Metabolic regulation of exosome biogenesis

外泌体生物发生的代谢调节

• 批准号: 10668526
• 负责人: Sangmoo Jeong
• 金额: $ 40.94万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10668526
• 关键词: Address; Biogenesis; Biological Markers; Blood; Brain Injuries; Cell membrane; Cell secretion; Cells; Clinical Treatment; Clinical Trials; Detection; Diagnosis; Diagnostic; Diameter; Disease; Future; Generations; Goals; Mesenchymal Stem Cells; Metabolic; Metabolism; Mitochondria; Molecular; Monitor; Natural regeneration; Nutrient; Production; Proteins; RNA; Regulation; Research; Role; Sorting; Stress; Technology; Testing; Therapeutic; Therapeutic Agents; Urine; Vesicle; cell type; clinical application; exosome; extracellular vesicles; immunoregulation; microvesicles; nanoscale

Project Summary/Abstract Exosomes are nanoscale vesicles with a diameter of 50-200 nm, actively secreted by various types of cells in our body. As they carry biomolecules (e.g., proteins, RNAs, or metabolites) specific to their parental cells and are easily found in biofluids (e.g., blood or urine), exosomes have emerged as a promising biomarker for the detection and treatment monitoring of various diseases. Also, exosomes have the strong potential as a therapeutic agent for regeneration and immune regulation; for example, exosomes from mesenchymal stem cells (MSCs) have been tested in clinical trials for the treatment of brain injury. However, the fundamental mechanisms of what makes cells secrete exosomes and how the molecular contents in exosomes are determined remain unclear; for example, we have limited information about how to regulate MSCs to maximize the production of their exosomes carrying therapeutic molecules. My Lab aims to address these questions by investigating the role of metabolism in exosome biogenesis, because multiple steps of exosome biogenesis, including vesicle formation inside a cell and fusing into the plasma membrane, are directly associated with metabolic processes. In this Project, we will investigate how the exosome generation rate and molecular contents are determined under different metabolic conditions, specifically with the modulation of nutrients and NAD levels. We will also develop a single exosome sorting technology based on intravesicular proteins and investigate the biogenesis of exosomes with mitochondrial molecules under mitochondrial stress conditions. The research accomplishments from this Project will deepen our understanding of exosomes and help us develop exosome-based diagnostic and therapeutic strategies more effectively. Our long-term research goal is to identify the mechanisms of the interplay between metabolism and biogenesis of extracellular vesicles (EVs). This MIRA research focuses on exosomes, a subpopulation of EVs. Based on our research progresses, we will expand our research scope to other EVs, including microvesicles, in the future.

项目摘要/摘要 外泌体是直径为50-200 nm的纳米级囊泡，由各种类型的细胞积极分泌 我们的身体。当它们携带生物分子（例如蛋白质，RNA或代谢产物）特有其父母细胞的生物分子和 在生物流体（例如血液或尿液）中很容易发现，外泌体已成为有希望的生物标志物 各种疾病的检测和治疗监测。而且，外泌体具有强大的潜力 再生和免疫调节的治疗剂；例如，来自间充质茎的外泌体 细胞（MSC）已在临床试验中进行了测试，以治疗脑损伤。但是，基本 使细胞分泌外泌体以及外泌体中分子含量的机制 确定尚不清楚；例如，我们有有关如何调节MSC以最大化的信息 携带治疗分子的外泌体的产生。我的实验室旨在通过 研究代谢在外泌体生物发生中的作用，因为外泌体生物发生的多个步骤 包括细胞内部的囊泡形成并融合到质膜中，与 代谢过程。在这个项目中，我们将研究外泌体生成率和分子如何 含量是在不同的代谢条件下确定的，特别是在养分的调节下确定 NAD级别。我们还将开发基于插入式蛋白质和 在线粒体应力条件下研究外泌体的生物发生。 该项目的研究成就将加深我们对外泌体的理解，并帮助我们 更有效地制定基于外部的诊断和治疗策略。我们的长期研究目标是 确定代谢与细胞外囊泡（EV）生物发生之间相互作用的机制。 这项MIRA研究的重点是外泌体，即电动汽车的亚群。根据我们的研究进展，我们将 将来将我们的研究范围扩展到其他电动汽车，包括微泡。