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。

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要/摘要人类被各种微生物群落殖民，共同称为Consensal 微生物群，这会影响广泛的生物学过程。最近的研究表明，除了共生微生物群在营养，免疫和代谢中的作用，在除了几种复杂的宿主行为外，神经系统的发展和功能。这拟议的研究培训计划旨在发现相互作用之间相互作用的机制特定的共生微生物和神经系统，并阐明这些关系对宿主生理学。具体而言，拟议的研究将检查共生微生物在宿主中的作用 5-羟色胺（5-羟基patmine，5-HT）代谢，目的是定义5-HT途径的特定步骤受共生微生物影响的，确定影响宿主的特定微生物物种和因素 5-HT，并将这些微生物5-HT调节剂应用于5-HT相关的模型中的改善症状疾病。这些研究的发现将提高我们目前对共生微生物群如何的理解影响健康和疾病，并将进一步探索开发基于微生物的新型的创新前景治疗剂，可以很容易地修改以获得更好的功能，调节性控制，靶向和交付。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充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，还整合了生物化学（在5-HT途径中分子改变时），化学工程（在用于高通量限制，培养和功能筛选的微流体设备的纳米机制微生物组的内源物种）和分子和行为神经科学（在研究中在5-羟色胺缺乏症的小鼠模型中看到的病理学）。我提出的培训将跨越五年的独立研究，担任高级研究员加利福尼亚理工研究所。此标题通常保留给先前博士后的人经验并成为前进到初级教师职位的过渡阶段。大约授予该奖项的一年后，我将招募一位全职技术员，并拥有以前的丰富经验在实验室研究中。我还将开始指导多达两名生物学或化学本科生通过加州理工学院的夏季研究计划的一年。