A Foundation for the Oral Microbiome and Metagenome

描述(由申请人提供)：口腔研究界的一个主要目标是了解微生物-微生物和微生物-宿主相互作用如何影响人类健康和疾病。拟议的研究将使研究界能够通过提供以下研究资源来实现这一目标：人类口腔微生物组数据库(HOMD)，一个可上网的分类学和基因组数据库，其中包括口腔分类描述和微生物组分析工具；150个以前未培养的口腔细菌的参考菌株，以促进体内和体外实验；以及目前缺乏遗传信息的100个口腔分类群的基因组。第一个目标将提供并扩大口腔细菌的临时命名方案(分类法)，包括那些尚未正式命名或培养的细菌。HOMD将扩展到描述1000多个人类口腔分类群，并将纳入人类微生物组计划对9个口腔部位进行深度16S rRNA测序的结果。完成这一目标将使研究人员能够将表型、临床、基因组和书目信息与基于16S rRNA序列的准确定义的口腔分类群联系起来。在400个最流行的口腔分类群中，近三分之一没有已知的栽培分离物，第二个目标解决了这个问题。这些分离物将通过16S rRNA测序进行鉴定，这些分离物来自调查人员坦纳和韦德的培养样本，以及L.V.霍尔德曼·摩尔和已故弗吉尼亚理工学院埃德·摩尔的样本，该学院目前位于福赛斯研究所。不同菌门的目标菌株，如TM7、Chlorobi、SR1和其他菌株，将在联合体中培养，并在可能的情况下，使用我们描述的方法在纯培养中分离。代表以前未培育物种的分离株将允许研究人员研究体外生物膜生长，开发遗传系统，并进行动物模型实验。第三个目标将获得目前缺乏基因组信息的150个口腔分类群的基因组序列。它还将为口腔细菌提供元基因组序列，这些细菌可以在联合体中生长，但不能在纯培养中生长。该项目将完成几乎所有400种最流行的口腔细菌的参考基因组的生产。这些信息将成为解释元基因组数据、生产用于转录组研究的微阵列以及用于从基因组编码生成蛋白质组研究的蛋白质片段文库的永久资源。由该项目产生的基因组信息、工具和菌株将作为研究口腔微生物组在人类健康和疾病中的作用的永久基础和资源。

DESCRIPTION (provided by applicant): A major goal of the oral research community is to understand how microbe-microbe and microbe- host interactions affect human health and disease. The proposed research will enable the research community to reach this goal by providing the following research resources: the Human Oral Microbiome Database (HOMD), a web accessible taxonomic and genomic database with oral taxon descriptions and microbiome analysis tools; reference strains for 150 previously uncultured oral bacteria to facilitate in vivo and in vitro experimentation; and genomes for 100 oral taxa that currently lack genetic information. The first Aim will provide and expand a provisional naming scheme (taxonomy) for oral bacteria, including those that have not been formally named or cultivated. HOMD will be expanded to describe over 1,000 human oral taxa, and will incorporate results from the Human Microbiome Projects deep 16S rRNA sequencing of nine oral cavity sites. Completion of this aim will allow investigators to link phenotypic, clinical, genomic and bibliographic information to precisely defined oral taxa based on 16S rRNA sequences. Nearly one-third of the 400 most prevalent oral taxa have no known cultivated isolate and the Second Aim addresses this issue. Such isolates will be identified by 16S rRNA sequencing from the culture collections of investigators Tanner and Wade, and from the collection of L. V. Holdeman Moore and the late Ed Moore, Virginia Polytechnic Institute, now housed at The Forsyth Institute. Targeted isolates for diverse phyla such as TM7, Chlorobi, SR1 and others will be grown in consortia and isolated in pure culture, where possible, using methods we have described. Isolates representing previously uncultivated species will allow investigators to study of in vitro biofilm growth, develop genetic systems, and perform animal model experiments. The Third Aim will obtain genome sequences for 150 oral taxa currently lacking genome information. It will also provide metagenome sequences for oral bacteria that can grow in consortia but not in pure culture. This project will complete the production of reference genomes for nearly all the 400 most prevalent oral bacteria. This information will be a permanent resource for interpretation of metagenome data, for the production of microarrays for transcriptome studies, and for generating protein fragment libraries from genomic coding for proteomic studies. The genome information, tool, and strains generated by this project will serve as a permanent foundation and resource for investigations on the role of the oral microbiome in human health and disease.