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

我在研究中使用的微小蠕虫(线虫)的肌肉是人类肌肉的一个出人意料的好模型。它可以更容易地研究，并在许多人类不可能的实验情况下进行。目前，我们不知道是什么导致人们肌肉萎缩，这是一个影响老年人和脊柱损伤等人的问题。我之前的蠕虫研究可能提供了一些线索，其他人正在将我的结果应用到人类研究中。肌肉萎缩是对太空飞行和制动的反应。我发现在蠕虫体内，有一种特殊的蛋白质复合体(称为致密小体？以及将蠕虫肌肉附着在骨骼上的数量)在航天飞行后减少。我在地球上的实验表明，减少这些蛋白质会导致肌肉组织崩溃。我所在大学的其他人发现，石膏固定后，人类灶性粘连中的一种蛋白质减少了。此外，局灶性粘连的突变会导致四肢Girdle肌营养不良。在蠕虫致密小体和人类灶性粘连中也发现了相同的蛋白质。因此，在蠕虫和人类的附着复合体中也观察到了类似的变化，这些变化导致了蠕虫肌肉的损耗。我们目前还不知道控制和调节因素是什么，如果这些因素也调节人类肌肉消耗，也不知道不同临床人群(例如创伤患者、烧伤患者、卧床患者、老年人)之间的差异。我想回答这些问题。我现在想了解一种控制蠕虫浪费的机制。最终目标是了解人类体内所有调节消耗的机制。我觉得，一旦我们这样做了，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(S)。我希望，通过首先了解在一个简单的有机体中对浪费的调节和处理，我们可以更快、更经济地证明在人类中同样的过程的存在和处理。我还将继续努力，将结果直接传达给公众。在过去，这包括在网上免费提供结果，向公众提供免费演讲，积极让学童参与我的研究，以及通过来自世界各地的记者和广播电视主持人(在英国，包括BBC、探索频道、CNN和所有？线？)交流我的工作。向报纸提供报道的服务)。

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).