Uncovering microbial modulators of neuroactive molecules as novel therapeutics.

项目摘要/摘要 人类定居于不同的微生物群落，统称为共生 微生物区系，影响一系列广泛的生物过程。最近的研究表明，除了 它们在营养、免疫和新陈代谢中的作用，共生微生物区系也在 神经系统的发育和功能，以及几种复杂的宿主行为。这个 拟议的研究培训计划旨在揭示 特定的共生微生物和神经系统，并阐明这些关系对 寄主生理学。具体地说，拟议的研究将检查共生微生物对宿主的作用。 5-羟色胺(5-羟色胺，5-羟色胺)代谢，旨在确定5-羟色胺途径的具体步骤 受共生微生物影响，确定特定的微生物种类和影响宿主的因素 5-羟色胺，并将这些微生物5-羟色胺调节剂用于改善5-羟色胺相关模型的症状 疾病。这些研究的发现将推动我们目前对共生微生物区系如何 影响健康和疾病，并将进一步探索开发新的、以微生物为基础的创新前景 治疗，可以很容易地进行修改，以实现更好的功能、调节控制、靶向和递送。 提出的关于共生微生物区系与神经系统之间相互作用的研究填补了 多学科研究的新领域，不仅整合了神经生物学和微生物学，而且还 生物化学(解剖5-羟色胺途径中的分子变化)、化学工程(在 用于高通量限制、培养和功能筛选的微流控器件的纳米制造 微生物组的内源物种)和分子和行为神经科学(在 在5-羟色胺缺乏的小鼠模型中看到的病理学)。 我提议的培训将包括五年的独立研究，作为 加州理工学院。这个头衔通常是为以前有博士后经历的个人保留的 经验，并作为一个过渡阶段，晋升到初级教员的职位。大致 获奖一年后，我将招聘一名具有丰富经验的全职技术员 在实验室研究中。我还将开始指导每名最多两名生物或化学本科生 通过加州理工学院的暑期研究项目。

PROJECT SUMMARY/ABSTRACT Humans are colonized with diverse microbial communities, collectively called the commensal microbiota, that influence a wide array of biological processes. Recent studies demonstrate that in addition to their roles in nutrition, immunity and metabolism, the commensal microbiota also plays a fundamental role in the development and function of the nervous system, in addition to several complex host behaviors. The proposed research training program aims to uncover the mechanisms underlying the interaction between specific commensal microbes and the nervous system, and to elucidate the impact of these relationships on host physiology. Specifically, the proposed research will examine the role of commensal microbes on host serotonin (5-hydroxytrypatmine, 5-HT) metabolism, with aims to define the specific steps of the 5-HT pathway that are affected by commensal microbes, identify the particular microbial species and factors that affect host 5-HT, and apply these microbial 5-HT modulators toward ameliorating symptoms in models of 5-HT-related disease. Findings from these studies will advance our current understanding of how the commensal microbiota affects health and disease, and will further explore the innovative prospect of developing novel, microbe-based therapeutics, which can be readily modified for better function, regulatory control, targeting and delivery. The proposed studies on the interaction between the commensal microbiota and nervous system fills a novel area of multidisciplinary research that integrates not only neurobiology and microbiology, but also biochemistry (in the dissection of molecular alterations in the 5-HT pathway), chemical engineering (in the nanofabrication of microfluidic devices for high-throughput confinement, cultivation and functional screening of endogenous species of the microbiome) and molecular and behavioral neuroscience (in the investigation of pathologies seen in mouse models of serotonin-deficiency). My proposed training will span five years of independent research as a Senior Research Fellow at the California Institute of Technology. This title is typically reserved for individuals with previous post-doctoral experience and serves as a transitional stage toward advancing into a junior faculty position. Approximately one year after the award is conferred, I will recruit one full-time technician, with significant previous experience in laboratory research. I will also begin mentoring up to two biology or chemistry undergraduate students per year through Caltech's summer research program.