是， KD血管组织中寡克隆IgA应答将用于 鉴定在KD发病中重要的抗原。 这项建议会 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用途 KD中重要的抗原-抗体相互作用。 我计划：1）生成 合成抗体并确定它们是否识别KD组织中的抗原， 2)筛选KD组织cDNA文库克隆KD特异性抗原 合成抗体，以及3）确定抗原是否一致地 在KD患者中鉴定，但在对照患者中未鉴定。 重要的初步数据 证明一种合成抗体与KD结合，但不与对照组织结合 证明了这种方法鉴定抗原的可行性， KD发病机制。 作为独立调查员的一部分，我 将有机会与该部的成员进行互动， 微生物学和免疫学在西北，跨部门 免疫生物学中心，儿童纪念医院中心的研究人员 为川崎病和血管生物学研究人员在部门 儿科和病理学。 这些互动将采取研讨会的形式 系列、期刊俱乐部、实验室会议和非正式讨论。 还有， 申请书中概述了道德操守课程。 这些计划将提供 我有机会通过收购新的职业发展， 研究技能，并将通过强大的跨学科研究来培养 西北的环境

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.