Causes and consequences of interpersonal microbial variation

总结 本建议的目的是为我们目前资助的NIGMS提供设备支持 （R35GM118159）研究项目。尽管肠道微生物组可能代表了一种 肠道微生物群是人类生物学的关键和容易改变的组成部分， 健康、疾病风险和对治疗的反应在很大程度上仍不明确。的总体目标 父母补助金是为了了解形成互动的原则，机制和过程 肠道微生物群落和宿主之间的联系我们的策略是将联合收割机 用无菌（无菌和无菌）小鼠进行遗传学和高通量质谱分析 模型来剖析这些相互作用。致菌小鼠是我们的核心实验系统， 来进行这些研究。这些动物，这是保持在无菌软塑料 隔离器或单独通风的笼子，没有任何细菌或其他微生物。然后，它们可以 与携带正常微生物组的常规动物相比，或与个体微生物组一起定殖的常规动物相比， 细菌物种、这些物种的突变体或另外工程化的菌株，其中基因 可以精确控制表达。虽然我们在项目中取得了重大进展（12 GM 118159支持的论文），主要限制是我们对蒸汽灭菌器的访问受限 （高压灭菌器）用于准备每个实验的设备。这种限制也减少了我们的 能够与多个NIGMS资助的大学研究人员合作， 提供支持本申请的信件。为此，我们要求提供资金， 购买一台蒸汽灭菌器用于灭菌。该项目的成本也在大幅增加。 由大学支持。

Summary The purpose of this proposal is to provide equipment support to our currently funded NIGMS (R35GM118159) research project. Despite the possibility that the gut microbiome may represent a critical and readily modifiable component of human biology, the contribution of the gut microbiota to health, disease risk, and response to therapy remains largely undefined. The overall goal of the parent grant is to understand the principles, mechanisms, and processes that shape the interaction between gut microbial communities and their hosts. Our strategy is to combine anaerobic microbial genetics and high-throughput mass spectrometry with gnotobiotic (germfree and ex-germfree) mouse models to dissect these interactions. Gnotobiotic mice are the central experimental system that we're using to conduct these studies. These animals, which are maintained in sterile flexible plastic isolators or individually ventilated cages, lack any bacteria or other microbes. They can then be compared to conventional animals that carry a normal microbiome, or colonized with individual bacterial species, mutants of these species, or otherwise engineered strains in which gene expression can be precisely controlled. Although we have made significant progress in the project (12 papers supported by GM118159), the main limitation is our restricted access to the steam sterilizer (autoclave) equipment that is used to prepare every experiment. This limitation also reduces our ability to engage in collaborations with multiple NIGMS-funded researchers at the university who provide letters of support for this application. For these reasons, we request funds to partially support the purchase of a steam sterilizer for gnotobiotics. The cost of this project is also being significantly supported by the university.