A genetic model for understanding the regulation of muscle protein degradation by muscle attachment

用于了解肌肉附着调节肌肉蛋白降解的遗传模型

• 批准号: G0801271/1
• 负责人: Nathaniel Szewczyk
• 金额: $ 55.95万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0801271%2F1
• 关键词: genetic; model; understanding; regulation; muscle

The muscle of the tiny worm I use in my studies (C. elegans) is a surprisingly good model for muscles in human beings. It can be studied more easily and in many experimental situations that are impossible in people. At the moment, we do not understand what causes muscle wasting in people, a problem that affects the elderly and those with spinal injuries among others. My previous worm studies may offer some clues, others are applying my results to studies in human beings. Muscle wasting occurs in response to spaceflight and immobilization. I discovered that in worms, a special complex of proteins (known as ?dense bodies? and which attach worm muscle to skeleton) were decreased after spaceflight. My experiments on Earth show that reducing these proteins causes muscle tissue breakdown. Others at my University found that a protein in human focal adhesions is decreased following cast immobilization. Additionally, mutations in focal adhesions cause Limb Girdle Muscular Dystrophies. The same proteins are found in worm dense bodies and human focal adhesions. Thus, similar changes are observed in worm and human attachment complexes and these changes cause worm muscle wasting. We currently have no idea what the controlling and mediating factor are, if these factors also regulate human muscle wasting, nor if they differ among various clinical populations displaying wasting (e.g. trauma patients, burn patients, bed ridden patients, the elderly). I want to answer these questions. I currently want to understand one mechanism regulating wasting in worms. The ultimate goal is understanding all of the mechanisms regulating wasting in human beings. I feel that once we do, we can understand the differences between patients and identify drug targets providing appropriate treatment(s) to each group of patients. It is my hope that by first gaining an understanding of the regulation and treatment of wasting in a simple organism, we can more rapidly and cost effectively demonstrate the existence and treatment of the same processes in people. I will also continue my efforts of communicating results directly to the public. In the past this has included making results freely available on-line, giving free talks to the public, actively engaging school children in my research, and communicating my work via reporters and radio and television presenters from around the world (in the UK these include the BBC, the Discovery Channel, CNN, and all of the ?wire? services that provide stories to newspapers).

我在研究中使用的小蠕虫的肌肉（C。elegans）是人类肌肉的一个令人惊讶的好模型。它可以更容易地进行研究，并且可以在许多人类不可能的实验情况下进行研究。目前，我们还不知道是什么原因导致人们肌肉萎缩，这是一个影响老年人和脊柱损伤的问题。我以前的蠕虫研究可能会提供一些线索，其他人正在将我的结果应用于人类的研究。 肌肉萎缩是对太空飞行和固定的反应。我发现，在蠕虫中，一种特殊的蛋白质复合物（称为？高密度的尸体以及将蠕虫肌肉附着到骨骼上的细胞）在太空飞行后减少。我在地球上的实验表明，减少这些蛋白质会导致肌肉组织分解。我所在大学的其他研究人员发现，在石膏固定后，人类局灶性粘连中的一种蛋白质减少了。此外，局灶性粘连的突变导致肢带肌营养不良。在蠕虫致密体和人类局灶性粘连中发现了相同的蛋白质。因此，在蠕虫和人类附着复合体中观察到类似的变化，这些变化导致蠕虫肌肉萎缩。我们目前不知道控制和介导因素是什么，如果这些因素也调节人类肌肉萎缩，也不知道它们在显示萎缩的各种临床人群（例如创伤患者，烧伤患者，卧床患者，老年人）中是否存在差异。我想回答这些问题。我现在想了解一种调节蠕虫消耗的机制。最终的目标是了解所有调节人类浪费的机制。我认为，一旦我们这样做，我们就可以了解患者之间的差异，并确定药物靶点，为每一组患者提供适当的治疗。我希望，通过首先了解简单生物体中浪费的调节和治疗，我们可以更快，更经济地证明人类中相同过程的存在和治疗。我还将继续努力，直接向公众宣传结果。在过去，这包括在网上免费提供结果，向公众提供免费演讲，积极吸引学生参与我的研究，并通过来自世界各地的记者和广播电视主持人（在英国，这些包括BBC，探索频道，CNN，以及所有的？电线？为报纸提供新闻的服务）。