Development of an improved SMALP toolkit to extract active membrane proteins

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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.