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Public Structural Genomics Initiative Revs Up Domestic, Int l Efforts

WASHINGTON, Feb 8 – The National Institute of General Medical Sciences, a division of the NIH, is ramping up its commitment to elucidate thousands of protein structures over the next few years with a recently announced promise to fund three centers to develop high-throughput techniques and a plan to facilitate international cooperation.

The NIGMS’ Protein Structure Initiative will award $3 million to $4 million annually to each of the three new protein structure centers as part of a $150 million five-year program. Last September, the NIGMS announced seven winners of such grants. The institute also funds grants to individual scientists working in the field.

By the end of the pilot stage, the centers are each expected to be able to determine 100-200 protein structures annually, a level that will kick off a five-year period of full-scale production. All protein structures and other results gleaned from the NIH program will immediately be made publicly available, with coordinates deposited in the Protein Data Bank as soon as they are determined.

The funded centers each consist of consortia of institutions and collaborating scientists. Initially, the program will be loosely integrated, but each center will be required to maintain a web site listing their targets to avoid duplication of effort.

" Once the pilot projects are complete, we'll have a larger-scale operation in the production phase," said John Norvell, director of the Protein Structure Initiative. " There are lots of possibilities as to how that might work. Centers may evolve and grow, or they may join together in a higher level of organization. We're not even trying to guess that right now, because seeing what works best is the point of this pilot period."

While researchers from all over the world are involved in the NIH program, other nations also have their own efforts. The International Structural Genomics Task Force will be meeting in Warrenton, Va., April 4-6. Attendees will discuss priorities and policy and will hopefully start to establish an infrastructure for international cooperation. " Some countries, like Japan, have a greater degree of organization, while others' programs are just being put together," Norvell said.

An international effort to facilitate the eventual release of structures determined in the private sector is among the goals of the task force. One idea being considered is an electronic journal that would aid in speedy publication of protein data.

Both public and private efforts in structural genomics are accelerating in the wake of the completion of the human genome sequence. Advances in x-ray crystallography, nuclear magnetic resonance spectroscopy, bioinformatics, and robotics provide researchers with a powerful toolkit. The sector is also flush with resources. Almost $200 million in venture capital for protein structure projects has flowed into the coffers of GeneFormatics, Structural Genomix, and Syrrx, all based near San Diego.

The big push in structural genomics in both the public and private sectors may be reminiscent of the competition between NIH and Celera to sequence the human genome, which recently ended in a photo finish. But we shouldn't expect another race, Norvell said.

For one thing, unlike the Human Genome Project, structural genomics has no finish line. " Completeness means something different here," Norvell said. " We're not going to sequence all the proteins." The emphasis of the public program is also different than that of industry efforts, he added.

The NIGMS project aims to determine the structures of about 10,000 proteins, each representing a different protein family as determined from genome data. By gaining a better understanding of the relationships between gene sequences and protein structure, the project organizers hope to be able to predict the structures of the other proteins in each family. Structure, in turn, will shed light on protein function.

" Industry has somewhat different priorities," Norvell said. " They're looking mainly at medically important proteins for which the function is already known, proteins that have a relationship to disease and drug discovery. We're casting a much broader net -- building an inventory of all the protein structures in nature. We're looking to find new structures, new protein folds. Many of the proteins we'll look at have no known function. If the function is known, the structures have probably already been studied."  

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