The Role of BBI36/38 in Lyme Disease Pathogenesis

描述（由申请人提供）：该提案描述了一个为期5年的培训计划，旨在提供教育经验和实验室培训，为成功的职业生涯作为一个独立的研究者在传染病的基础研究。候选人有以前的研究活动的悠久历史，本提案包括生物统计学和研究设计的正式课程，这将补充候选人以前的研究生工作。实验室工作将包括目前的能力领域，并允许进一步培训免疫组织化学，螺旋体的遗传操作和传染病的动物模型。詹姆斯卡罗尔博士，在实验蛋白质组学和分子发病机理领域的专家，将指导候选人，与该机构的高级研究人员咨询委员会密切合作。 莱姆病是美国报告的最常见的病媒传染病，在过去10年中发病率翻了一番。莱姆病的螺旋体伯氏疏螺旋体在蜱-哺乳动物感染的周期中调节其膜蛋白。我们已经观察到，在模拟哺乳动物感染的条件下，BBA 71，膜蛋白的pgf家族的成员，表达增加。我们推测BBA 71是一种在哺乳动物感染过程中表达的表面暴露的外膜蛋白，它将在B感染的蜱鼠中提供保护性免疫。burgdorferi。我们将集中在早期实验中的表达BBA 71蜱和特定组织中的小鼠模型的哺乳动物感染。我们将使用同源重组删除亲本B31菌株中的BBA 71表达，以检测哺乳动物感染中对BBA 71的绝对需求。最后，我们将评估对B感染的保护作用。通过用BBA 71进行被动和主动免疫而赋予的伯氏螺旋体。 莱姆病与全球公共卫生的相关性越来越大，病例数量不断增加，诊断通常会延迟。开发新的诊断和疫苗方法至关重要，该提案为开发这些新疗法提供了机会，同时为候选人提供了理想的研究环境。匹兹堡大学和这里提出的指导支持为基础研究的职业发展提供了很好的工具。

DESCRIPTION (provided by applicant): The proposal describes a 5-year training program designed to provide the educational experiences and laboratory training for a successful career as an independent investigator in basic research in infectious diseases. The candidate has a long history of prior research activities, and this proposal includes formal coursework in biostatistics and study design that will complement the candidate's previous graduate work. The laboratory work will encompass areas of current competency and allow further training in immunohistochemistry, genetic manipulation of spirochetes, and animal models of infectious diseases. Dr. James Carroll, an expert in the area of experimental proteomics and molecular pathogenesis, will mentor the candidate, in close cooperation with an advisory committee of senior investigators from the institution. Lyme disease is the most common vector-borne infection reported in the United States, and has doubled in incidence in the past 10 years. Borrelia burgdorferi, the spirochete agent of Lyme disease, modulates its membrane proteins in the cycle of tick-mammal infection. We have observed that BBA71, a member of the pgf family of membrane proteins, is increased in expression at conditions which mimic mammalian infection. We hypothesize that BBA71 is a surface exposed outer membrane protein expressed during mammalian infection, which will provide protective immunity in tick-mouse infection with B. burgdorferi. We will focus early experiments on the expression of BBA71 in tick and specific tissues in the murine model of mammalian infection. We will be using homologous recombination to delete expression of BBA71 in the parent B31 strain to test the absolute requirement for BBA71 in mammalian infection. Finally, we will assess the protection from infection with B. burgdorferi conferred by passive and active immunization with BBA71. Lyme disease is of increasing relevance to public health worldwide with cases numbers mounting and diagnosis typically delayed. The development of new diagnostic and vaccine approaches is crucial, and this proposal gives the opportunity to develop these new therapies while providing an ideal research environment for the candidate. The University of Pittsburgh and the mentoring support proposed here offer excellent tools for the development of a career in basic research.