NIGMS Structural Genome Initiative

Seven new grants, four of them awarded to scientists at DOE sites, are key components in the Structural Genome Initiative started by the NIH National Institute of General Medical Sciences (NIGMS). Over the next decade, the new study will determine the form and function of thousands of proteins.

"These awards demonstrate the continued importance of the physical sciences to life-science research and the strong role the national laboratories play in providing expertise and world-class facilities in our quest to understand the structure and function of genes," noted Dr. Mildred Dresselhaus, Director of the DOE Office of Science.

Proteins come in many sizes and shapes, and their functions often depend on tiny structural details. Obtaining the 3-D structure may help scientists understand how each protein functions normally and how faulty structures can cause or contribute to disease. We expect this effort to yield major biological findings that will improve our understanding of health and disease, said NIGMS Director Marvin Cassman in announcing the grants. These data also can help in designing drugs that bind to the proteins and affect their activity.

The grants total around $4 million each for the first year. NIGMS plans to spend about $150 million on the seven grants over the next 5 years. The four DOE-involved projects are listed first below. Investigators at DOE national laboratories also are involved in some of the other projects.

Grant Recipients, Team Leaders, Specific Goals

* Structural Genomic Center (Sung- Hou Kim, Lawrence Berkeley National Laboratory): Speed up structure determination by X-ray crystallography; study proteins essential for independent life by focusing on two extremely small, closely related bacteria (Mycoplasma genitalium and M. pneumoniae).
* Tuberculosis Structural Genomics Consortium of 13 institutions in 6countries (Tom Terwilliger, Los Alamos National Laboratory): Determine and analyze structures of about 400 proteins from Mycobacterium tuberculosis to facilitate new and improved drugs and vaccines for tuberculosis.
* Midwest Center for Structural Genomics consortium of seven institutions (Andrzej Joachimiak, Argonne National Laboratory): Reduce the average cost of determining a protein structure from $100,000 to $20,000; select protein targets from all three kingdoms of life, with emphasis on previously unknown folds and on proteins from disease-causing organisms. New York Structural Genomics Research Consortium of five institutions (Stephen K. Burley, Rockefeller University): Develop techniques to streamline structural genomics and solve several hundred human and model-organism protein structures.
* Joint Center for Structural Genomics (Ian Wilson, Scripps Research Institute): Develop high-throughput methods for protein production, crystallization, and structure determination by initially focusing on novel structures from Caenorhabditis elegans and human proteins thought to be involved in cell signaling; determine structures of similar proteins from other organisms to include the greatest number of different protein folds.
* Northeast Structural Genomics Consortium (Gaetano Montelione, Rutgers University): Target proteins from various model organisms including the fruit fly, yeast, and roundworm and related human proteins; use both X-ray crystallography and nuclear magnetic resonance spectroscopy to determine protein structures.
* Southeast Collaboratory for Structural Genomics (Bi-Cheng Wang, University of Georgia): Analyze part of human genome and all of two representative organisms, C. elegans and Pyrococcus furiosus; emphasize technology development, especially for automated crystallography and nuclear magnetic resonance imaging techniques.