Community Genomics of the Human Oral Microbiome

描述：人类口腔是一个复杂的&gt；700微生物群落的家园，在口腔健康和疾病中发挥着核心作用。在我们的应用中，这个口腔微生物群落或口腔微生物群被视为一个单一的动态实体，其行为和组成在空间(不同个体的不同口腔生态位)、时间和扰动之间存在差异。尽管这一群体在维持人类健康和引发口腔疾病方面至关重要，但其行为的遗传基础尚未得到很好的探索。这项应用的长期目标是在基因组水平上全面了解口腔微生物群落，以便促进口腔健康，改善或预防疾病。我们将通过表征健康牙周和粘膜组织受试者口腔微生物组中相对基因和基因组的丰度和基因表达来实现这些目标，然后将我们的分析扩展到与慢性牙周病相关的口腔微生物组。来自这一应用的数据不仅将用于建立口腔微生物组中的基因数据库，而且还将导致探索基因丰度和表达以及检查微生物组与人类宿主的相互作用的新的实验范式。 这项应用的具体目的是：目的1.鉴定健康人口腔微生物组的基因和基因组内容。我们的方法包括高通量测序随机和目标质粒和融合基因文库，以及功能基因和基因家族的分类。目的2.研究与慢性牙周炎相关的口腔微生物组的基因和基因组含量。目的3.开发用于口腔微生物组数据的社区基因组工具。将创建一个口腔微生物组基因数据库，供科学界使用。将开发一个高密度DNA微阵列，其中约有2,000个基因在AIMS 1和2中识别，最终目标是识别预测临床自然病史和操作反应的基因丰度和表达模式。这项工作的预期长期好处之一将是对人类口腔生态系统的革命性理解，以及口腔疾病分类和管理的新方法。

DESCRIPTION: The human oral cavity is home to a complex community of >700 microorganisms with a central role in oral health and disease. In our application, this oral microbial community, or oral microbiome, is viewed as a single dynamic entity, with variation in its behavior and composition across space (different oral niches in different individuals), time, and with perturbation. Despite the critical importance of this community in maintaining human health and provoking oral disease, the genetic basis for its behavior has not been well explored. The long-term objectives of this application are to develop a comprehensive understanding of the oral microbial community at the genomic level so that oral health can be promoted, and disease ameliorated or prevented. We will address these goals by characterizing relative gene and genome abundance and gene expression in the oral microbiome in subjects with healthy periodontal and mucosal tissues, and then extend our analysis to the oral microbiome associated with chronic periodontal diseases. Data from this application will not only be used to build a database for genes in the oral microbiome, but will also lead to new experimental paradigms for exploring gene abundance and expression, and examining the interaction of the microbiome with the human host. The Specific Aims of this application are: Aim 1. Characterize the gene and genome content of the healthy human oral microbiome. Our approaches include high-throughput sequencing of random and targeted plasmid and fosmid genomic libraries and classification of functional genes and gene families. Aim 2. Characterize the gene and genome content of the oral microbiome associated with chronic periodontitis. Aim 3. Development of community genomic tools for oral microbiome data. An oral microbiome gene database will be created for use by the scientific community. A high-density DNA microarray with approximately 2,000 genes identified in Aims 1 and 2 will be developed with the ultimate goal of identifying patterns of gene abundance and expression that predict clinical natural history and response to manipulation. Among the expected long-term benefits of this work will be a revolutionized understanding of the human oral ecosystem and new approaches for classification and management of oral diseases.