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）：人类口腔中栖息着极其复杂的微生物群落，这些微生物群落在人类健康和疾病中发挥着关键作用。人们越来越认识到，可能必须以精细的分辨率探索独特微生态位中微生物群落的空间组织，以便为阐明群落组装和功能的规则以及了解它们在疾病中的作用提供基础。尽管下一代 DNA 测序技术和宏基因组学彻底改变了微生物群落的分析，但我们理解中的一个主要差距是缺乏微米级的空间信息——更好地表征微生物群落成员之间相互关系所必需的信息（微生物相互作用组）以及与宿主组织的关系。我们建议通过海洋生物实验室的鲍里西实验室与福赛思研究所和哈佛医学院的杜惠斯特实验室之间的新型合作来填补这一空白。 Borisy 实验室最近开发了一种组合标记和光谱成像 (CLASI) 策略，用于在单个显微图像中同时识别数十个微生物类群。杜惠斯特实验室对人类口腔微生物群进行了开创性的宏基因组研究。两个实验室在 ARRA 挑战拨款的支持下进行了初步合作，将 CLASI 策略应用于人类牙菌斑（一种微生物生物膜）的分析，并发表了一份“原理验证”出版物，该出版物描述了两者的接近性 15个口腔类群的关系。在此基础上，我们提出的研究将可视化和定义 9 个口腔生态位的口腔微生物组结构和相互作用组的微米级生物地理学：龈下菌斑、龈上菌斑、角化牙龈、硬腭、舌背、颊粘膜、腭扁桃体、喉咙和唾液。它将采用自动瓷砖扫描功能，记录牙周疾病中龈下微生物的结构和相互作用组，展示该方法在检查其他口腔疾病时的实用性。它将为口腔研究界生产一套经过验证的 FISH 探针。通过揭示口腔微生物组的精确微米级结构，这项研究将解决群落动态的基本机制和原理。它将为人类口腔微生物群成员的组织方式提供前所未有的系统级理解，并为未来研究正常微生物菌群在健康和患病口腔中的作用奠定基础。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界。该项目应该能够确定关键的细菌相互作用，这些相互作用可以作为治疗干预的新目标。