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EMBL Gets 10 million for Structural Proteomic Standard, Aims for European Competitiveness

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The European Molecular Biology Laboratory last week announced that it had received €10 million from the European Commission to create a standard structure determination platform that unites over 20 European partners — including every synchrotron in Europe — under a single system. Scientists at the Hamburg branch of EMBL will direct the project, which officially launched on Jan. 1 and is called BIOXHIT — for Biocrystallography on a Highly Integrated Technology Platform.

This project is intended to address the current lack of standards for how scientists and synchrotrons approach high-throughput X-ray-based structure determination (see PM 2-6-04).

The EMBL team is not the only structural genomics group leader to face this sort of question: John Norvell, director of the US Protein Structure Initiative, sponsored by the National Institute for General Medical Sciences, noted that organizing things from a central level is a challenge, since “all the scientists running these [projects] have been trained to look at [the problem] in a different way.” (see PM 2-13-04)

On a hardware level, each synchrotron tends to use its own robotics and its own protocol for processing the crystal, so that beamlines between instruments are not interchangeable. “At every step, all the way from preparing the crystals, to getting them to the beamline, to having them mounted on this thing, to having the data analyzed, to getting results — each beamline has one of these areas where it’s really advanced,” Russ Hodge, an EMBL public information officer, told ProteoMonitor.

BIOXHIT aims to solve this discrepency. ”What this project will do is pick out the site that does each step the best, and to try to bring all the other sites up to that standard in a real standardized way,” Hodge said. Since each synchrotron is a little different, Hodge noted, the platform will not be exactly the same for each machine, but they “will at least have extremely compatible robotics.” BIOXHIT will not, however, establish a set protocol for wet lab crystal production. “By the time you get a crystal, it doesn’t really matter where it comes from,” Hodge said.

There are several good reasons for standardizing synchrotrons, Hodge said. First, if beamlines are not standardized, then if a beamline that an investigator initially proposes to use becomes unavailable, the experiment cannot be easily transferred to another beamline. With the standardized system, Hodge said, all samples would be processed in a standard sample tube with a barcode that would track all information associated with the sample, and beamlines will be set up similarly, so the sample can easily “just go off to a different beamline and be done there,” Hodge said. Related to this, another advantage will be the ability to timeshare. “If you can’t get beam time on one beamline, then you don’t have to go through a completely new submission — it will be distributed among the other beams,” Hodge said. In addition, standardization will allow for better quality control, Hodge said.

The EC funding, which covers the first four years of a planned approximately 5-year project, will be supplemented by about $700,000 from another European source that Hodge did not divulge. But “to really get everything going, they’re going to have to be able to draw in other funding” as well, Hodge said. The goal is that standard platforms will be in place by the time several new synchrotrons open in 2006 and 2007, so that the new machines can integrate the platforms into their beamlines from the start. Still, “getting everything up to speed will vary quite a bit from beamline to beamline,” Hodge said.

The ultimate goal of this grant, is to “make Europe a substantial player in this area” of high-throughput crystallography, according to EMBL-Hamburg grant coordinator Victor Lamzin. “Similar initiatives are already underway in the US and Japan, our two main competitors in this area,” he said in a statement. The NIGMS, for one, is likely to commit another $75 million to structural proteomics in FY 2005 (see PM 2-13-04).

— KAM

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