Oct 20, 2000


Columbia Scientists Join Next Frontier in Genetic Sequence Research

By Suzanne Trimel

Columbia scientists are joining a five-year, $150 million government-sponsored initiative to study the structure and function of thousands of proteins in the human body, part of the effort to ultimately prevent or treat disease with knowledge from the genetic sequence.

Nine faculty members from the Morningside and Health Sciences campuses are part of the Northeast Structural Genomics Consortium, a research team with participating universities in New York, New Jersey, Connecticut, Canada, Washington State, Israel and Japan. Along with collaborative efforts by other consortiums worldwide, the scientists expect over the next decade to determine the three-dimensional atomic structure of about 10,000 proteins.

The interdisciplinary Columbia team, led by Professor Wayne A. Hendrickson of the department of biochemistry and molecular biophysics, will initially target proteins from several organisms, the fruit fly, yeast and the roundworm, and then move to related human proteins.

John Hunt, professor of biological sciences, said the emerging field of structural genomics is advancing the Human Genome Project to a functional level, and scientists expect the analysis of protein structure will ultimately lead to an understanding of the mechanisms that contribute to health and disease. The project will advance the use of computers and robots to determine protein structure.

For the first year of the research initiative, the National Institute of the General Medical Sciences on September 26 announced $30 million in grants to seven consortiums nationwide, including the consortium that Columbia is part of. The institute expects to commit $150 million over the next five years, making it the world's single largest funder of structural genomics. At $8.5 million, Columbia received the largest individual share of the initial round of funding for the Northeast Consortium, according to Hunt.

Hendrickson, the principal investigator at Columbia, invented a technique in crystallography that makes it possible for scientists to determine the new structures rapidly. This "high throughput" technology is being used in all of the structural genomics efforts.

Encoded by genes, proteins are molecules that carry out the "work" of cells in living organisms. They control the cycle of life and death, rid the body of toxic substances, digest food and oxygenate blood. To fully understand how proteins function and how defective proteins cause disease, scientists must understand the structure of each molecule in excruciating detail since the shape of a protein largely determines its function. Biologists believe there may be 5,000 categories of shapes.

Structural genomics is considered the next and far more challenging step in explaining the molecular underpinnings of living organisms. The goal is to better understand the chemicals that control biological processes in all living organisms. For example, the structure of a disease-related protein can provide insight into how the protein works normally and how a faulty structure can cause disease. This same structure may reveal how to design drugs to treat that disease.

The Northeast Consortium is led by biologist Gaetano Monelione at Rutgers University. Besides Hendrickson and Hunt, other Columbia participants include professors Barry Honig, Eric Gouaux, Arthur Palmer and Burkhard Rost (biochemistry and molecular biophysics), Liang Tong (biological sciences), Andrew Laine (biomedical engineering), Peter Allen (computer science), and Ann E. McDermott (chemistry, biological sciences and chemical engineering and applied chemistry).