Uncovering microbial modulators of neuroactive molecules as novel therapeutics.

发现神经活性分子的微生物调节剂作为新型疗法。

• 批准号: 8610038
• 负责人: Elaine Hsiao
• 金额: $ 37.14万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-19 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8610038
• 关键词: Adverse effects; Affect; Area; Award; Behavior; Behavioral; Biochemistry; Biological Process; Biology; Brain; California; Cells; Chemical Engineering; Chemistry; Colon; Complex; Data Set; Development; Disease; Dissection; Enabling Factors; Enzymes; Eukaryotic Cell; Exhibits; Faculty; Genomics; Goals; Health; Human; Immunity; Individual; Institutes; Interdisciplinary Study; Investigation; Laboratory Research; Mediating; Mentors; Metabolism; Microbe; Microbiology; Microfluidic Microchips; Microfluidics; Mining; Modeling; Modification; Molecular; Mus; Nervous System Physiology; Nervous system structure; Neurobiology; Neurologic; Neurosciences; Neurotransmitters; Pathology; Pathway interactions; Peripheral Nervous System; Phenotype; Physiology; Play; Positioning Attribute; Postdoctoral Fellow; Property; Recruitment Activity; Research; Research Training; Role; Scientist; Serotonin; Serotonin Agents; Signal Transduction; Staging; Symptoms; Technology; Testing; Therapeutic; Time; Training; Training Programs; base; cell type; commensal microbes; experience; gut microbiota; innovation; insight; loss of function; metabolomics; microbial; microbial community; microbiome; microorganism; mouse model; nanofabrication; nervous system disorder; novel; novel therapeutics; nutrition; open source; programs; public health relevance; relating to nervous system; restoration; screening; targeted delivery; transcriptomics; transmission process; undergraduate student

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.

项目总结/摘要 人类是殖民地与不同的微生物群落，统称为细菌 微生物群，影响广泛的生物过程。最近的研究表明，除了 除了在营养、免疫和新陈代谢方面的作用外，肠道微生物群还在以下方面发挥着重要作用： 神经系统的发育和功能，以及几种复杂的宿主行为。的 拟议的研究培训计划旨在揭示相互作用的机制， 特定的肠道微生物和神经系统，并阐明这些关系对 寄主生理学具体来说，拟议的研究将研究肠道微生物对宿主的作用， 5-羟色胺（5-羟色胺，5-HT）代谢，旨在确定5-HT途径的具体步骤 确定特定的微生物种类和影响宿主的因素 5-HT，并将这些微生物5-HT调节剂应用于改善5-HT相关的模型中的症状 疾病这些研究的发现将促进我们目前对肠道微生物群如何 影响健康和疾病，并将进一步探索开发新的，基于微生物的创新前景 治疗药物，可以很容易地进行修饰以获得更好的功能、调节控制、靶向和递送。 关于肠道微生物群与神经系统之间相互作用的拟议研究填补了一个空白。 一个多学科研究的新领域，不仅整合了神经生物学和微生物学， 生物化学（在5-HT途径中的分子改变的解剖），化学工程（在 用于高通量限制、培养和功能筛选的微流体装置的纳米结构 微生物组的内源性物种）以及分子和行为神经科学（在研究 在胡萝卜素缺乏的小鼠模型中观察到的病理学）。 我建议的培训将跨越五年的独立研究作为高级研究员在 加州理工学院。这个头衔通常保留给以前有博士后经历的人。 经验，并作为一个过渡阶段推进到初级教师的位置。约 授予该奖项一年后，我将招聘一名具有丰富经验的全职技术人员 在实验室研究中。我还将开始指导多达两个生物或化学本科生， 通过加州理工学院的夏季研究计划完成一年。