Defining the functional surface proteome of extracellular vesicles

定义细胞外囊泡的功能表面蛋白质组

• 批准号: 2431818
• 金额: --
• 依托单位: Aston University
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2431818
• 关键词: Defining; functional; surface; proteome; extracellular

As cells die in vivo they are removed by phagocytes in a process that resolves inflammation and prevents disease. For clearance of dying (apoptotic) cells to be efficient and timely, dying cells release extracellular vesicles (EV) to attract phagocytes to sites of cell death. Crucially, this interaction of EV with the immune system underpins the control of inflammation, a process central to health, regenerative medicine and many important inflammatory diseases.This project will define the surface proteome of extracellular vesicles across the entire size range of EV generated from dying cells. This novel approach will then help identify the factors that are essential for EV control of inflammation. EV surface proteome will be linked to function as we address the following key questions: what are the key components of EV that enable communication with the immune system? Do EV of differing sizes and sources interact in a similar manner with the immune system? Is it possible to produce a synthetic EV with a defined surface proteome to act as a mimic of EV function?Analysis of EV is a significant challenge due to EV heterogeneity. In particular, EV vary greatly in size (<50nm to >1000nm). Analysis of the smallest EV, namely exosomes, proves most challenging given existing technologies are often not sensitive enough to detect them (such as dynamic light scattering and nanoparticle tracking analysis). NanoFCM have developed a novel platform that brings together the power of flow cytometry with high sensitivity (40-50nm) for interrogation of nanoparticles. This will enable comprehensive single-EV analysis and phenotyping, providing new insight into the often difficult to detect exosome populations. Through collaboration between Aston University and NanoFCM, the EV surface will be probed at high resolution to establish a fundamental atlas of the surface proteome of EV.

当细胞在体内死亡时，它们被吞噬细胞清除，从而解决炎症并预防疾病。为了有效和及时地清除垂死（凋亡）细胞，垂死细胞释放细胞外囊泡（EV）以将吞噬细胞吸引到细胞死亡部位。最重要的是，EV与免疫系统的这种相互作用是控制炎症的基础，炎症是健康、再生医学和许多重要炎症性疾病的核心过程。该项目将定义死亡细胞产生的EV整个大小范围内的细胞外囊泡的表面蛋白质组。这种新方法将有助于确定EV控制炎症所必需的因素。EV表面蛋白质组将与功能联系起来，因为我们解决了以下关键问题：EV的关键组成部分是什么？不同大小和来源的EV是否以类似的方式与免疫系统相互作用？是否有可能产生一种具有确定表面蛋白质组的合成EV，以模拟EV功能？由于EV的异质性，EV的分析是一个重大挑战。特别地，EV在尺寸上变化很大（<50nm to >1000 nm）。对最小的EV（即外来体）的分析证明最具挑战性，因为现有技术通常不足以检测它们（如动态光散射和纳米颗粒跟踪分析）。NanoFCM开发了一种新的平台，将流式细胞术的力量与高灵敏度（40- 50 nm）结合起来，用于纳米颗粒的询问。这将实现全面的单EV分析和表型分析，为通常难以检测的外泌体群体提供新的见解。通过阿斯顿大学和NanoFCM之间的合作，EV表面将以高分辨率进行探测，以建立EV表面蛋白质组的基础图谱。