Biology
Membrane proteins are of central importance in cellular communications such as signal transduction and ion exchange, and are important targets for a new generation of medicines. Understanding the function of membrane proteins requires their elucidation at an atomic level, i.e. their fluctuations between various conformations and their spatial and temporal organization within the membrane.
The future of membrane structural biology
Despite their importance, detailed information about the function of membrane proteins at a molecular level are scarce because they are very difficult to study. “We realised that more information was needed on the identification and characterisation of different conformations, how they are inserted in their natural environment and how they are organised within the membrane,” says Alain Milon. “In response to this, our consortium organized a
joint training effort involving the major biophysical methods used in the field of structural biology of membrane proteins. Our approach has opened new possibilities for structure-based drug design, in particular towards G-protein coupled receptors, which are among the most important targets of modern medicines. The training provided in this programme will not only create and train high-level academic researchers, but will also make a huge contribution in forming the main actors of the future development of biotechnology and personalised medicine.” The Structural Biology of Membrane Proteins
(SBMP) network combines 12 academic research groups involving specialists in functional/structural analysis and dynamics of membrane proteins, and 4 industrial companies interested in collaborating with these groups and involved in drug discovery or scientific equipment for SBMPs. The network represents about seventy researchers and provides
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state of the art laboratories in all the relevant research disciplines. It is unique in that it covers all of the various methods required in the structural biology of membrane proteins, and ensures that the complementary expertise is of a high technical level and available to all students. Funding for the training of the students is provided
by the FP7 initial training network programme, with the overall budget for the fellow’s salaries, research and training expenses totalling approximately 5.7M Euros. With the cost of research surrounding the fellows and the investment in large equipment, which in this field is particularly important, the actual budget is a lot higher. “Membrane proteins are rather difficult to study due
to their biochemical and biophysical nature, and so we set up a network of specialists in all of the major techniques used to study them,” says Milon. “These include efficient in vivo and in vitro expression systems, X-ray crystallography, liquid and solid state NMR, electron microscopy, atomic force microscopy, single molecule force studies, advanced biochemical/ biophysical and functional characterisation strategies as well as numerical simulations.” One of the most exciting areas of research within
the field of membrane proteins involves engineering their function in order to prevent disease. A better understanding of the structure, dynamics and function of membrane proteins has lead to the
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“The 3D structure of membrane proteins at atomic resolution using X-ray diffraction, NMR or electron diffraction, as well as advanced molecular simulation procedures, has allowed us to perform structure based drug design of specific ligands”
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