A Novel Technology to Image Human Oral Microbial Communities

人类口腔微生物群落成像新技术

基本信息

批准号：
7612321
负责人：
Alex M Valm
金额：
$ 2.76万
依托单位：
BROWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-29 至 2011-09-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7612321
关键词：
Algorithms Arts Bacteria Bacterial Infections Biological Assay Cardiovascular Diseases Censuses Communities Complex Data Data Analyses Dental caries Detection Development Disease Ecology Fluorescence Fluorescence Microscopy Fluorescent in Situ Hybridization Fluorochrome Fostering Gingivitis Goals Health Human Image Imagery Imaging Techniques Imaging technology In Situ In Situ Hybridization Individual Infection Infection Control Label Low Birth Weight Infant Lung Messenger RNA Metabolic Methods Microbe Molecular Monitor Numbers Oligonucleotide Probes Oral Oral cavity Periodontitis Phylogenetic Analysis Pregnancy Outcome Proteins Protocols documentation Relative (related person)Reporter Research Ribosomal RNA Systemic disease Taxon Techniques assay development combinatorial community organizations design image processing member microbial microbial community new technology novel oral bacteria oral biofilm research study technology development tool

项目摘要

DESCRIPTION (provided by applicant): The objective of this proposal is to develop a novel combinatorial labeling and detection technology for imaging and distinguishing between most if not all of the members of the human oral microbiological community. Fluorescence In Situ Hybridization (FISH) for 16S rRNA sequences will visually identify individual members of the microbial community either as collected or in situ. The capabilities of FISH will be extended by employing a combination of fluorescent reporter groups to create "spectral signatures" that allow simultaneous encoding and imaging of tens to hundreds of different microbial phylotypes. Enhanced, state-of-the-art spectral imaging techniques will record the spectral signatures. Novel algorithms will be developed to deconstruct spectral signatures of labeled microbes. This new imaging capability will allow a comprehensive census of phylotypes in the human oral microbial community as well as determination of the spatial organization of this community. In principle, the combinatorial labeling strategy could be extended by simultaneously labeling microbes with probes against 16S rRNA for phylogenetic identification and probes against mRNA or proteins for metabolic or structural information. The capability to assess the relative abundance, organization and function of particular microbes will open new avenues for comprehensive and detailed study of the ecology of the oral microbial community. Oral microbes are implicated in diseases such as caries, gingivitis, and periodontitis, which are among the most common bacterial infections in humans, as well as systemic diseases including cardiovascular disease, pulmonary infections, and low birth-weight and pre-term pregnancy outcome. No single microbial species is implicated as the etiological agent of these diseases, rather, it is hypothesized that the complex association of multiple microbial phylotypes in communities are responsible for maintaining health and causing disease. Development of the technology proposed here will allow a comprehensive understanding of the normal human oral flora and foster the development of new and effective strategies to study, monitor, and control infection.

描述（由申请人提供）：本提案的目的是开发一种新颖的组合标记和检测技术，用于成像和区分人类口腔微生物群落的大多数（如果不是全部）成员。 16S rRNA 序列的荧光原位杂交 (FISH) 将直观地识别收集的或原位的微生物群落的个体成员。 FISH 的功能将通过使用荧光报告基团的组合来扩展，以创建“光谱特征”，从而允许同时编码和成像数十到数百种不同的微生物系统型。增强的、最先进的光谱成像技术将记录光谱特征。将开发新的算法来解构标记微生物的光谱特征。这种新的成像能力将允许对人类口腔微生物群落的系统发育型进行全面普查，并确定该群落的空间组织。原则上，组合标记策略可以通过同时使用针对 16S rRNA 的探针进行系统发育鉴定和针对 mRNA 或蛋白质的探针进行标记来扩展，以获取代谢或结构信息。评估特定微生物的相对丰度、组织和功能的能力将为全面、详细地研究口腔微生物群落的生态学开辟新的途径。口腔微生物与龋齿、牙龈炎和牙周炎等人类最常见的细菌感染等疾病以及心血管疾病、肺部感染、低出生体重和早孕结局等全身性疾病有关。没有单一的微生物物种被认为是这些疾病的病因，相反，人们假设群落中多种微生物系统型的复杂关联负责维持健康和引起疾病。这里提出的技术的发展将使人们能够全面了解正常的人类口腔菌群，并促进开发新的有效策略来研究、监测和控制感染。