Healing Mucosa, interaction of microbial ecology and the immune system

治愈粘膜、微生物生态与免疫系统的相互作用

• 批准号: 237602025
• 负责人: Professor Dr. Martin von Bergen
• 金额: --
• 依托单位: Department Molekulare Systembiologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/237602025?language=en
• 关键词: Healing; Mucosa; interaction; microbial; ecology

The maintenance of the stable and healthy symbiosis between microbiota and the host depends on the composition ofthe microbiota which In turn Is controlled by immunological and metabolic factors. Both the Immunological as well as the metabolic synapse are located In the contact zone between microbiota and the host's tissue, the mucus layer. Hence we will focus on the analysis of this specific habitat. It Is reported that the phylogeny and the metabolic functionality are significantly different between the mucus layer and the gut content. The production and maintenance ofthe mucus layer Is known to be strongly affected by Inflammatory diseases like chemically Induces colitis. The Immune response ofthe host Influences directly the composition of the microbiota which then affects metabolic processes. The latter are resulting from the complex metabolic Interdependencles within the microbiota and demand thereby for the analysis of the functional rather than for an assessment of the mere phylogenle diversity. This can be achieved by applying metaproteomlcs and especially protein-stable Isotope probing as a well established variation of metaproteomlcs, In this technique 13C and 15N labelled substrates will be applied and the Incorporation of these Isotopes into proteins determined by high resolution mass spectrometry. The identification of peptides and the according proteins on the basis of metagenome data provides simultaneously phylogenle and functional Information. The degree of Incorporation Is used as a measure of metabolic activity. Furthermore the shape of the isotopologlc distribution allows distinguishing between direct and Indirect metabollsation and hence supports the information on the carbon and nitrogen flux through the microbiota. In addition also the flux from the microbiota Into the host tissue can be assessed. The effect on the metabolic synapse will be also followed by metabolomic profiling ofthe host serum. Since also the endothelium Is crucially Involved in the metabolic synapse and It Is affected by the Inflammatory response we will also analyze the proteomic effects In these cells In colitis In comparison to healthy tissue. The global quantitative proteomics will Indicate the general pathways of the molecular response whereas the phospoproteomlcs approach will lead to Insights Into the cellular signaling Induced by colitis. In summary, we will Identify metabolic pathways and interactions within the mlcroblata and the effect on the metabolic synapse caused by colitis and will combine this with insights Into the response of endothelial cells. Furthermore we will offer proteomic and metaproteomlc support to other subprojects within the SPP.

微生物群与宿主之间的稳定和健康共生关系的维持取决于微生物群的组成，而微生物群的组成又受免疫和代谢因素的控制。免疫突触和代谢突触都位于微生物群与宿主组织的接触区，即黏液层。因此，我们将重点分析这个特定的栖息地。据报道，黏液层和肠道内容物的系统发育和代谢功能有显著差异。众所周知，黏液层的产生和维持受到化学诱导结肠炎等炎症性疾病的强烈影响。宿主的免疫反应直接影响微生物群的组成，进而影响代谢过程。后者是由微生物群内复杂的代谢相互依赖引起的，因此需要对功能进行分析，而不仅仅是对系统进化多样性的评估。这可以通过应用元蛋白质组学，特别是蛋白质稳定同位素探测作为元蛋白质组学的一种完善的变异来实现。在这项技术中，13C和15N标记的底物将被应用，这些同位素的掺入将通过高分辨率质谱测定。基于宏基因组数据的多肽和相应蛋白的鉴定同时提供了系统发育和功能信息。掺入度被用来衡量代谢活动。此外，同位素分布的形状可以区分直接代谢和间接代谢，从而支持通过微生物群的碳和氮通量的信息。此外，还可以评估微生物群进入宿主组织的通量。对代谢突触的影响也将被宿主血清的代谢组学分析所遵循。由于内皮在代谢突触中起着至关重要的作用，并且受到炎症反应的影响，我们还将分析结肠炎中这些细胞的蛋白质组学效应，并将其与健康组织进行比较。全球定量蛋白质组学将表明分子反应的一般途径，而磷蛋白质组学方法将导致对结肠炎诱导的细胞信号传导的深入了解。总之，我们将确定代谢途径和结肠炎对代谢突触的影响，并将其与内皮细胞的反应结合起来。此外，我们将为SPP内的其他子项目提供蛋白质组学和元蛋白质组学支持。