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Genetic Mechanisms Driving Evolution of Rickettsiaceae

驱动立克次体科进化的遗传机制

基本信息

批准号：
7249972
负责人：
ANUP MADAN
金额：
$ 16.62万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-01-15 至 2007-06-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The overall goal of the proposed research is to significantly enhance our present understanding of the properties of rickettsiae, a group of obligately intracellular, arthropod transmitted, bacteria which cause at least eleven human diseases in different parts of the world. Orientia tsutsugamushi, Rickettsia akari, R. canada, and R. bellii will be studied. The complete genome sequences of these organisms will be determined to 99.99% accuracy and analyzed by computer to identify the putative RNA, protein encoding genes, pseudogenes, repeat elements, 'selfish DNA', and regulatory elements present in each organism. This information will be provided in publicly accessible databases. Unique and conserved genetic elements found in each rickettsia will be compared to help understand the mechanisms underlying evolution of their pathogenic adaptations. This initial in silico analysis requires biochemical confirmation as it depends upon the similarity of rickettsial gene sequences to well-characterized genetic elements found in other bacteria. Less than 15 of the 1000-2000 genes expected to be present in each of these species have been studied previously. Because of the intracellular lifestyle of rickettsiae and the lack of genetic systems, conventional approaches to characterization of the functional properties of these genes in rickettsiae are limited. Bacterial artificial chromosome (BAC) libraries and DNA arrays containing each gene will be constructed for each rickettsial genome. The BACs and DNA arrays will be used to characterize the expression and regulation of rickettsial genes. Selected rickettsial proteins that may be useful in vaccine development and as potential therapeutic targets will be cloned and expressed to facilitate their characterization.

描述（由申请人提供）：拟议研究的总体目标是显着增强我们目前对立克次体特性的理解，立克次体是一组专性细胞内节肢动物传播的细菌，在世界不同地区引起至少十一种人类疾病。将研究恙虫病东方体、明立克次体、加拿大立克次体和贝利立克次体。这些生物体的完整基因组序列将被确定为 99.99% 的准确度，并通过计算机进行分析，以识别每个生物体中存在的推定 RNA、蛋白质编码基因、假基因、重复元件、“自私 DNA”和调控元件。该信息将在可公开访问的数据库中提供。将比较每种立克次体中发现的独特且保守的遗传元件，以帮助了解其致病适应进化的机制。这种最初的计算机分析需要生化确认，因为它取决于立克次体基因序列与其他细菌中发现的明确遗传元件的相似性。预计这些物种中存在的 1000-2000 个基因中，只有不到 15 个之前被研究过。由于立克次体的细胞内生活方式和遗传系统的缺乏，表征立克次体中这些基因的功能特性的常规方法是有限的。将为每个立克次体基因组构建包含每个基因的细菌人工染色体（BAC）文库和DNA阵列。 BAC 和 DNA 阵列将用于表征立克次体基因的表达和调控。将克隆和表达可能用于疫苗开发和作为潜在治疗靶标的选定立克次体蛋白，以促进其表征。