July 1, 2005

Protein Rush at the NSLS

Recently, the Protein Structure Initiative (PSI) launched the second phase of its national effort to find the three-dimensional shapes of a wide range of proteins. This is good news for the NSLS, since many of those structures will be determined here. But more importantly, the structural information will help reveal the roles that proteins play in health and disease and will help point the way to designing new medicines.

The highlight of the PSI second phase is the announcement of 10 new research centers, which marks the second half of the decade-long initiative. The centers are slated to receive about $300 million in grants over the next five years.

When the PSI established its pilot centers in 2000, its goal was twofold: to develop innovative approaches and tools, such as robotic instruments, that streamline and speed many steps of generating protein structures, and to incorporate those new methods into pipelines that turn DNA sequence information into protein structures.

Three protein structures determined at the NSLS as part of the Protein Structure Initiative.
Images courtesy www.nysgrc.org.

Now, the focus shifts to production. The new centers will use methods developed during the pilot period to rapidly determine thousands of protein structures found in organisms ranging from bacteria to humans. These efforts will facilitate structure determination on a much larger number of proteins through computer modeling.

The PSI production phase includes two types of centers. Four large-scale centers, established during the pilot phase, hope to generate between 3,000 and 4,000 structures. Six smaller, specialized centers will develop novel methods for quickly determining the structures of proteins that traditionally have been difficult to study. These include small protein complexes, proteins that attach to a cell's outer "skin," or membrane, and many proteins from higher organisms, including humans.

As before, the PSI centers will submit their structures and related findings to the Protein Data Bank, an NSF- and NIH-supported public repository of three-dimensional biological structure data.

The Protein Structure Initiative is funded largely by the National Institute of General Medical Sciences (NIGMS) and also receives funding from the National Center for Research Resources. Both centers are part of the National Institutes of Health.

More on How BNL and NSLS are Involved

In 2000, an organization called the New York Structural GenomiX Research Consortium was formed as part of the PSI pilot program. During the pilot period, members of this consortium developed many innovative methods and determined approximately 200 new protein structures. The majority of these structures were deciphered at the NSLS, with about 50 of them being determined by Brookhaven scientists. In fact, two of the consortium's principal investigators are Brookhaven Lab biologists Subramanyam Swaminathan and William Studier.

In the second PSI phase, the Brookhaven group will continue to solve structures at the NSLS and work to improve their methods. Over the five years, the consortium will receive approximately $48 million, with about $9.5 million of that supporting research at Brookhaven Lab.

The consortium's other member institutions are Albert Einstein College of Medicine, Mount Sinai School of Medicine, The Rockefeller University, and Weill Medical College of Cornell University.

ARTICLE BY: Laura Mgrdichian