Researchers at Columbia University are taking a major role in the second phase of the National Institutes of Health's Protein Structure Initiative, leading or participating in three of the 10 new research centers announced Friday by the National Institute of General Medical Sciences (NIGMS).
The Protein Structure Initiative (PSI) is a national effort to determine the three-dimensional shapes of a wide range of proteins. This structural information will help reveal the roles that proteins play in health and disease and will help point the way to designing new medicines.
Selection of the centers, slated to receive about $300 million over the next five years, marks the second half of the decade-long initiative. Columbia University will receive about $25 million over five years to fund its research contributions.
"The overall idea of PSI is a bit like the Human Genome Project in that the information gained from these large-scale efforts will underpin a more efficient approach to medical research in the future," said Wayne Hendrickson, Ph.D., University Professor of Biochemistry and Molecular Biophysics at Columbia University Medical Center (CUMC) and leader of one of the new centers. "Drug discovery has been lagging in recent years, and many of us believe that the development of drugs based on a protein's structure is a much more efficient way to find the drugs we'd like to have."
The Protein Structure Initiative essentially starts from where the Human Genome Project left off. "Genes are important only in that they produce proteins, which are the tiny three-dimensional machines of life," says Lawrence Shapiro, Ph.D., associate professor in the Departments of Opthalmology and Biochemistry & Molecular Biophysics at CUMC, and a principal investigator of one of the new centers. "This project will enable us to see thousands of proteins in the form in which they actually do their work."
When the PSI established its pilot centers beginning 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.
Now, according to the NIH, the focus shifts 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 accurate structure prediction of a much larger number of proteins through computer modeling.
"We hope that the PSI will allow us to develop a new view of the relationships between protein sequence, protein structure, and protein function that will ultimately make the three-dimensional structures and functions of most proteins predictable from the protein sequence," said Barry Honig, Ph.D., professor of biochemistry and molecular biophysics at CUMC and the bioinformatics leader of the Northeast Structural Genomics Research Consortium.
"We are proud to be contributing to this important effort that is harnessing the brightest minds across a spectrum of scientific disciplines," said David Hirsh, Ph.D., executive vice president for research at Columbia University. "Through this collaborative research we will gain greater insight into how proteins function and their evolutionary interrelationships, ultimately leading to the identification of new targets for drug design."
Columbia researchers will play major roles in the following centers:
- The New York Consortium on Membrane Protein Structure, led by Wayne Hendrickson, University Professor of Biochemistry and Molecular Biophysics at Columbia University Medical Center. Other Columbia researchers include: Drs. Burkhard Rost, Barry Honig, Ann Mcdermott, Lawrence Shapiro, Eric Gouaux, Ming Zhou, John Hunt, and Filippo Mancia.
- The Rutgers-led Northeast Structural Genomics Consortium, led by Professor Gaetano Montelione of Rutgers University. Montelione and his consortium partners previously conducted a $36 million NIGMS pilot program that developed new tools that will now be utilized in this second phase of the project, which focuses on cancer-related proteins. Columbia contributors include bioinformaticians Burkhard Rost, Ph.D., and Dr. Honig, the consortium's director of bioinformatics; Dr. Hendrickson, the consortium's director of crystallography, and Drs. Peter Allen, Liang Tong, John Hunt, and Andrew Laine from Columbia University.
- The New York Structural Genomics Research Consortium (led by Structural GenomiX, Inc., a company co-founded by Drs. Honig and Hendrickson). Dr. Shapiro, will help in high-throughput structure determination, focusing particularly on structures of phosphatases, a type of protein frequently important in disease.