- MIMIC -Culture-based and molecular study of the mouse gut microbiometowards Minimal Microbial Consortia

肠道微生物区系对哺乳动物寄主生理非常重要。因此，努力了解其结构和功能至关重要。组学技术在微生物组研究方面取得了重大突破，但它们只显示出相关性。为了测试因果关系和研究分子机制，小鼠模型已被广泛用于世界各地的许多研究项目和SPP1656。然而，小鼠肠道微生物组的细菌菌株和基因组明显不足(到目前为止，只有12个菌株可从培养集合中获得)，因为在过去的十年中，分子研究一直是重点。这是对组学数据集的注释和在无菌小鼠中进行定植研究的主要限制，以测试已知具有特定特征的微生物群的因果效应，这取决于它们起源的宿主物种。为了克服这些限制，本中央项目MIMIC旨在改进在SPP 1656第一阶段进行的关于小鼠肠道细菌的分离和描述的初步工作，以提供独特和精心挑选的菌株收集。这些收集将使研究人员很容易获得细菌菌株和相应的基因组信息，但最重要的是，将作为实施一种新的生物信息学工具(MIMIC)的基础，该工具用于自动化设计最小微生物联合体，适合感兴趣的小鼠模型的个别实验设计。最小联合体的设计将以元基因组复盖战略为基础，并将嵌入新建立的生物信息学平台IMNGS进行传播(www.imngs.org)。考虑到小鼠设施之间已知的表型差异，一种创新的方法允许基于本地生态系统的可培养部分生成定制的最小细菌联合体，这与小鼠模型的标准化和细菌-细菌以及细菌-宿主相互作用的机制理解高度相关。MIMIC项目完全符合该领域和SPP 1656的当前需求。它通过与合作伙伴的多重互动嵌入到联合体活动中，例如，从不同的设施获得分离细菌的材料，获得需要适当描述的已经分离的菌株，以及在SPP 1656中产生适应当前需求的最小联合体。总而言之，目前的模拟提案是一个独特的机会，可以使用基于互补培养和分子的方法来发现新的细菌多样性，并为优先计划和更广泛的科学界创造和提供有用的资源。DFG的资金将使初步活动建立在坚实的基础上，并将国际公认的生物资源中心(DSMZ)整合到关于微生物-宿主相互作用的SPP活动中。

The gut microbiota is very important for mammalian host physiology. It is thus crucial to put effort into understanding its structure and functions. Omics technologies have generated major breakthroughs in microbiome research, but they only show correlations. To test causal relationships and to study molecular mechanisms, mouse models, have been extensively used in many research projects worldwide and within SPP 1656. However, there is an obvious deficit of bacterial strains and genomes from the mouse gut microbiome (only 12 strains are available to date from culture collections), because emphasis has been put on molecular studies over the last decade. This is a major limitation for annotation of omics datasets and for colonization studies in germfree mice to test causal effects of microbiomes known to have specific features depending on their host species of origin. To overcome these limitations, the present central project MIMIC aims at improving preliminary work performed during phase 1 of SPP 1656 on the isolation and description of mouse gut bacteria to deliver a unique and well-curated strain collection. The collection will give researchers easy access to bacterial strains and corresponding genomic information, but most of all will serve as a foundation to implement a new bioinformatics tool (MIMIC) for automated design of minimal microbial consortia adapted to individual experimental designs in mouse models of interest. The design of minimal consortia will be based on metagenomic coverage strategies and will be embedded into the newly established bioinformatic platform IMNGS for dissemination (www.imngs.org). Considering known phenotype variability between mouse facilities, an innovative approach that allows generation of customized minimal consortia of bacteria based on the cultivable fraction of native ecosystems is highly relevant regarding standardization of mouse models and mechanistic understanding of bacteria-bacteria and bacteria-host interactions. The MIMIC project is a perfect match to current needs in the field and within SPP 1656. It is embedded in the consortium activities via multiple interactions with partners, e.g., to obtain materials from different facilities for isolation of bacteria, to gain access to already isolated strains that require proper description, and to generate minimal consortia adapted to current needs within SPP 1656. In summary, the present MIMIC proposal is a unique opportunity to use complementarity culture-based and molecular approaches to discover novel bacterial diversity and to create and deliver useful resources to the priority program and more generally to the scientific community. Funding by the DFG will allow putting preliminary activities on a solid basis and integrating an internationally recognized bioresource center (the DSMZ) to SPP activities on microbe-host interactions.