Center of Biomedical Research Excellence in CNS Metabolism

中枢神经系统(CNS)的新陈代谢和神经元兴奋性是相互依赖的，因此CNS 新陈代谢是认知、记忆和行为的生化基础。中枢神经系统调节失调与 许多疾病，包括阿尔茨海默氏症、癫痫、帕金森氏症和脑损伤，但 中枢神经系统代谢和疾病之间的机制联系还知之甚少。伊利诺伊大学 肯塔基(英国)医学院在过去几年中对研究人员进行了重大投资 拥有代谢和代谢组学专业知识和仪器来支持他们的研究工作，这已经 增强在神经科学、癌症、心血管疾病、糖尿病和肥胖研究方面的现有优势。 因此，英国建议建立一个独特的多学科生物医学研究卓越中心(COBRE) 论CNS代谢(CNS-Met)作为一个战略设计的、可持续的、促进前沿的框架 研究的重点是大脑功能和疾病的代谢介质的作用。建议数 跨学科中心利用在葡萄糖生物学、神经信号转导、 线粒体新陈代谢、系统神经科学和数据科学，以及高级 代谢组学和成像能力，以创建以中枢神经系统为重点的综合研究框架 新陈代谢。其首要目标是通过提供一个 以主题为重点的可持续多学科基础设施，致力于定义 代谢到中枢神经系统功能和神经疾病，并利用这一新平台开发前景广阔的 在一个令人兴奋和有影响力的中枢神经系统研究领域，拥有高技能的早期调查人员。要完成 为了实现这些目标，我们将实现四个具体目标：(1)培养足够数量的有研究经费的调查人员 与科布雷的统一主题直接相关的计划；(2)提供强大的基于团队的指导组合 基础和临床专业知识；(3)招募神经病学多学科领域的新研究人员 通过试点项目拨款和招募初级研究项目负责人来实现功能障碍；以及(4)创建 通过与英国强大的研究中心和核心设施的关键链接，实现研究项目之间的协同，包括 现有的科布雷。新出现的协同效应将通过三个研究项目来发展，一个行政项目 核心，代谢组学的关键研究核心，都通过强大的生物统计/生物信息学支持联系在一起，所有 这对拟议的研究至关重要，并将有助于机构资源的开发。这个 这三个研究项目的科学重点是大脑代谢与神经疾病的相互作用， 跨越基本视角和翻译视角。这种多学科专业知识的集中集中在 被广泛认识但未被充分研究的神经系统疾病的代谢机制有望取得重大的新进展 对中枢神经系统代谢的整体认识。CNS-Met将创造一大批熟练的科学家 都做好了充分的准备，可以领导一个专注于未来中枢神经系统代谢的可持续研究中心。

Central nervous system (CNS) metabolism and neuronal excitability are interdependent, and so CNS metabolism is the biochemical basis of cognition, memory, and behavior. Dysregulation of CNS is implicated in numerous disorders, including Alzheimer’s Disease, epilepsy, Parkinson’s disease, and brain injury, but the mechanistic connections between CNS metabolism and disease are poorly understood. The University of Kentucky (UK) College of Medicine has made significant investments over the last few years in investigators with metabolic and metabolomics expertise and instrumentation to support their research efforts, which has enhanced existing strengths in neuroscience, cancer, cardiovascular, and diabetes and obesity research. Thus, UK proposes to establish a unique multidisciplinary Center of Biomedical Research Excellence (COBRE) on CNS Metabolism (CNS-Met) as a strategically designed, sustainable framework that promotes leading-edge research focused on the role of metabolic mediators of brain function and disease. The proposed interdisciplinary center leverages highly specialized expertise in glucose biology, neuronal signaling, mitochondrial metabolism, systems neuroscience, and data sciences as well as the presence of advanced metabolomics and imaging capabilities to create an integrated research framework focused on CNS metabolism. The overarching goals are to strengthen UK’s neuroscience research enterprise by providing a thematically focused and sustainable multidisciplinary infrastructure dedicated to defining the contribution of metabolism to CNS function and neurological diseases and to use this novel platform to develop promising and highly-skilled, early-stage investigators in an exciting and impactful area of CNS research. To accomplish these goals, we will meet four specific aims: (1) Develop a critical mass of funded investigators with research programs directly related to the COBRE’s unifying theme; (2) provide strong team-based mentoring combining basic and clinical expertise; (3) recruit new investigators to the COBRE in multidisciplinary areas of neurologic dysfunction through pilot project grant and recruitment of junior Research Project Leaders; and (4) create synergy among research projects via critical links to strong research centers and core facilities at UK, including existing COBREs. Emerging synergies will be developed through three research projects, an Administrative Core, a critical research core in Metabolomics, all linked by strong biostatistics/bioinformatics support, all of which are critical to the proposed studies and will contribute to the development of institutional resources. The scientific focus of the three research projects are brain metabolism interactions with neurological disease, spanning basic and translational perspectives. This concentration of multidisciplinary expertise focused on widely recognized yet understudied metabolic mechanisms of neurological diseases promises significant new understandings of CNS metabolism overall. The CNS-Met will create a critical mass of skilled scientists who are well equipped to lead a sustainable research center focused on CNS metabolism into the future.