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In Sync at the Synchrotron: Public, Private Efforts Share Limited Resources

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Determining high-quality structures of proteins en masse is a costly business, requiring not only automated protein production facilities but access to synchrotron radiation. No wonder, then, that public and private structural genomics efforts — on both sides of the Atlantic — are coming together to make the best use of available resources.

Last week, four European research institutes created a new structural biology center, Partnership for Structural Biology, in France. PSB has invited a number of companies to become associate members, granting them guaranteed access to a new beamline being developed, in return for hard cash.

Meanwhile, earlier this month, the National Institute of General Medical Sciences agreed to transfer leadership for a multi-million dollar award from Rockefeller University to Structural GenomiX. The San Diego-based company will receive part of the grant money — awarded to the New York Structural Genomics Research Consortium — in return for its protein production services and access to its beamline.

The founders of PSB, based in Grenoble, are the European Synchrotron Radiation Facility (ESRF); the Institut Laue-Langevin (ILL), which operates a neutron source; the Grenoble outstation of the European Molecular Biology Laboratory (EMBL); and the Institut de Biologie Structurale (IBS), which has NMR, electron microscopy, and mass spectrometry facilities. According to Edward Mitchell, PSB’s project manager, the partnership is planning new laboratories for high-throughput protein preparation that will be housed in a new building, the cost of which is estimated at €3.6 million. PSB is also planning a new beamline for protein structure determination, with two independent end stations, that is slated to come online next year at a cost of about €3.8 million. However, “at the moment, we don’t have enough money,” to accommodate all these projects, said Mitchell. The four partners have each committed funds, which include contributions from a new European initiative called Structural Proteomics in Europe (see above). This cash will allow the beamline and other projects to go ahead, Mitchell said. PSB also plans to apply for funding from the regional French government and from the EU’s 6th European Framework program.

But to fill its coffers sooner, PSB has invited pharmaceutical and biotechnology companies to join as associate members. “It’s a bit like a golf club where you pay an upfront membership fee, and then there is an annual fee,” said Mitchell. Membership guarantees companies access to shifts at the ESRF beamlines for three years. The money will be used to fund beamline facilities and operation, as well as capital costs, Mitchell said. By the end of the year, he said, PSB hopes to sign up four pharmaceutical companies. The first, Cambridge, UK-based Astex Technology, became a member earlier this month.

According to Astex, being a member works out to be a good deal. “We did this to secure access to ESRF, given that there are more and more structural biology groups who want more and more of these types of beamtime options” said Harren Jhoti, Astex’s CSO. Overall, he said, the arrangement will also save the company money.

Another step of the public-private structure dance, the transfer of leadership for the New York Structural Genomics Research Consortium from Rockefeller University to SGX, came after the consortium’s principal investigator, Stephen Burley, transferred from Rockefeller to SGX earlier this year.

According to Burley, SGX’s involvement will allow the company to use excess capacity in its molecular biology and protein production platform, and to develop the platform further. “By playing this role in the Protein Structure Initiative, we can use some of that excess capacity and get paid for it,” he said. In fiscal year 2003, which started in September, the company will receive about 30 percent of the grant money for the consortium, or about $2 million.

In return, SGX is responsible for all gene cloning, as well as expression, purification, and biophysical characterization of target proteins from the New York consortium. Proteins are then shipped to the academic labs for crystallization and structure determination. This division of labor, Burley noted, will also allow SGX to test the model of centralized industrial protein production for the later stages of the NIGMS Protein Structure Initiative.

SGX also gives the consortium access to its beamline at the Ad- vanced Photon Source at Argonne National Laboratory. “My guess is that because of the efficiency of data collection at the SGX beamline, most of the data collection will be done in Chicago,” Burley said.

The consortium will continue to choose its protein targets independently of SGX. “Although I have a role in target selection I don’t have a veto,” Burley said.

While other Protein Structure Initiative centers involve scientists from industry, SGX is the only company that heads a consortium, said the initiative’s director at NIGMS, John Norvell. Before agreeing to the transfer, he said, “we made sure that all of our requirements about data release and sharing information and materials would be adhered to.”

— JK