Now the new European Drug Initiative for Channels and Transporters project (EDICT) is set to change this, with €15m Euros of research dedicated to determining and exploiting the structure of these proteins. Once the structure of these proteins has been uncovered, suitable drugs may be found to manipulate the activity of proteins to help treat associated diseases.
"[We hope to gain] sufficient detail of the intimate structure of each class of protein in order for the chemists and industrial sponsors to design and develop drugs to manipulate their activities in order to overcome disease," said Peter Henderson of the University of Leeds, who is directing the project.
Membrane proteins constitute roughly one third of all the proteins in an organism, and they play key roles in many important processes. For example, membrane proteins generate an electrical potential which is used to conduct nerve signals, and they are also important in detecting glucose concentrations and regulating insulin production.
Despite their obvious importance, researchers estimate that less than one per cent of all the 3D protein structures held in proteomics databases detailmembrane proteins. This is largely due to the fact that membrane proteins are hydrophobic - they do not dissolve easily in water - making it more difficult to extract and purify the proteins from the cellular material before they can be imaged using x-ray crystallography, nuclear magnetic resonance imaging and electron microscopy.
Recently, researchers have found new techniques to isolate the membrane proteins, and the new project looks set to expand on this research. These techniques involve genetically engineering host cells to express slightly altered versions of the proteins, in large quantities, that contain a chemical "tag" which can be strongly attached to Nickel. Once the membrane has been separated from the cell's contents, and special detergents have used to release its own proteins, the mixture is washed over immobilised polymers containing Nickel. The desired proteins stick to the Nickel, while the others are washed away, and the structure of these isolated proteins can then be determined using the various imaging techniques.
Until now, however, much of this research has been performed by isolated groups, and EDICT will bring together researchers from academic institutions and commercial companies in many European countries including the University of Leeds in the UK, the Max Planck Institutes in Germany and AstraZeneca in Sweden, to provide a greater understanding of these important proteins.
"The aim of the European grants is to bring together these previously independent, and even competing, activities in order to promote the discovery of new drugs in an age when many diseases are gaining the upper hand, and some are becoming increasingly untreatable," said Peter Henderson.