Folding and stability of the beta adrenergic receptor

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Proteins are the 'worker molecules' in life. Cells in our bodies sense and communicate with the outside world via proteins embedded in membranes that surround the cells. This project aims to design a new method to study a particular type of protein, membrane proteins. In particular, it is focussed on a protein that acts as a receptor during communication between cells. This receptor is a member of the largest family of membrane proteins in the human genome, a family that is the major target for the development of new medicines. Unfortunately, there is a limited understanding of how these membrane receptor proteins work at a molecular level. This is because they are notoriously unstable outside the membrane and it is difficult to obtain sufficient amounts for scientific study. Recent advances are, however, beginning to alter this situation. We aim to devise new methods to study a phenomenon known as 'folding'. Genes carry the code for proteins, but puzzles remain in deciphering how genetic information is translated into functional proteins. Proteins begin as a string of amino acids, which then have to fold-up to a particular shape in the right part of the body. If this folding fails, disaster strikes and the proteins malfunction. The most glaring gaps in knowledge of this folding phenomenon come with membrane proteins. We propose to forge new territory by devising new methods to understand membrane protein folding. We intend to work out what makes the receptor unstable and investigate how to ensure it folds correctly.