Multi-Omics Core

多组学核心

• 批准号: 10667454
• 负责人: JUNMIN PENG
• 金额: $ 60.01万
• 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/10667454
• 关键词: Address; Affect; Affinity Chromatography; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Animal Model; Apolipoprotein E; Biology; Brain; Cell model; Cells; Cerebrospinal Fluid; Chemicals; Clinical; Collaborations; Communities; Complex; Coupled; DNA; Data Set; Derivation procedure; Diagnosis; Disease; Disease Progression; Evaluation; Functional disorder; Genotype; Goals; Human; Knock-in Mouse; Label; Libraries; Link; Lipids; Mass Spectrum Analysis; Methods; Molecular; Multiomic Data; Mus; Nerve Degeneration; Organoids; Pathogenesis; Pathogenicity; Pathway interactions; Phase; Phosphorylation; 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; aqueous; candidate marker; clinically relevant; disease heterogeneity; human tissue; improved; innovation; lipidome; lipidomics; metabolome; metabolomics; mouse model; multidisciplinary; multiple omics; nanoscale; novel; potential biomarker; pre-clinical; prevent; protein complex; sex; 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.

项目摘要（APOE U19核心F：多摩斯核心） 这种多摩斯核心（核心F）旨在开发和应用最先进的保护剂，代谢组学和 脂肪态学技术是为了研究阿尔茨海默氏病（AD）风险的APOE基因型的机制 分子，细胞和致病水平。鉴于复杂和协同途径的功能障碍 有助于AD异质性，鉴定临床相关的分子（DNA，RNA，蛋白质，代谢物 和脂质）对于预测，诊断，治疗和预防AD至关重要。因此，该核心试图开发和应用 基于质谱（MS）的技术，再加上转录组研究，以发现蛋白质组学， 代谢组和脂肪组学变化。 OMICS评估将直接使用人体组织和 生物流体，人体器官，小鼠和细胞模型以及分离的细胞室和蛋白质 以APOE同工型依赖性方式链接到AD的复合物。为了实现这一目标，我们组装了 强大的多学科团队，拥有既定且著名的保护性剥削研究人员（PENG），代谢组学 （PENG）和脂质组学（HAN），都在研究神经退行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 APOE研究界未满足的需求在以下目的中：（i）开发和应用纳米级，27-- 基于PLEX MS的平台，用于分析与APOE相关的蛋白质组，蛋白质修饰和蛋白质 互动组； （ii）通过评估 分析受APOE影响代谢组的错误发现率； （iii）开发和应用脂质瘤 为APOE研究社区服务的技术； （iv）采用多摩学方法来定义 APOE基因型，性别和疾病状况的影响。总而言之，该核心将发展并提供 最先进的基于MS的多词方法，用于发现新型的，至关重要的APOE相关分子/ 在此U19应用中，衰老和AD发病机理期间的网络。