Life After the Human Genome Project: TSRI Researchers Spearhead Protein Structure Initiative

By Mika Ono

The human genome has been sequenced. Now what? According to The Scripps Research Institute (TSRI) Molecular Biology Professor Ian Wilson, one of the next steps is to focus on the proteins the genes code for—to find what these proteins look like and what they do.

“Right now there is no way to look at most amino acid sequences [determined by a gene] and tell what the protein looks like,” comments Wilson. "To be able to do this would represent an important advance in our understanding."

The National Institutes of Health (NIH) seems to agree. Under the auspices of The National Institute of General Medical Sciences, the NIH recently launched a nationwide initiative on protein structure determination, with an emphasis on developing high-throughput technology that could one day support efforts to find and catalog the structures of all proteins active in the human body. In 2000, the NIH awarded roughly $30 million for the first year to seven centers—one of which is headed by Wilson.

One of the first tasks of the centers will be to organize all known proteins into structural ("fold") families based on their genetic sequences. The centers will then determine the structure of one or more proteins from each family. The stated goal of the NIH is to determine 10,000 new protein structures in 10 years, forming the backbone of a public resource linking information on sequence, structure, and function.

A New Way of Doing Science

According to Wilson, the NIH Protein Structure Initiative is a dramatic departure from science as usual.

"The ambitious goals of the project have led us into new territory," he says. "To my knowledge, this is the first time the NIH has funded technology centers instead of hypothesis-driven research, like RO1s. But the logic goes that over the long term, the new high-throughput technologies will help drive discoveries."

The large scope of the project also has implications for the way research is organized. "This kind of project encourages multi-institutional collaborations," Wilson comments. "This is a different way of doing science—and a different way of competing—but one I believe we'll be seeing increasingly in the future."

Wilson's group, dubbed the Joint Center for Structural Genomics, draws on talent from several top-notch California institutions, both public and private. The main players are: TSRI, The Genomics Institute of the Novartis Research Foundation (GNF), University of California at San Diego (UCSD), and the Stanford Synchrontron Radiation Laboratory (SSRL, a Division of the Stanford Linear Accelerator Center, SLAC) at Stanford University.

More than 60 researchers are involved in the consortium, which also includes collaborators from around the world and from other local institutions, such as The Salk Institute. Other TSRI scientists affiliated with the project include: Ruben Abagyan, Geoffrey Chang, Jack Johnson, Peter Schultz, and Ray Stevens.

The group will receive $24 million over five years (funds that are in addition to, not instead of, those supporting more traditional NIH projects).

"Spread among multiple institutions over five years, the amount isn't as significant as it first seems," comments Wilson. "But we're still in the pilot stage of the NIH initiative. To me, the important thing is to be involved from the beginning."


Next Page | 2000 protein structures

1 | 2 |


Professor Ian Wilson (left), shown here working with graduate student Dennis Wolan, heads a consortium of researchers developing high-throughput technology to find and catalog protein structures.