Multi-Omics Core

多组学核心

• 批准号: 10407941
• 负责人: JUNMIN PENG
• 金额: $ 60.19万
• 依托单位: MAYO CLINIC JACKSONVILLE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10407941
• 关键词: Address; Affect; Affinity Chromatography; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Animals; Apolipoprotein E; Biological Markers; Biology; Brain; Cell model; Cells; Cerebrospinal Fluid; Chemicals; Clinical; Collaborations; Communities; Complex; Coupled; DNA; Data Set; Diagnosis; Disease; Disease Progression; Evaluation; Functional disorder; Genotype; Goals; Human; Knock-in Mouse; Label; Libraries; Link; Lipids; Mass Spectrum Analysis; Molecular; Mus; Nerve Degeneration; Organoids; Pathogenesis; Pathogenicity; Pathway interactions; Phase; Post-Translational Protein Processing; Protein Isoforms; Proteins; Proteome; Proteomics; RNA; RNA Splicing; Reagent; Research; Research Personnel; Role; Running; Sampling; Serum; Shotguns; Spliceosomes; Technology; U1 Small Nuclear Ribonucleoprotein; apolipoprotein E-4; aqueous; base; clinically relevant; disease heterogeneity; genotypic sex; human tissue; improved; innovation; lipidome; lipidomics; metabolome; metabolomics; mouse model; multidisciplinary; multiple omics; nanoscale; novel; pre-clinical; prevent; protein complex; protein metabolite; transcriptome

PROJECT SUMMARY (APOE U19 Core F: Multi-Omics Core) This Multi-Omics Core (Core F) aims to develop and apply state-of-the-art proteomics, metabolomics and lipidomics technologies to investigate the mechanisms of APOE genotype on Alzheimer’s disease (AD) risk at the molecular, cellular and pathogenic levels. Given the dysfunction of complex and synergistic pathways contributes to AD heterogeneity, identifying clinically relevant molecules (DNAs, RNAs, proteins, metabolites and lipids) is essential to predict, diagnose, treat, and prevent AD. As such, this Core seeks to develop and apply technologies based on mass spectrometry (MS), coupled with transcriptome studies, to uncover proteomic, metabolomic, and lipidomic changes. Omics assessments will be made directly using human tissues and biofluids, human organoids, mouse and cell models, as well as isolated cellular compartments and protein complexes linked to AD in an apoE isoform-dependent manner. To achieve this goal, we have assembled a strong multidisciplinary team with established and renowned investigators in proteomics (Peng), metabolomics (Peng) and lipidomics (Han), both having extensive expertise in studying neurodegeneration. The Core will apply the latest proteomics, metabolomics and lipidomics strategies across U19 components, specifically Projects 2, 3, and 4, and Cores B, C, D, E, and G; the Core will also further advance these technologies to address unmet needs of the apoE research community in the following aims: (i) develop and apply a nanoscale, 27- plex MS-based platform for analyzing apoE-related proteome, protein modifications and protein interactome; (ii) develop and apply untargeted and targeted metabolomics technologies with evaluation of false discovery rate for analyzing apoE-affected metabolome; (iii) develop and apply the lipidomics technologies to serve the apoE research community; and (iv) apply multi-omics approaches to define the effects by APOE genotype, sex, and disease status. In summary, this Core will develop and provide the cutting edge MS-based multi-omics approaches for discovering novel, crucial apoE-related molecules/ networks during aging and AD pathogenesis in this U19 application.

项目总结（APOE U19核心F：多组学核心） 该多组学核心（核心F）旨在开发和应用最先进的蛋白质组学，代谢组学和 脂质组学技术研究APOE基因型对阿尔茨海默病（AD）风险的机制， 分子、细胞和致病水平。鉴于复杂的协同途径的功能障碍 有助于AD异质性，识别临床相关分子（DNA、RNA、蛋白质、代谢物 和脂质）对于预测、诊断、治疗和预防AD是必不可少的。因此，本核心旨在开发和应用 基于质谱（MS）的技术，加上转录组研究，以揭示蛋白质组学， 代谢组学和脂质组学变化。组学评估将直接使用人体组织进行， 生物流体，人类类器官，小鼠和细胞模型，以及分离的细胞区室和蛋白质 以apoE亚型依赖性方式与AD连接的复合物。为了实现这一目标，我们组织了一个 强大的多学科团队，在蛋白质组学（Peng）、代谢组学 （Peng）和lipidomics（Han），两者都在研究神经变性方面具有广泛的专业知识。核心将适用 U19组件的最新蛋白质组学、代谢组学和脂质组学策略，特别是项目 2、3和4，以及核心B、C、D、E和G;核心还将进一步推进这些技术，以解决 载脂蛋白E研究界在以下目标中未满足的需求：（i）开发和应用纳米级，27- 用于分析apoE相关蛋白质组、蛋白质修饰和蛋白质 （二）开发和应用非靶向和靶向代谢组学技术， 分析apoE影响的代谢组的错误发现率;（iii）开发和应用脂质组学 技术服务于apoE研究界;（iv）应用多组学方法来定义 APOE基因型、性别和疾病状态的影响。总而言之，本核心将开发并提供 尖端的基于MS的多组学方法，用于发现新的、关键的apoE相关分子/ 网络在衰老和AD发病机制在这个U19应用。