Columbia University takes leading role in second phase of NIH protein structure

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Columbia University takes leading role in second phase of NIH protein

structure initiative

06 Jul 2005 Medical News Today

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 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, Lawrence

Shapiro, Gouaux, Ming Zhou, 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. , Liang Tong, Hunt, and

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.

Columbia University Medical Center

http://www.cumc.columbia.edu