Development of genetic systems for human-associated methanogens

人类相关产甲烷菌遗传系统的开发

基本信息

批准号：
9019330
负责人：
WILLIAM W METCALF
金额：
$ 18.92万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-01-15 至 2017-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9019330
关键词：
Address Alleles Archaea Atherosclerosis Complex DNA DNA cassette Data Development Electroporation Equipment Fermentation Gene Targeting Genetic Genetic Transcription Genomics Glean Goals Growth Health Human Human Resources Inflammatory Inflammatory Bowel Diseases Intestinal Cancer Knowledge Link Liposomes Malignant Neoplasms Mediating Metabolic Methane Methanobacteria Methanobrevibacter Methods Nature Obesity Organism Oxygen Periodontal Diseases Personal Satisfaction Process Research Resistance Resources Role Series System Techniques Testing Transfection bacterial resistance cytokine genetic analysis genetic manipulation high reward high risk man member method development microbiota microorganism next generation sequencing nutrition pan-genome public health relevance research study resistance gene tool transcriptome sequencing transcriptomics

项目摘要

DESCRIPTION (provided by applicant): The goal of this high-risk/high-reward project is to develop the tools needed for experimental manipulation of human-associated methanogens. These commensal microorganisms colonize all humans, making significant contributions to host nutrition and overall health. The metabolic interactions between methanogens and other members of the human microbiota strongly influence the efficiency of the digestive process, as well as the colonic fermentation products that are absorbed by the host. Moreover, some human-associated methanogens are potent inducers of inflammatory cytokines, while others produce metabolites linked to the development of atherosclerosis and cancer. Given these observations, it is not surprising that methanogen carriage is correlated with a number of pathological conditions including obesity, inflammatory bowel disease, intestinal cancers and periodontal disease. Numerous hypotheses have been put forward to explain the linkage between methanogens and these health issues; unfortunately, experimental support for these ideas is exceedingly scarce. Three factors have contributed to this scarcity. First, all methanogens are exquisitely sensitive to oxygen and require specialized anaerobic techniques that are not widely employed; second, methods for genetic manipulation of human-associated methanogens are non-existent; and third, methanogen research has traditionally been restricted to the environmental and energy related topics. We propose to remedy this situation for the three of the dominant species of human-associated methanogens: Methanobrevibacter smithii, Methanospheara stadtmanae and the recently discovered Methanomassiliicoccus luminyensis. To achieve this goal we propose to develop genetic systems for human-associated methanogens and to acquire the genomic and transcriptomic resources needed to inform and direct the ongoing genetic analyses of these important microorganisms.

描述（由申请人提供）：这个高风险/高回报项目的目标是开发对人类相关产甲烷菌进行实验操作所需的工具，这些共生微生物在全人类中定殖，为宿主营养和整体健康做出重大贡献。产甲烷菌和人类微生物群其他成员之间的代谢相互作用强烈影响消化过程以及宿主吸收的结肠发酵产物的效率。产甲烷菌是炎症细胞因子的有效诱导剂，而其他产甲烷菌则产生与动脉粥样硬化和癌症发展相关的代谢物，鉴于这些观察结果，产甲烷菌携带与许多病理状况相关，包括肥胖、炎症性肠病、肠癌和癌症，也就不足为奇了。人们提出了许多假设来解释产甲烷菌与这些健康问题之间的联系；不幸的是，这些想法的实验支持极其缺乏，首先，所有产甲烷菌都对氧气极其敏感，需要专门的厌氧技术，但这些技术并未得到广泛应用；其次，不存在与人类相关的产甲烷菌的基因操作方法；第三，产甲烷菌研究传统上仅限于环境和能源相关主题；我们建议针对与人类相关的产甲烷菌的三种主要物种：Methanobrevibacter smithii、Methanospheara stadtmanae 和最近发现的 Methanobrevibacter smithii 来纠正这种情况。为了实现这一目标，我们建议开发人类相关产甲烷菌的遗传系统，并获取为这些重要微生物的持续遗传分析提供信息和指导所需的基因组和转录组资源。