NIGMS Structural Genomics Awards scale up protein structure studies

September 25, 2000

If genes are the recipes for life, then proteins are the culinary result--the very stuff of life. Proteins control many biological processes in organisms ranging from bacteria to plants and humans. One way to understand proteins--and perhaps find ways to control their action--is to decipher their three-dimensional structures.

The National Institute of General Medical Sciences (NIGMS) has developed a major new initiative to determine the structures of thousands of proteins over the next decade. Work toward this goal will be divided into two phases: a five-year pilot stage and a subsequent five-year full-scale production phase. The initial phase begins with today's announcement of the first awards for pilot research centers in structural genomics, a new field dedicated to a broad understanding of protein structures and functions in relation to gene sequences.

NIGMS is awarding almost $30 million this year to seven projects, each totaling around $4 million for the first year. The Institute anticipates spending a total of around $150 million on these projects over five years, making NIGMS the world's single largest funder of structural genomics.

"This project can be viewed as an inventory of all the protein structure families that exist in nature," said Dr. Marvin Cassman, NIGMS Director. "We expect that this effort will yield major biological findings that will improve our understanding of health and disease."

Structural genomics, which builds on genome sequencing efforts, can teach us fundamental lessons about biology and can advance efforts in structure-based drug design. For example, the structure of a disease-related protein can provide insight into how the protein works normally and how a faulty structure can cause disease. This same structure may reveal how to design drugs to treat that disease.

Although structure determination techniques--chiefly X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy--have advanced dramatically in recent years, they are still time-consuming and labor-intensive. The research centers funded by NIGMS seek to streamline and automate these techniques, as well as every other task in structural genomics, ranging from selecting proteins for structure determination to analyzing the final data.

"These research centers are true pilots," said Dr. John Norvell, director of the NIGMS Protein Structure Initiative. "Each will include every experimental and computational task of structural genomics and will develop strategies for use in the subsequent large-scale research networks. By the fifth year of the award, we expect each pilot center to reach a production level of 100 to 200 protein structures annually, which is significantly greater than the current rate of protein structure determination."

The centers will begin their work by organizing all known proteins into structural ("fold") families based on their genetic sequences. They will then determine the structure of one or more proteins from each family, for a total of about 10,000 protein structures in 10 years. This information will form the foundation of a public resource linking sequence, structural, and functional information. The resource will also allow scientists to use gene sequences to predict the approximate structures of all other proteins.

The awards are listed below alphabetically by the name of the principal investigator.
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CONTACTS
To arrange an interview with Dr. Marvin Cassman, NIGMS Director, or with Dr. John Norvell, director of the Protein Structure Initiative, call Alisa Machalek in the NIGMS Office of Communications and Public Liaison at (301) 496-7301.

More information about the NIGMS Protein Structure Initiative is available at http://www.nih.gov/nigms/funding/psi.html .

NIH/National Institute of General Medical Sciences

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