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On June 8, a European research consortiumlaid the first stone of a new high-throughputstructural proteomics platform in Grenoble,France. The platform is designed to help findways of producing high-quality crystals ofpoorly expressed proteins—a bottleneck instructural biology—so that their structurescan be resolved and used for drug design.With the new platform and the concentrationof multidisciplinary expertise in structureresolution in the region, European biotechresearchers and companies will be fullyequipped to address proteins whose struc-tures are difficult to resolve, once long-termfunding has been secured.

Biotech companies have an increasinginterest in the determination of protein struc-tures because this approach is becoming a keyaspect of targeted drug design. Until now,Europe had only scattered structural biologyinitiatives. By 2005, biopharmaceutical com-panies will have more support in determiningprotein structures, thanks to a new platformset up by a research consortium called thePartnership for Structural Biology (PSB). Theplatform is backed by research laboratoriessuch as the European Molecular BiologyLaboratory (EMBL) outstation in Grenoble,and is “very timely,” according to AlbertoPodjarny, a structural biologist working ondrug design at the Institute of Genetics andMolecular and Cellular Biology (IGBMC) inStrasbourg, France.

The new platform is designed to help tosolve the biggest bottleneck in structural biol-ogy: protein expression. Many biologicallyimportant protein targets, such as membraneproteins, are poorly expressed or have poor

solubility and yield, which makes them diffi-cult to crystallize—and their structures there-fore difficult to determine. The Europeanapproach lays more emphasis on solving diffi-cult protein structure than do structuralgenomics programs at the US ArgonneNational Laboratory and at RIKEN’s syn-chotron in Hyogo, Japan, which were set up tofind as many protein structures as possible asquickly as possible.

To solve difficult protein structures, thenew platform focuses on high-throughputprotein expression and crystallization tech-nologies. For example, one PSB team, led byDarren Hart at EMBL, has developed aprocess by which a problematic protein isfragmented into thousands of possible forms,which are then cloned and tested for expres-sion. Single and multiple domains from thetarget can then be isolated in a soluble form

and taken forward intocrystallization trials.“Thebiological technologiesbeing developed at thePSB are also attractingthe interest of compa-nies,” adds Hart.

Once PSB has helpedthem obtain better pro-tein expression and bet-ter crystals, companieswill then need to deter-mine the structure oftheir proteins (see Box1). As part of its multi-disciplinary approach,the PSB offers access toexisting facilities for

structure determination provided by itsGrenoble-based members, including X-raycrystallography at the European SynchrotronRadiation Facility (ESRF), neutron scatteringat the Institut Laue-Langevin (ILL), and high-power NMR, mass spectrometry and electronmicroscopy facilities at the French Institute ofStructural Biology (IBS). In addition, the PSBbuilding will host a deuteration laboratory—unique in the world—that enables isotopiclabeling of protein complexes used as a com-plementary technology to greatly enhancestructural information on proteins.

In addition, a number of local biotechstartups are already contributing specifictechnology to the initiative, including the Grenoble-based Protein’eXpert, high-throughput producers of recombinant proteins, whose cofounders were both res-earchers at the IBS. The PSB partners hope toencourage the creation of spinoff companiesin the region as a result of the initiative andalso to attract industry-sponsored stu-dentships as a way of enhancing collaborationwith industry.

The potential of the PSB might not come tofruition, however, if the partnership fails tosecure adequate funding to fully develop itsservices. The European Union is fundingsome of the research posts through Europeanresearch networks such as SPINE (StructuralProteomics in Europe), and additional sup-port has come from a regional genomics ini-tiative. But the PSB is currently looking to theEuropean Commission to provide 10% of itsforecasted €17 ($20) million infrastructurebudget over the next five years; meanwhileacademic partners are being asked to providethe rest.

Sally Goodman, Paris

Europe makes way into structural biology

NATURE BIOTECHNOLOGY VOLUME 22 NUMBER 7 JULY 2004 793

Box 1 New synchrotron beamline to determine structures

Among the complementary technologies available at PSB for structure determination, a new,highly automated macromolecular crystallography beamline provided by ESRF has attracteda lot of attention, in part because it is the most powerful synchrotron radiation source inEurope. “We are essentially interested in access to the new beamline,” confirms VincentMikol, head of structural biology at Aventis Pharma in Paris. Aventis Pharma and four othercompanies, including Astex Technology, have privileged access to the beamline as associatedmembers of the PSB.

The high level of automation of the new beamline is designed to reduce the amount of timeresearchers need to spend there, and will completely change the strategy for working withsuch equipment, according to Sine Larsen, ESRF life sciences director and vice-chair of thePSB. Nonexpert users can have easier access to the technology, thus opening up thespectrum of possible users from industry and academia as researchers increasingly recognizethe importance of accurate target protein structure determination in drug design. “Thesynergy between these techniques and the rapid flow of information between teams workingon a single site is very important,” says Podjarny. SG

Structures of difficult proteins, such as cell membrane proteins that areoften used as drug targets, can now be resolved in Grenoble.

ESRF/Studio de la Révirée

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