SAN FRANCISCO, July 17 - Not content with having the world's brightest source of X-ray light to get at a protein's 3D image, Lawrence Berkeley National Laboratory has been adding robots and advanced software to make the effort truly high throughput.
"Now that the genome sequence has reached a number of milestones, the knowledge of the 3D structure [of proteins] is important to determine how molecules work," said Thomas Earnest, head of LBNL's Berkeley Center for Structural Biology, based here. "If you can pick your best crystal and optimize without human intervention, you gain time savings by three or four fold."
In March 2001, the center converted one of its beam lines, an X-ray accelerated along the curve of a synchrotron, into an automated operation. In this process, which the lab predicts will eventually save weeks in protein analysis while freeing researchers from repetitive tasks, a robot mounts and centers onto an X-ray field a protein crystal lifted from a container housing 112 cryogenically cooled crystals.
Last winter the center retrofitted a second beam line and recently added "smart software" that chooses the best crystal to study, tracks the data, and builds a 3D image from the results, said Earnest,
It will take about a year to integrate the software with the hardware before researchers can reduce from days to hours the time it takes to collect data, and from weeks to days the time required to process the data, said Earnest. Currently, two beam lines have robots and two additional lines are under construction and slated for operation by the fall, he added.
Time savings have already been realized, and organizations funding the effort are already betting with dollars that greater efficiency will be realized: Amgen, Roche Biosciences, Howard Hughes Medical Institute, Syrrx, and the Genomics Institute of the Novartis Research Foundation have all made sizeable grants to Berkeley Labs in exchange for time on the beam, said Earnest.
Additionally, a number of companies has kicked in millions of dollars at various stages of the tool's development to guarantee their own sizable chunk of X-ray time: Howard Hughes contributed an initial $8 million for beam-line construction and continues to pay $600,000 annually for operational costs for two beams, according to Earnest.
The funds allow Howard Hughes investigators to use a beam line for 75 percent of its operating time. The other 25 percent goes to researchers submitting a proposal, who get their time for free unless the research is proprietary. In that case, they can expect to fork over approximately $1,500 for an eight-hour spin on the machine.
The Genomics Institute of the Novartis Research Foundation and Syrrx, meanwhile, share 75 percent of the time reserved on another beam line after kicking in an initial $2 million and promising to shell out $450,000 in annual operating costs, said Earnest.
Part of the center's approximately $4 million annual budget also comes from the US Department of Energy and the National Institutes of Health, Earnest added.
Other players are also getting into the automated-synchrotron protein-analysis game: The structural molecular biology group at Stanford and the European Synchrotron Radiation Facility in Grenoble, France, are slated to have automated facilities in operation within a year.