New $52.7 Million Protein Research Program

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• News Release
• Professor Montelione's home page
• CABM Protein NMR Spectroscopy Laboratory
• Press Release on innovative NMR methodology from University at Buffalo

A Rutgers-led $52.7 million research program will help reveal the roles that proteins play in life's most fundamental processes and point the way to designing new medicines. Under the direction of Rutgers Professor Gaetano Montelione, the Northeast Structural Genomics Consortium (NESG) will conduct the five-year undertaking.

The research program is funded by the Protein Structure Initiative (PSI) of the National Institute of General Medical Sciences (NIGMS), one of the National Institutes of Health. This is part of a national effort to find the three-dimensional structures of a wide range of protein molecules, building upon the momentum created by such groundbreaking programs as the Human Genome Project. However, the majority of the proteins coded by the genome have unknown functions and unknown structure.

For the past five years, Montelione and his consortium partners conducted a $36 million NIGMS pilot program to develop new methods and tools to streamline and speed many of the laborious steps involved in generating protein structures.

The researchers applied the new technologies to determining three-dimensional structures of approximately 200 proteins, representative of some of the 100,000 protein families that are estimated to exist in nature. These structures, in turn, have provided templates for predicting models of more than 40,000 protein structures using methods of structural bioinformatics. Other NIGMS pilot program centers brought the total to about 1,500 structures which can be used to model thousands of other proteins in each of the families they represent.

NIGMS has now funded four of the strongest pilot program centers, including NESG, as Centers for Large-Scale Structure Production. The focus is shifting to a production phase during which 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.

Montelione expects that in the next five years his group should solve about 1,000 more structures, including many human protein structures, using methods of X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy, with the full PSI producing a total of about 4,000 - 5,000 over the next five years. "These structures will have tremendous value in understanding basic biology, and in developing the next generation of diagnostics and medicines for treating human diseases," said Montelione.

NESG is a Rutgers-led collaborative research partnership of more than 15 principal investigators and 120 scientists at nine universities and other research facilities. Approximately $20 million will fund research at Rutgers, which will be the central hub of the program. The remaining $30 million will support work at NESG partner institutions.