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: 8737996
• 负责人: Elaine Hsiao
• 金额: $ 41.13万
• 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/8737996
• 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

DESCRIPTION (provided by applicant): 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.

描述(申请人提供)：人类定居于不同的微生物群落，统称为共生微生物区系，它们影响着广泛的生物过程。最近的研究表明，除了在营养、免疫和新陈代谢方面发挥作用外，共生微生物区系还在神经系统的发育和功能以及一些复杂的寄主行为中发挥着重要作用。拟议的研究培训计划旨在揭示特定共生微生物与神经系统之间相互作用的潜在机制，并阐明这些关系对宿主生理的影响。具体地说，这项拟议的研究将考察共生微生物对宿主5-羟色胺(5-羟色胺，5-HT)代谢的作用，目的是定义共生微生物影响5-HT途径的具体步骤，识别影响宿主5-HT的特定微生物种类和因素，并将这些微生物5-HT调节剂应用于改善5-HT相关疾病模型的症状。这些研究的结果将推进我们目前对共生微生物区系如何影响健康和疾病的理解，并将进一步探索开发新型微生物疗法的创新前景，这些疗法可以很容易地进行修改，以获得更好的功能、监管控制、靶向和递送。关于共生微生物群和神经系统之间相互作用的拟议研究填补了一个新的多学科研究领域，该领域不仅包括神经生物学和微生物学，而且还包括生物化学(解剖5-羟色胺途径中的分子变化)、化学工程(纳米制造用于高通量限制、培养和功能筛选微生物组内源物种的微流体装置)以及分子和行为神经科学(研究5-羟色胺缺乏的小鼠模型中的病理学)。我提议的培训将包括五年的独立研究，作为加州理工学院的高级研究员。这个头衔通常是为有博士后经验的个人保留的，是进入初级教员职位的过渡阶段。获奖大约一年后，我将招聘一名全职技术人员，具有丰富的实验室研究经验。我还将开始通过加州理工大学的暑期研究项目，每年指导最多两名生物或化学本科生。