Uncovering microbial modulators of neuroactive molecules

发现神经活性分子的微生物调节剂

• 批准号: 9277190
• 负责人: Elaine Hsiao
• 金额: $ 37.27万
• 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/9277190
• 关键词: Uncovering; microbial; modulators; neuroactive; molecules

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）：人类被多种微生物群落殖民，共同称为Comensal Microbiota，这会影响广泛的生物学过程。最近的研究表明，除了几种复杂的宿主行为外，共生菌群除了在营养，免疫和代谢中的作用外，在神经系统的发展和功能中还具有基本作用。提出的研究培训计划旨在揭示特定的共生微生物与神经系统之间相互作用的基础机制，并阐明这些关系对宿主生理的影响。具体而言，拟议的研究将研究共生微生物对宿主5-羟色胺（5-羟基patmine，5-HT）代谢的作用，其目的是定义5-HT途径的特定步骤，这些步骤受到相关微生物的影响，并识别这些微生物的症状，并鉴定出对宿主5-HT的特定模型，并在5-HT上施加了AMEL OMEL OMEL OMEL OMEL OF AMEL OF AMEL OF AMEL OF AMEL OF AMEL OF AMEL OF AMEL OF AMEL OF AMEL OF AMEL OF AMEL OF AMEL OF AMEL OF AMEL构成。 5-HT相关疾病。这些研究的发现将提高我们对共生微生物如何影响健康和疾病的最新理解，并将进一步探索开发基于微生物的新型疗法的创新前景，这些疗法可以很容易地修改以获得更好的功能，调节性控制，靶向和递送。对年龄微生物群和神经系统之间相互作用的拟议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，而且还整合了生物化学（在5-HT途径中的分子变化中解剖），化学工程（用于培养的培养型和培养较高的培养物质，用于培养的较高的型号，用于培养较高的启动，以培养较高的启动，以培养较高的构造，以培养较高的构造，以培养较高的构造源源菌。微生物组），分子和行为神经科学（在羟色胺缺乏性小鼠模型中看到的病理学研究）。我提出的培训将跨越加利福尼亚理工学院的高级研究员五年独立研究。该标题通常保留给具有先前博士后经验的个人，并作为前进到初级教师职位的过渡阶段。授予该奖项大约一年后；我将招募一名全职技术员，并在实验室研究方面拥有丰富的经验。我还将通过Caltech的夏季研究计划开始指导多达两名生物学或化学本科生。