Uncovering microbial modulators of neuroactive molecules

发现神经活性分子的微生物调节剂

• 批准号: 9135979
• 负责人: Elaine Hsiao
• 金额: $ 36.31万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9135979
• 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; 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; microbiota; microorganism; mouse model; nanofabrication; nervous system disorder; novel; nutrition; open source; programs; reduce symptoms; relating to nervous system; restoration; screening; summer research; 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（由申请人提供）：人类定植有不同的微生物群落，统称为肠道微生物群，影响广泛的生物过程。最近的研究表明，除了在营养，免疫和代谢中的作用外，肠道微生物群还在神经系统的发育和功能中起着重要作用，此外还有几种复杂的宿主行为。拟议的研究培训计划旨在揭示特定肠道微生物与神经系统之间相互作用的机制，并阐明这些关系对宿主生理学的影响。具体而言，拟议的研究将检查肠道微生物对宿主5-羟色胺（5-羟色胺，5-HT）代谢的作用，旨在确定肠道微生物影响的5-HT途径的具体步骤，确定影响宿主5-HT的特定微生物物种和因素，并将这些微生物5-HT调节剂应用于改善5-HT相关疾病模型中的症状。这些研究的发现将推进我们目前对肠道微生物群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，以实现更好的功能，调节控制，靶向和递送。神经微生物群与神经系统之间相互作用的研究填补了一个新的多学科研究领域，不仅整合了神经生物学和微生物学，而且还整合了生物化学（在5-HT途径中的分子改变的解剖中），化学工程（在用于高通量限制的微流体装置的纳米芯片中，微生物组的内源性物种的培养和功能筛选）以及分子和行为神经科学（在研究在马克隆宁缺乏的小鼠模型中观察到的病理学中）。我所建议的培训将跨越五年的独立研究作为一个高级研究员在加州理工学院。这个头衔通常保留给有博士后经验的人，并作为进入初级教师职位的过渡阶段。大约一年后，我将招聘一名全职技术人员，他必须在实验室研究方面有丰富的经验。我还将开始通过加州理工学院的暑期研究项目，每年指导两名生物或化学本科生。