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）：拟议的研究的总体目标是显着增强我们对立克西亚（Rickettsiae）的特性的当前理解，Rickettsiae是一组有强制性的细胞内，节肢动物传播的细菌，引起世界不同地区至少11种人类疾病。将研究Orientia Tsutsugamushi，Rickettsia Akari，R。Canada和R. Bellii。这些生物的完整基因组序列将确定为99.99％的准确性，并通过计算机分析，以鉴定每个生物体中存在的假定RNA，蛋白质编码基因，假基因，重复元素，“自私的DNA”和调节元件。此信息将在可公开访问的数据库中提供。将比较在每个立克中发现的独特和保守的遗传元素，以帮助了解其致病性适应的基础机制。这些初始分析中的初始分析需要生化确认，因为它取决于立克基因序列与其他细菌中发现的良好遗传元素的相似性。先前已经研究了这些物种中每种物种中预期存在的1000-2000个基因中的15个。由于立克西亚的细胞内生活方式和缺乏遗传系统，因此在立克siae中这些基因的功能特性表征的传统方法受到限制。细菌人造染色体（BAC）文库和包含每个基因的DNA阵列将为每个立克基因组构建。 BAC和DNA阵列将用于表征立克基因的表达和调节。可能在疫苗发育中有用的精选的立克蛋白，并且将克隆并表达潜在的治疗靶标，以促进其表征。