ability to engineer better specific substrates – small molecules called ligands – that modulate their activities. “In particular, knowing 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,” says Milon. For example, Diovan, Plavix, Advair and Abilify are all drugs that fall within this category, and together they represented a total market of approximately 30 billion dollars in 2009. The network was funded to recruit and train young researchers in
the structural determination of
membrane proteins. All of the students specialise in one specific area at their host lab, but are also exposed to other fields by collaborating within or outside the network. This includes lab visits and exchanges, workshops organized by the network and participation in the network’s annual meetings. In addition, they receive feedback on their research from experienced scientists within the network, through presentations at
the annual meeting and a tutorship system.
Complementary skills workshops and contacts with the private sector are also encouraged and organised within the network. “So far, the programme has produced about 40 peer
reviewed publications, and there are many others due to be released in the coming years,” says Milon. “The results from the various research projects have lead to new knowledge and technical improvements in the field of membrane protein structure and study. “Not only this, we have also trained a new
generation of researchers in the major biophysical methods used in the structural biology of membrane proteins, and it is these young researchers who will be the scientific leaders of tomorrow.” Looking to the future, Milon is confident that the
network can play an important role in the future of membrane
structural biology. “The next step of
membrane structural biology will be moving toward ‘cellular structural biology’ i.e. our capacity to describe membranes at atomic resolution on intact membranes or living organisms. This has already started within our consortium, and major
results
have been obtained in that direction (such as cellular solid state NMR) but it will still need major methodological and conceptual advances to become routine in modern biological sciences.” Members of the consortium will also be looking to
target many new therapies and vaccines in the future. “We have some partners whom are working directly with proteins with a human mutation, in order to directly characterise the structural differences with the wild-type protein,” explains Milon.
“Other researchers are using a strategy
developed within our consortium in which ligands for specific GPCRs are screened for, allowing them to isolate those that strongly inhibit or activate the GPCRs and thus could very probably have some therapeutic function.”
★
www.projectsmagazine.eu.com 75
Project Information AT A GLANCE
Project Title: SBMPs: Structural Biology of Membrane Proteins
Project Objective: The objective of the Europe funded initial training network SBMPs is the training of the next generation of young scientists in Structural Biology of Membrane Proteins. This includes the newest concepts and techniques in structural biology, as well as numerical simulations and protein production and characterisation.
Project Duration and Timing: 4 years, September 2008 to August 2012
Project Funding: The project has received funding from the European Community’s Seventh Framework Programme ([FP7/2007-2013] under grant agreement n°211800. 23 PhD students (756 salary months) and 13 young post-docs (168 salary months) have been funded and trained as part of this project.
Project Partners: • 13 European groups were involved in SBMP research: A. Milon (coordinator), J.L. Popot, E. Pebay-Peyroula, H. Vogel, A. Engel, H. Oschkinat, M. Baldus, D. Müller, H. Grubmüller, F. Bernhard, S. Filipek, M. Archer, G. Siegal.
• 4 industrial partners: Sanofi, JPK instruments, Zobio inc, Bruker.
• 14 International invited professors, associated to the network as “visiting scientists”: D. Engelman, R. Griffin, K. Palczewski, O. Soubias, M. Piotto, J. Baenziger, M. Cocco, T. Schmidt, S. Yoshikawa, A. Kuklin, V. Shirokov, M. Engelhard, L. Yaguzhinskiy, G. Bueldt
Main Contact:
Prof. Alain MILON Alain Milon is professor of the “Université de Toulouse”, France. He is leading a group specialized in biological NMR in the Institute of Pharmacology and Structural Biology (UMR 5089, CNRS – UPS). His main research interests are on membranes and membrane proteins, protein – DNA interactions and ligand screening by NMR.
Contact: Tel: +33 5 61 17 54 23 Email:
alain.milon@
ipbs.fr Web:
www.ipbs.fr/?-NMR- and-protein-membrane
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