Comparative Genomics of the Chlamydiaceae

衣原体科的比较基因组学

• 批准号: 7179258
• 负责人: Garry Stewart Anthony Myers
• 金额: $ 30.17万
• 依托单位: J. CRAIG VENTER INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7179258
• 关键词: Address; American Type Culture Collection; Animals; Bacteria; Bacterial Genome; Benchmarking; Biological Warfare; Chlamydia; Chlamydiaceae; Chlamydiales; Chlamydophila pneumoniae; Chlamydophila psittaci; Closure; Communities; DNA; Data; Databases; Deposition; Development; Disease; Disease Outcome; Distant; Educational workshop; Evolution; Family; Gene Pool; Genes; Genetic; Genetic Determinism; Genome; Genomics; Geographic Locations; Horizontal Gene Transfer; Host-Parasite Relations; Human; Immune; In Vitro; Individual; International; Investigation; Koala; Laboratories; Libraries; Life; Life Style; Link; Methodology; Molecular; Names; National Institute of Allergy and Infectious Disease; Numbers; Nutritional Requirements; Open Reading Frames; Organism; Pathogenicity; Pathology; Phenotype; Phylogenetic Analysis; Principal Investigator; Printing; Process; Property; Purpose; Range; Reading; Refractory; Research; Research Personnel; Resources; Role; Shotguns; Specificity; Standards of Weights and Measures; Study models; Time; Tissues; Variant; Virulence; Work; base; comparative; comparative genomic hybridization; design; functional genomics; genetic analysis; genome sequencing; infectious disease evolution; intracellular parasitism; member; microbial; novel; pathogen; professor; research study; tool

We intend to extend genomics from the characterization of individual bacterial genomes to characterizing the evolution of infectious disease-causing bacteria. The Chlamydiales, an order of Gram-negative obligate intracellular pathogens, are ideally suited to this approach. Members of this order cause a range of diseases but continue to be refractory to conventional genetic analyses. Our novel, multifaceted approach, which we have named "Taxogenomics", is to first sequence the type strains of the Chlamydiaceae species not addressed by previous or current projects - C. suis, C. pecorum, and C. psittaci (a potential biological warfare agent). Additionally, we will sequence the koala strain of C. pneumoniae and the most evolutionarily distant members of the Chlamydiales, Waddlia chondrophila and Simkania negevensis. To identify those genes which may have been lost by the laboratory adapted type strains or been acquired by "wild" isolates, we will apply subtractive hybridization by pooling multiple isolates from each species and subtracting those genes shared by the type strain. With sequences from representatives of all genomes and with sequences derived from the taxonomic genomic subtractions, we will then create a gene database of all known ORFs from this evolutionarily isolated family. We will use this database to design a non-redundant microarray of Chlamydiales gene variation (called here the "Taxochip"). In this study, we will use the Taxochip in a suite of comparative genomic hybridization (CGH) experiments using a unique set of diverse Chlamydiales isolates that we have compiled from around the globe. We expect to use this genome data to investigate the evolution of the Chlamydiales and identify those genes that may differentiate the variety of observed host/tissue niches and resulting disease outcomes. We also will assess the potentially important role of horizontal gene transfer in creating novel pathogenicity phenotypes and the likely important relationship between animal and human chlamydial strains. Additionally, the Taxochip design and the Chlamydiales gene database will be of long-term benefit to all chlamydiologists and molecular evolutionists who are increasingly using the Chlamydiales as a standard model for studying reductive evolutionary processes. This study is designed to address broad questions that deal with the genetic and evolutionary basis of the development of intracellular parasitism and pathogenicity in the Chlamydiales. With broad and international support from the scientific community, we consider this a groundbreaking proposal and anticipate it will be a benchmark study in comparative microbial genomics.

我们打算将基因组学从单个细菌基因组的表征扩展到表征 传染病致病细菌的进化。衣原体，一个革兰氏阴性专性细胞内 病原体非常适合这种方法。该目的成员引起一系列疾病，但仍然是 传统的遗传学分析。 我们的新的、多方面的方法，我们命名为“Taxogenomics”，是首先对典型菌株进行测序， 以前或目前的项目没有涉及的衣原体科物种- C。suis，C. pecorum和C.鹦鹉热 潜在的生物战剂）。此外，我们将测序考拉菌株的C。肺炎和大多数 衣原体目、Waddlia chondrophila和Simkania negevensis的进化上遥远的成员。以识别 这些基因可能已经丢失的实验室适应型菌株或获得的“野生”分离，我们 我将应用消减杂交技术，将来自每个物种的多个分离株合并，然后减去那些共有的基因 由典型菌株。用来自所有基因组的代表的序列和来自 分类基因组消减，然后我们将创建一个基因数据库的所有已知的ORF从这个进化 孤立的家庭。我们将使用这个数据库来设计一个非冗余的衣原体基因变异的微阵列（称为 这里是“Taxochip”）。在本研究中，我们将Taxochip用于一套比较基因组杂交（CGH）技术中 使用我们从地球仪收集的一组独特的不同衣原体分离株进行实验。 我们希望利用这些基因组数据来研究衣原体的进化并鉴定这些基因 这可以区分观察到的宿主/组织小生境的多样性和导致的疾病结果。我们还将评估 水平基因转移在创造新的致病性表型中的潜在重要作用， 动物和人类衣原体菌株之间重要关系。此外，Taxochip设计和 衣原体基因数据库的建立将使所有的衣原体学家和分子进化学家长期受益， 越来越多地使用衣原体作为研究还原进化过程的标准模型。 这项研究旨在解决广泛的问题，处理的遗传和进化的基础， 衣原体细胞内寄生和致病性的发展。在广泛的国际支持下， 从科学界来看，我们认为这是一个开创性的建议，并预计这将是一个基准研究 比较微生物基因组学