Lipidome Remodeling During Development of T1D

T1D 发展过程中的脂质组重塑

• 批准号: 10349473
• 负责人: Qibin Zhang
• 金额: $ 35.46万
• 依托单位: UNIVERSITY OF NORTH CAROLINA GREENSBORO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10349473
• 关键词: Antigens; Autoimmune Diseases; Beta Cell; Biological Process; Cell Death; Cells; Cellular Membrane; Clinical; Communities; Complement; Complex; Development; Disease; Dissociation; Etiology; Glycolipids; Glycosphingolipids; Goals; Human; Inbred NOD Mice; Insulin-Dependent Diabetes Mellitus; Isomerism; Isotope Labeling; Label; Lipids; Liquid Chromatography; Measures; Mediating; Mediator; Methods; Molecular; Organism; Ozone; Pathogenesis; Pathologic; Pattern; Peptides; Physiology; Positioning Attribute; Proteins; Protocols documentation; Recovery; Reproducibility; Research; Resolution; Resources; Role; Signal Transduction; Structure; Structure of beta Cell of islet; Symptoms; T-Lymphocyte; Techniques; Technology; Tissues; Transcript; Unsaturated Fats; Variant; Vertebral column; biological systems; human disease; human model; improved; interest; lipid mediator; lipid metabolism; lipidome; lipidomics; model organism; mouse model; pi bond; public health relevance; stable isotope; tool; two-dimensional

Project Summary/Abstract DESCRIPTION: Lipids are essential cellular components and act as mediators in cell signaling. The function of lipids is determined by their structures. Dysregulated lipid metabolism is associated with a variety of pathological conditions, including Type 1 Diabetes (T1D). The levels of lipids cannot be predicted by the transcripts or proteins. To understand more about the role of lipids in the development of T1D, an important first step is to directly measure the temporal changes of lipids in an organism that shares similar physiology with human T1D. Built on our technological advancements in comprehensive global lipidomics, targeted lipidomic analysis of lipid mediators, isobaric labeling-based multiplexed analysis of intact glycolipids and determination of C=C unsaturation in intact lipids, in this project, we aim to profile the longitudinal changes of the nonobese diabetic (NOD) mouse lipidome during different stages of T1D development by accomplishing the following: 1) in-depth profile and accurately quantify the major lipids in T1D-pertinent tissues using global lipidomics; 2) use advanced technologies to improve structural resolution, accurately identify and quantify glycolipids and broadly profile bioactive lipid mediators; and 3) compare lipid expression profiles in different tissues and characterize lipidome remodeling during different stages of T1D development. Successfully accomplishing these goals will not only provide invaluable resource to the research community interested in the role of lipids in the development of T1D, but it will also provide better practices for conducting lipidomics research in general.

项目概要/摘要 描述：脂质是重要的细胞成分，在细胞信号传导中充当介质。的功能 脂质是由其结构决定的。脂质代谢失调与多种因素有关 病理状况，包括 1 型糖尿病 (T1D)。血脂水平无法通过 转录物或蛋白质。为了更多地了解脂质在 T1D 发展中的作用，一个重要的 第一步是直接测量具有相似生理机能的生物体中脂质的时间变化 与人类 T1D。以我们在全面的全球脂质组学方面的技术进步为基础，有针对性 脂质介质的脂质组学分析、完整糖脂的基于同量异位标记的多重分析和 测定完整脂质中的 C=C 不饱和度，在这个项目中，我们的目标是描绘 通过完成 T1D 发展不同阶段的非肥胖糖尿病 (NOD) 小鼠脂质组 以下内容：1) 使用全局数据深入分析并准确量化 T1D 相关组织中的主要脂质 脂质组学； 2）利用先进技术提高结构分辨率，准确识别和量化 糖脂和广泛的生物活性脂质介质； 3）比较不同细胞中的脂质表达谱 组织并表征 T1D 发展不同阶段的脂质组重塑。成功地 实现这些目标不仅将为感兴趣的研究界提供宝贵的资源 脂质在 T1D 发展中的作用，但它也将为开展脂质组学提供更好的实践 研究一般。