Causes and consequences of interpersonal microbial variation

摘要 这项提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。尽管肠道微生物群可能代表一种 人类生物学的关键和容易修改的组成部分，肠道微生物区系对 健康、疾病风险和对治疗的反应在很大程度上仍然不确定。该计划的总体目标 家长助学金是理解塑造互动关系的原则、机制和过程 肠道微生物群落和它们的宿主之间。我们的策略是将厌氧微生物 诺生菌(无菌和无菌)小鼠的遗传学和高通量质谱学 模型来剖析这些相互作用。灵生小鼠是我们的中心实验系统 用来进行这些研究。这些动物被保存在无菌的柔性塑料中 隔离器或单独通风的笼子，没有任何细菌或其他微生物。然后他们就可以成为 与携带正常微生物组的传统动物相比，或与个体 细菌物种，这些物种的突变体，或以其他方式在基因中 表情是可以精确控制的。尽管我们在这个项目上取得了重大进展 论文由GM118159支持)，主要限制是我们对蒸汽灭菌器的访问受到限制 (高压灭菌器)用于准备每个实验的设备。这一限制也降低了我们的 能够与大学中由NIGMS资助的多名研究人员进行合作 请为此应用程序提供支持函。出于这些原因，我们请求资金部分支持 为灵知生菌购买蒸汽灭菌器。这个项目的成本也在显著增加 得到了大学的支持。

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.