Molecular analysis of tick-spirochete interactions

描述(由申请人提供)：扁虱是牛和人的重要病媒。这项拟议的项目旨在描述病原体伯氏疏螺旋体和莱姆病的病原体伯氏疏螺旋体之间的分子相互作用。在存在和不存在伯氏杆菌感染的情况下，将使用基于凝胶的差异显示技术来检测扁虱唾液腺和中肠的基因表达谱。识别出的基因(S)编码的蛋白质(S)的功能将通过基于计算机的数据挖掘进行初步推断。在针对候选重组蛋白的抗体存在的情况下，将探索这些基因产物在壁虱组织中伯氏杆菌发育过程中的功能意义。该项目的结果将提供(A)了解伯氏杆菌在壁虱载体中发育的分子机制，(B)提供在伯氏杆菌感染的背景下对该载体的分子操作的见解，以及(C)为差异表达的螺旋体和载体基因的功能提供线索。该项目的最终目标是根据载体和病原体确定阻止莱姆病传播的新靶点。这项调查还将为阐明其他硬虱传播病原体的潜在传播机制铺平道路。

DESCRIPTION (provided by the applicant): Ticks are significant vectors of disease to cattle and humans. The proposed project aims to describe the molecular interactions between the vector, Ixodes scapularis and the pathogen Borrelia burgdorferi (B. burgdorferi), the causative agent of Lyme disease. The gene expression profile of the tick salivary glands and midguts will be examined in the presence and absence of B. burgdorferi infection using a gel based differential display technique. The functions of the protein (s) encoded by the identified gene(s) will be inferred initially by computer based data mining. The functional significance of these gene products in B. burgdorferi development in the tick tissues will be explored in the presence of antibodies raised against candidate recombinant proteins. The results of this project will provide (a) an understanding of molecular mechanisms underlying the development of B. burgdorferi in the tick vector (b) provide insights into molecular manipulations of the vector in the context of B. burgdorferi infection and (c) provide clues to the function of differentially expressed spirochete and vector genes. The ultimate goal of this project is to identify novel targets based on both the vector and the pathogen for blocking transmission of Lyme disease. This investigation will also serve to pave the way for elucidation of mechanisms underlying transmission of other tick-borne pathogens.