Washington University Chronic KidneyDisease National Resource Center

项目摘要/摘要：总体组成部分 华盛顿大学慢性肾脏疾病国家资源中心专注于 慢性肾脏病(CKD)问题，影响近15%的美国人口并携带 严重的发病率和死亡率。几项科学进步有望加速慢性肾脏病的研究， 但由于有限的专业知识，肾脏研究界无法获得这些进展中的许多 和/或需要昂贵的设备。因此，这一NRC将解决提供 更好地利用单细胞组学、遗传学和新陈代谢方面的尖端技术进行肾脏研究 社区促进CKD研究的进展。本·汉弗莱斯博士是整个项目的负责人，而这 中心将由四个核心组成：一个管理核心、两个生物医学资源核心和一个资源 开发核心。行政核心将监督资金在各核心之间的分配，沟通 与国家奥布莱恩联盟合作，管理暑期学生充实计划，并促进 早期调查人员的参与和多样化的劳动力。变体验证核心，其中一个 生物医学资源核心，研究不确定意义的遗传变异的致病性 CRISPR/Cas9-基因编辑，在电子方法中，并在体外测试中量身定做。新陈代谢核心，另一个 生物医学资源核心，为用户提供咨询和访问一系列代谢分析，以 询问与慢性肾脏病相关的肾脏代谢变化。这些检测包括海马生物通量分析， 组织体外、非靶向代谢组学和稳定同位素示踪剂的放射性底物氧化分析 学习。新陈代谢核心还将与奥布莱恩联盟合作，为 通常进行的分析(例如，原代细胞上的海马分析)，并提供动手培训使用 这些协议。单细胞基因组研究进展(SCORE)的核心是资源开发 Core，为Split Pool等尖端技术开发协议和生物信息学管道 基于空间分辨的单核多组学和高分辨率原位测序条码 转录学。所有四个核心都将与奥布莱恩国家资源中心的网络一起工作，以 使肾脏研究界更容易获得科学进步，特别强调 初级调查人员和多样化生物医学劳动力的发展。

Project Summary/Abstract: Overall Component The Washington University Chronic Kidney Disease National Resource Center is focused on the significant problem of chronic kidney disease (CKD), which affects almost 15% of the US population and carries significant morbidity and mortality. Several scientific advances have the promise to accelerate CKD research, but many of these advances are not accessible to the kidney research community due to limited expertise and/or the need for expensive equipment. Thus, this NRC will address the fundamental challenge of providing better access to cutting-edge techniques in single cell omics, genetics, and metabolism to the kidney research community to facilitate advances in CKD research. Dr. Ben Humphreys is the overall program director, and this Center will consist of four Cores: an Administrative Core, two Biomedical Resource Cores, and a Resource Development Core. The Administrative Core will oversee distribution of funds across the Cores, communicate with the National O’Brien Consortium, manage the Summer Student Enrichment Program, and promote the involvement of early stage investigators and a diverse workforce. The Variant Validation Core, one of the Biomedical Resource Cores, investigates the pathogenicity of genetic variants of uncertain significance using CRISPR/Cas9-gene editing, in silico approaches, and tailored in vitro assays. The Metabolism Core, the other Biomedical Resource Core, provides consultation for users and access to a number of metabolic assays to interrogate changes in kidney metabolism relevant to CKD. These assays include Seahorse bioflux analysis, radioactive substrate oxidation assays of tissue ex vivo, untargeted metabolomics, and stable isotope tracer studies. The Metabolism Core will also work with the O’Brien Consortium to provide validated protocols for assays commonly performed (e.g. Seahorse assays on primary cells) and provide hands’ on training using these protocols. The Single Cell Omics Research Evolution (SCORE) Core is the Resource Development Core, which develops protocols and bioinformatics pipelines for cutting-edge techniques like split pool barcoding for single nuclei multi-omics and high resolution in-situ sequencing-based spatially resolved transcriptomics. All four Cores will work together and with the network of O’Brien National Resource Centers to make scientific advancements more accessible to the kidney research community with particular emphasis on junior investigators and development of a diverse biomedical workforce.