Development of an improved SMALP toolkit to extract active membrane proteins

生命依赖于我们体内由蛋白质组成的微小机器。这些机器具有广泛的功能，从消化我们的食物，到保护我们免受感染，再到让我们看到东西。最重要的一类蛋白质机器是那些生活在细胞周围膜上的蛋白质机器。这些膜蛋白允许营养物质进入细胞并允许废物离开；它们还调节信号进出细胞的运动。这些功能使研究人员对它们特别感兴趣，但也许更重要的是，它们也是开发植物和动物健康新疗法的最重要目标。例如，今天使用的所有药物中有50%以上是针对这些膜蛋白的。不幸的是，这些蛋白质被证明是非常难以研究的，并且在过去的50年里让大量的科学家感到困惑。2009年，我们发现了一种全新的方法，通过使用一种简单的聚合物来制造这些蛋白质，这种聚合物在汽车仪表板和油漆中更常见。这种方法将蛋白质“包裹”在一个保护性的聚合物“带”中，使其保持稳定，使我们能够研究它。这种新方法为科学家们研究这些重要的蛋白质开辟了一系列新的机会。这其中包括制药公司的科学家们的极大兴趣，他们发现这种方法使他们更容易开发新药。然而，与任何方法一样，我们的方法有一些小而重要的局限性，这意味着它目前不能用于研究这些蛋白质机器如何工作的所有方面。例如，我们的方法可以防止这些蛋白质改变形状。这种变化通常对蛋白质的功能很重要。你可以说聚合物带弹性不够！在这个项目中，我们的目标是开发一种新的改进的“工具包”，其中包含新的聚合物和新的方法，我们希望这些方法能够使这些蛋白质得到研究。我们希望首先与学术科学家合作，以确保这些方法适用于生活中遇到的最重要的蛋白质家族。然后，我们将扩大我们的合作，以包括商业科学家，确保在开发新药和农用化学品方面继续取得快速进展。

Life depends on tiny machines within our bodies made from protein. These machines have a wide range of functions from digesting our food, through to defending us from infection and allowing us to see. One of most important classes of protein machines is those that live in the membrane that surround cells. These membrane proteins allow nutrients into the cell and allow waste products to leave; they also mediate the movement of signals into and out of the cell. These functions make them exceptionally interesting to researchers, but perhaps more importantly they are also the most important targets for developing new therapeutics for plant and animal health. For example more than 50% of all drugs used today target these membrane proteins. Unfortunately these proteins have proved to be exceptionally difficult to study and have confounded a large number of scientists over the past 50 years. In 2009 we found an entirely new way of making these proteins by using a simple polymer more commonly found in car dashboards and paint. This method "wraps" the protein in a protective polymer "belt" that keeps it stable allowing us to study it. This new method has opened up a whole range of new opportunities for scientists to study these important proteins. This has included significant interest from scientists in pharmaceutical companies who have found that the method makes it a lot easier for them to develop new drugs. However as with any method, our method has some small but significant limitations that mean that it cannot currently be used to study all aspects of how these protein machines work. For example our method prevents these proteins from changing shape. Such changes are often important for the function of the protein. You could say that the polymer belt is not elastic enough! In this project we aim to develop a new improved "tool kit" that contains new polymers and new methods that we hope will allow these proteins to be studied. We are hoping to first work with academic scientists to ensure that the methods work with the most important families of proteins encountered in life. We will then extend our collaborations to encompass commercial scientists ensuring that progress in developing new drugs and agrochemicals continues at a rapid rate.