ROLE OF DUFFY GLYCOPROTEIN IN MURINE MALARIA INFECTIONS

达菲糖蛋白在鼠疟疾感染中的作用

• 批准号: 6532621
• 负责人: CHRISTINE S OLVER
• 金额: $ 11.73万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6532621
• 关键词: Plasmodium; Plasmodium berghei; disease /disorder model; erythrocyte membrane; flow cytometry; genetic polymorphism; genetic strain; glycoproteins; host organism interaction; laboratory mouse; malaria; membrane permeability; receptor binding

DESCRIPTION (adapted from application abstract): This award would support four years of research in a murine malaria system, in which the investigator would study the invasion of malaria parasite into erythrocytes (RBC), the most critical step in malaria pathogenesis. The short term goal of the investigator is to, under the tutelage of experts in malaria, cellular biochemistry and molecular biology, test the hypothesis that the murine Duffy glycoprotein is a receptor for the invasion of Plasmodium yoelii into RBC. Development of the most current technical skills, innovative thinking, and experience in the fields of erythrocyte receptors, structural proteins and malariology are also part of this goal. The long term goal is to build an independent research program, involving the study of the host cell: parasite relationships critical in the pathogenesis of malaria. A program such as this, combined with the applicant`s expertise in veterinary clinical pathology, will provide for the basic research training of veterinary pathologists, an area of critical need in colleges of veterinary medicine. The career development of the candidate will occur in an excellent intellectual environment associated with immunologists, parasitologists, molecular biologists, and a cellular biochemist. In the years of funding of this award, the investigator will audit courses, will spend time in the laboratory working independently under the guidance of three mentors, an advisory committee and a collaborator, and will also spend time in the laboratories of other more experienced researchers (John H. Adams, mentor, and James Bamburg, advisory committee). The clarification of the role of the Duffy glycoproteins in murine malaria infections, including its parasite ligand, will open avenues of investigation into prevention (vaccines) and/or reduction in morbidity and mortality, using a convenient, relatively inexpensive, and well-developed model of human malaria (the mouse model). The first specific aim will be to confirm that the Duffy glycoprotein is a necessary receptor for P. yoelii. The second specific aim will be to identify a P. yoelii protein that is the parasite ligand for Duffy. The third specific aim will determine whether small polymorphisms in the Duffy molecule are responsible for marked differences in P. yoelii susceptibility, as is seen in a congenic mouse model. The data generated from this proposal will be used to publish three manuscripts, and will form the basis for an R01 to be submitted in the third or fourth year of funding.

描述（根据应用程序摘要改编）：该奖项将支持四个 在调查人员将在鼠类疟疾系统中进行的多年研究 研究疟疾寄生虫入侵红细胞（RBC）的侵袭，最多 疟疾发病机理的关键步骤。调查员的短期目标 在疟疾专家的指导下，细胞生物化学和 分子生物学，检验鼠duffy糖蛋白是一种假设 将疟原虫进入RBC的受体。开发 大多数当前的技术技能，创新思维和经验 红细胞受体，结构蛋白和疟疾学领域也是 这个目标的一部分。长期目标是建立独立研究 程序，涉及宿主细胞的研究：寄生虫关系至关重要 在疟疾的发病机理中。这样的程序，结合了 申请人在兽医临床病理学方面的专业知识将提供 兽医病理学家的基础研究培训，这是一个急需的领域 在兽医学院。候选人的职业发展 将发生在与之相关的智力环境中 免疫学家，寄生虫学家，分子生物学家和细胞 生化主义者。在该奖项的资金几年中，调查员将审核 课程，将在实验室中度过一段时间 三位导师，咨询委员会和合作者的指导，将 还要在其他经验丰富的研究人员的实验室里度过一段时间 （导师约翰·H·亚当斯（John H. Adams）和咨询委员会James Bamburg）。这 阐明达菲糖蛋白在鼠疟疾中的作用 感染，包括其寄生虫配体，将开放调查途径 进入预防（疫苗）和/或使用发病率和死亡率降低 人类的便捷，相对便宜且发达的模型 疟疾（鼠标模型）。第一个具体目的是确认 达菲糖蛋白是P. yoelii的必要受体。第二个特定 目的是识别P. yoelii蛋白，该蛋白是寄生虫的配体 达菲。第三个特定目的将确定小多态性是否存在 Duffy分子负责明显的P. yoelii 敏感性，如先天小鼠模型所示。从 该建议将用于发布三个手稿，并将形成 在资金的第三年或第四年提交R01的基础。