Development of genetic systems for human-associated methanogens

人类相关产甲烷菌遗传系统的开发

• 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
• 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

 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人类相关产甲烷菌实验操作所需的工具。这些共生微生物寄生在全人类身上，为宿主的营养和整体健康做出了重大贡献。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的效率以及宿主吸收的结肠发酵产物。此外，一些与人类相关的产甲烷菌是炎症细胞因子的有效诱导剂，而另一些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、肠癌和牙周病）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。三个因素造成了这种稀缺。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，但目前尚未广泛采用；其次，不存在对人类相关产甲烷菌进行基因操作的方法；第三，产甲烷菌研究传统上仅限于环境和能源相关主题。我们建议针对人类相关产甲烷菌的三种主要物种：史密斯甲烷短杆菌（Methanobrevibacter smithii）、Stadtmanae 甲烷球菌（Methanospheara stadtmanae）和最近发现的发光甲烷甲烷菌（Methanomassiliicoccus luminyensis）来纠正这种情况。为了实现这一目标，我们建议开发与人类相关的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。