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Defining the role of myosin motor proteins and their cargo adaptors in cytokine secretion

定义肌球蛋白运动蛋白及其货物接头在细胞因子分泌中的作用

基本信息

批准号：
BB/R001316/1
负责人：
Folma Buss
金额：
$ 47.23万
依托单位：
University of Cambridge
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2018
资助国家：
英国
起止时间：
2018 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FR001316%2F1
关键词：
Defining role myosin motor proteins

项目摘要

Inflammation is the body's first line of defense to injury and infection. Cells under attack alert the immune system through the release of chemicals,called cytokines, which activate immune cells to clear the wound from bacteria and heal the tissue. However, under certain conditions the body stays on high alert and the inflammation becomes uncontrolled and chronic. Human aging is characterized by a chronic, low-grade inflammation, and this phenomenon has been termed as "inflammaging", which is a highly significant risk factor for both morbidity and mortality in elderly people, as most if not all age-related diseases share an inflammatory pathogenesis. Thus it is very important to control chronic inflammation and regulate the level of cytokines in our body to ensure healthy ageing. In this study we will investigate the machinery in cells that controls the release of cytokines. The biological cell resembles a miniature factory containing a vast collection of dedicated protein machines. These machines are driven by chemical energy and perform a huge variety of different tasks. For example highly specialysed motor proteins can translocate along filament tracks in a step-by-step motion powered by chemical energy derived from ATP. These motor proteins move cargo between different locations rather like a train running along a railway network to their specific destinations. These nanoscale motors also transport cytokines from their production sites to the cell surface, where they are released. Thus our major aim is to identify drugs that regulate these motors and thereby modify transport and release of cellular cytokines.

炎症是身体抵御损伤和感染的第一道防线。受到攻击的细胞通过释放称为细胞因子的化学物质来警告免疫系统，这些化学物质激活免疫细胞以清除伤口上的细菌并愈合组织。然而，在某些情况下，身体保持高度警惕，炎症变得不受控制和慢性。人类衰老的特征在于慢性、低度炎症，并且这种现象被称为“炎症”，这是老年人发病率和死亡率的高度显著的风险因素，因为大多数（如果不是所有的话）与年龄相关的疾病共享炎症发病机制。因此，控制慢性炎症和调节我们体内细胞因子的水平以确保健康衰老是非常重要的。在这项研究中，我们将调查机制的细胞，控制细胞因子的释放。生物细胞就像一个微型工厂，里面有大量专门的蛋白质机器。这些机器由化学能驱动，执行各种不同的任务。例如，高度特异性的马达蛋白可以在ATP产生的化学能的驱动下，沿着沿着纤维轨迹一步一步地移动。这些马达蛋白在不同的地点之间移动货物，就像火车沿着沿着的铁路网行驶到特定的目的地一样。这些纳米级马达还将细胞因子从其产生部位运输到细胞表面，在那里它们被释放。因此，我们的主要目标是确定药物，调节这些电机，从而修改运输和释放的细胞因子。