Genomic Tools For Studying The Ecology Of The Human Vaginal Microflora

研究人类阴道菌群生态学的基因组工具

• 批准号: 7846560
• 负责人: Jacques Ravel
• 金额: $ 1.44万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-05 至 2009-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7846560
• 关键词: Address; Affect; African American; Age; Algorithms; Arts; Asians; Bacteria; Bacterial Vaginosis; Biochemical; Biological Assay; Cataloging; Catalogs; Caucasians; Caucasoid Race; Chemicals; Clinical; Collection; Communicable Diseases; Communities; Computer software; DNA; Data; Data Analyses; Databases; Detection; Development; Devices; Disease; Disease susceptibility; Doctor of Philosophy; Ecology; Ecosystem; Environment; Epidemiologic Studies; Estradiol; Ethnic group; Etiology; Evaluation Studies; Evolution; Future; Gene Cluster; Gene Expression; Gene Expression Profiling; Gene Library; Genes; Genetic; Genome; Genomics; Glycogen; Goals; Health; High Prevalence; Hispanics; Human; Human Genome Project; Individual; Infection; Laboratories; Libraries; Maintenance; Measures; Messenger RNA; Metabolic; Methods; Molecular; Monitor; North America; Oligonucleotide Microarrays; Oligonucleotides; Online Systems; Open Reading Frames; Oral cavity; Organism; Pathway interactions; Phylogenetic Analysis; Physicians; Play; Preparation; Process; Progesterone; Recombinant DNA; Relative (related person); Research; Research Ethics Committees; Research Personnel; Restriction Fragment Length Polymorphism Analysis; Restriction fragment length polymorphism; Ribosomal RNA; Risk; Role; Sampling; Sequence Analysis; Serum; Sexually Transmitted Diseases; Shotgun Sequencing; Soil; Specimen; Structure; Surveys; Swab; System; Testing; Urinary tract infection; Vagina; Vaginal Diseases; Variant; Water; Woman; Women' s Health; Work; Yeasts; base; comparative; cost; density; design; functional genomics; gene discovery; gene function; high risk; homologous recombination; human ecology; insight; member; microbial; microbial community; microbial genome; microbiome; microorganism; prevent; programs; rRNA Genes; rapid detection; reconstruction; reproductive; reproductive hormone; tool

DESCRIPTION (provided by applicant): The normal vaginal microflora in healthy women of reproductive age plays a key role in preventing successful colonization by "undesirable" organisms including those responsible for bacterial vaginosis, yeast infections, sexually transmitted diseases and urinary tract infections. Our long-term goal is to develop an accurate understanding of the composition and ecology of the vagina microbial ecosystem in normal, healthy women as an essential prerequisite for comprehending how the normal microflora reduces the risk of acquiring these communicable diseases and for defining the factors determining disease susceptibility. The specific hypotheses are that 1. women's genetic backgrounds influence the composition of the vaginal microflora, 2. while vaginal community compositions markedly vary amongst women, the functional potential of a community is similar. Tools necessary to test these hypotheses will be developed and are addressed by these specific aims: 1. Conduct a comprehensive survey of the vaginal microflora in 400 women of different ethnic background using 16S rRNA gene sequencing analysis. We will correlate the community composition with genetic background, and provide the basis for Aim 2. 2. Develop a 16S rDNA-based molecular tool (molecular inversion probes) to rapidly and quantitatively measure the microbial species composition and abundance of a vaginal community. 3. Characterized the metabolic potential of the vaginal microflora of healthy women by community genomics. We will sequence the "community genome" of the five most predominant community types. Sequence data and analysis will be freely accessible through the web-based Vaginal Microbiome Database. 4. Develop the Vaginal Microbiome Expression GeneChip(c) array, a high density oligonucleotide microarray- based tool for functional genomic analyses of vaginal microbial communities. Using this tool we will assess community gene expression over the course of two months, while monitoring reproductive hormone levels. We view this work as analogous to the human genome project, in which initial sequence information provided a platform for decades of future work focused on all aspect of human health and disease. Similarly, these tools will be critical for the study and evaluation of women's health.

描述（由申请人提供）：健康育龄女性的正常阴道微生物群在防止“不良”微生物成功定植方面发挥着关键作用，这些“不良”微生物包括导致细菌性阴道病、酵母菌感染、性传播疾病和尿路感染的微生物。我们的长期目标是准确了解正常健康女性阴道微生物生态系统的组成和生态，这是理解正常微生物群如何降低感染这些传染病的风险以及确定疾病易感性决定因素的重要先决条件。具体假设是：1. 女性的遗传背景影响阴道微生物群的组成，2. 虽然女性之间的阴道菌群组成明显不同，但菌群的功能潜力是相似的。将开发测试这些假设所需的工具，并通过以下具体目标来解决： 1. 使用 16S rRNA 基因测序分析对 400 名不同种族背景的女性的阴道微生物群进行全面调查。我们将把群落组成与遗传背景联系起来，为目标2提供基础。 2.开发基于16S rDNA的分子工具（分子倒置探针），以快速定量测量阴道群落的微生物物种组成和丰度。 3. 通过群落基因组学表征健康女性阴道微生物群的代谢潜力。我们将对五种最主要的群落类型的“群落基因组”进行测序。序列数据和分析将可通过基于网络的阴道微生物组数据库免费访问。 4. 开发阴道微生物组表达 GeneChip(c) 阵列，这是一种基于高密度寡核苷酸微阵列的工具，用于阴道微生物群落的功能基因组分析。使用这个工具，我们将评估两个月内的社区基因表达，同时监测生殖激素水平。我们认为这项工作类似于人类基因组计划，其中初始序列信息为未来数十年专注于人类健康和疾病各个方面的工作提供了一个平台。同样，这些工具对于女性健康的研究和评估也至关重要。