Yale Bulletin and Calendar

September 20-27, 1999

Volume 28, Number 5

Gerstein's work for Human Genome Project
gets $1 million boost from Keck Foundation

Professor Mark Gerstein's passion is looking at things in a way few people have ever looked at them before.

Briefly, Gerstein's research involves bioinformatics, which is using computers to analyze information in the field of molecular biology, particularly concerning macromolecules, proteins and DNA.

His current project uses computer algorithms to analyze the data generated by the worldwide Human Genome Project, in which scientists are attempting to determine the exact sequence of all 100,000 human genes as well as many genes in model organisms, such as yeast and the fly.

"The amount of information generated by the Genome Project is quite monstrous," says Gerstein, who is assistant professor of molecular biology and biophysics. In fact, it has been said a print-out of the entire human genome would fill 1,000, one-thousand-page telephone books.

"We need a way to organize and analyze this data," he notes. "And, in the process, we need to develop some sort of computer infrastructure to be able to accommodate all of this information."

The value of Gerstein's work was underscored recently when he become one of only five researchers in the nation to be awarded the coveted $1 million W.M. Keck Foundation grant. The award was made under the foundation's new Distinguished Young Scholars in Medical Research program.

The board members who selected the winners said they were looking for young faculty who seemed likely to become the nation's outstanding scientists over the next two to three decades. The by-invitation-only applicants were drawn from 30 top-ranked universities and medical institutions.

Now, with $1 million at his disposal, Gerstein is in search of skilled computer personnel who would be willing to work with him for considerably less compensation than they could command in Silicon Valley, but with possibly more long-range reward.

Gerstein's team is helping the Genome Project to quantify the vast amounts of information it is generating in two ways. One is using computers to do comparative genomics, where the genes are grouped by protein "folds," biochemical pathways, and patterns of gene expression. He also is developing methods to cluster proteins into fold "families" and to predict structure and function based on sequence similarity.

Gerstein might, for instance, take a pathogen genome, such as one from the tuberculosis bacterium, and look at what it does not share with the human genetic structure. This way, for instance, a therapeutic drug could be developed that attacks the pathogens while leaving healthy cells intact.

In addition, he is looking at the detail of the protein structures associated with each new gene, trying to see how they are "packed" (dense or loose), and how they move from one state to another. He makes "morph molecule movies" by using crystallographic photos of proteins taken at different times and then fills in the blanks to create animation, much as a cartoon animator might do.

More information about Gerstein's lab can be found on the team's wesbsite: http://bioinfo.mbb.yale.edu

-- By Jacqueline Weaver

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Campus Notes