Spatial Organization of the Oral Microbiome

口腔微生物组的空间组织

• 批准号: 8766782
• 负责人: Gary G Borisy
• 金额: $ 34.31万
• 依托单位: ADA FORSYTH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-12-03 至 2017-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8766782
• 关键词: Address; Architecture; Area; Biological; Cell Communication; Cell Count; Cells; Collaborations; Communities; Confocal Microscopy; DNA Sequence; Dental Plaque; Development; Disease; Environmental Microbiology; Fluorescent in Situ Hybridization; Foundations; Future; Gingiva; Goals; Grant; Grouping; Hard Palate; Health; Human; Human Microbiome; Image; Image Analysis; Imagery; Imaging Techniques; Individual; Institutes; Label; Laboratories; Lead; Length; Lesion; Marines; Metagenomics; Methacrylates; Methods; Microbe; Microbial Biofilms; Microscopic; Molecular; Mouth Diseases; Oral; Oral cavity; Oral mucous membrane structure; Palatine Tonsil; Patients; Periodontal Diseases; Periodontal Pocket; Periodontitis; Pharyngeal structure; Play; Positioning Attribute; Procedures; Publications; Publishing; Research; Resolution; Role; Saliva; Sampling; Scanning; Site; Slide; Solid; Structure; System; Taxon; Technology; Therapeutic Intervention; Tissues; Tooth structure; Width; base; combinatorial; computerized tools; design; fluorescence imaging; in vivo; innovation; medical schools; member; microbial; microbial community; microbiome; microorganism; millimeter; next generation; novel; oral biofilm; oral microbiome; oral plaque; research study; screening; spatial relationship; subgingival biofilm; tongue dorsum; tool

DESCRIPTION (provided by applicant): The human mouth is colonized by a microbial community of enormous complexity that plays a key role in human health and disease. Increasingly, it is recognized that the spatial organization of microbial communities in unique micro-niches may have to be explored at fine resolution to provide the basis for elucidating the rules of community assembly and function and to understand their role in disease. Although next-generation DNA sequencing technology and metagenomics have revolutionized the analysis of microbial communities, a major gap in our understanding is the lack of spatial information at the micron level,--information necessary to better characterize the interrelationships between members of a microbial community (the microbial interactome) and with host tissue. We propose to fill this gap through a novel collaboration between the Borisy lab at the Marine Biological Laboratory and the Dewhirst lab at the Forsyth Institute and Harvard Medical School. The Borisy lab has recently developed a Combinatorial Labeling and Spectral Imaging (CLASI) strategy for the simultaneous identification of tens of microbial taxa in a single microscopic image. The Dewhirst lab has carried out ground-breaking metagenomic studies of the human oral microbiota. An initial collaboration between the two laboratories, supported by an ARRA Challenge Grant, applied the CLASI strategy to the analysis of human dental plaque, a microbial biofilm, and led to a "proof-of-principle" publication that characterized the proximity relationships of 15 oral taxa. Building on this foundation, our proposed research will visualize and define the micron-scale biogeography of the oral microbiome structure and interactome for 9 oral niches: subgingival plaque, supragingival plaque, keratinized gingivae, hard palate, tongue dorsum, buccal mucosa, palatine tonsils, throat, and saliva. Employing an automated tile-scanning capability, it will document the architecture and interactome for subgingival microbes in periodontal disease, demonstrating the utility of the approach for examining other oral diseases. It will produce a validated set of FISH probes for the oral research community. By revealing the precise, micron-scale structure of the oral microbiome, this research will address fundamental mechanisms and principles of community dynamics. It will provide an unprecedented systems-level understanding for how members of the human oral microbiota are organized and it will lay the foundation for future studies examining the role of the normal microbial flora in both healthy and diseased mouths. It will impact the broader oral and microbial research communities by developing methods, analysis tools and probes. This project should lead to the identification of key bacterial interactions that may serve as novel targets for therapeutic intervention.

描述（由申请人提供）：人口是由一个巨大复杂性的微生物社区殖民的，在人类健康和疾病中起着关键作用。人们越来越多地认识到，在独特的微型社会中，微生物群落的空间组织可能必须以精细的分辨率进行探索，以提供阐明社区组装和功能规则并了解其在疾病中的作用的基础。尽管下一代DNA测序技术和宏基因组学彻底改变了对微生物群落的分析，但我们理解的主要差距是在微米级别缺乏空间信息，这是更好地表征微生物群落成员（微生物相互作用组）和与宿主组织之间相互关系所必需的信息。我们建议通过在海洋生物实验室的Borisy Lab与Forsyth Institute和Harvard Medical School的DeWhirst Lab之间进行新颖的合作来填补这一空白。 Borisy Lab最近开发了一种组合标记和光谱成像（CLASI）策略，用于同时鉴定单个显微镜图像中的数十个微生物分类群。 DeWhirst实验室已经对人口腔微生物群进行了突破性的宏基因组学研究。两个实验室之间的最初合作，在ARRA挑战赠款的支持下，将CLASI策略应用于人类牙齿斑块，一种微生物生物膜，并导致了“原理证明”的出版物，这些出版物表现了邻近性的特征 15个口腔分类单元的关系。在这个基础的基础上，我们提出的研究将可视化和定义9口腔壁画的口腔微生物组结构和互动组的微米尺度生物地理学：subgingival斑块，上斑块，角质斑块，角质化的金格，硬帕拉特，硬帕拉特，舌头，舌头，颊muc骨，毛cal虫，毛palatine tonsils tonsils tonsils tonsils saliva。它具有自动化的瓷砖扫描能力，它将记录牙周疾病中尺寸微生物的体系结构和相互作用，这证明了检查其他口腔疾病的方法。它将为口腔研究社区生成一组经过验证的鱼类探针。通过揭示口腔微生物组的精确，微观尺度的结构，这项研究将解决社区动态的基本机制和原理。它将为人类口腔微生物群的成员如何组织起来提供前所未有的系统级别的理解，并为未来的研究奠定基础，以研究正常微生物菌群在健康和患病的口腔中的作用。它将通过开发方法，分析工具和探针来影响更广泛的口腔和微生物研究社区。该项目应导致对关键细菌相互作用的识别，这些相互作用可能是治疗干预的新靶标。