Harvard Hopes to Capitalize on Genome Draft

Biologists at Harvard reacted with exuberance to the announcement earlier this week that a draft of the human genome has been completed.

"Its a giant symbolic step for us in terms of modern biology," said Joshua LaBaer, Instructor in Medicine and Director of the Harvard Institute for Proteomics.

Harvard has been more of a bystander than a participant in the sequencing phase of the genome project.

Sequencing DNA on the whole genome scale is a massive industrial effort that requires large amounts of expensive equipment--much of which Harvard does not have.

According to Gavin MacBeath, a fellow at the Center for Genomics Research, each sequencing center would have "150 of these half million sequencing machines that we have a couple of."

Twelve centers are dedicated to the project, with several located out of the country.

Many of these centers are linked with universities engaged in technical development of sequencing technology, such as MIT. Technological development of this sort has not been a focus of research on this side of Cambridge.

Now that the sequence data is available, however, Harvard is engaged in several large-scale projects to organize it and to develop technologies that allow for DNA copies of genes to be accessed readily by researchers.

The Harvard Institute for Proteomics (HIP) is working feverishly to develop a system called "The Wall," which will serve as warehouse for copies of all human genes.

LaBaer explained that when complete, the Wall will contain actual "cloned" copies of each human gene in bar-coded test tubes.

Ultimately, the Institute envisions a system from which scientists will be able to obtain copies of the genes they need to work with on demand, eliminating the time-consuming process of individually cloning genes as they are needed for specific research.

Researchers hope to create an Internet-based interface that is connected to a robotic warehousing system for automated access to 200,000 clones.

This vision depends strongly on the development of "recombinational cloning" technologies that allow for genes to be cut and pasted out of the larger sequences of DNA. They will then be stored in the library in a uniform manner.

This system would be flexible enough to allow researchers who want to express a protein in yeast, bacteria, insects, or any experimental system to use the stored genes easily.

Closely linked to this research is the Center for Genomics Research (CGR), which is building a new home in the Cabot Science complex in Cambridge.

One major technology in development at the Center are DNA chips--matrices that contain a large set of genes from a particular organism all mounted on a silicon wafer.

Researchers can use these chips to get a complete picture of genes that are expressed at different times in the life cycle of an animal, revolutionizing a field where genes used to be analyzed one at a time.

The Center plans to serve as a facility that provides these chips to labs in the Harvard community interested in using them in research.

According to MacBeath, the Center currently has parts of 40,000 of the estimated 100,000 to 140,000 human genes stored in their freezer.

The Institute is also actively building a program of fellows who will exploit genomic data for research in fields ranging from bioinformatics to evolutionary analysis.

Currently, MacBeath is the only fellow, but two more are slated to be added by the end of this year, and another two by the end of the following year. The Institute's new home in the Life Sciences Building will have room for ten fellows.

The availability of the human genome sequence will transform the way that Harvard researchers study the genes that cause disease, and help them gain a new understanding of how genomes are constructed in a comparative perspective.

LaBaer explains the challenge for researchers right now is to identify the proteins encoded by each gene and determine its functions.

To do this one has to understand their structure.

"It's the proteins that go bad and cause disease," he said. "All modern pharmaceuticals act at level of protein. None of that info is there in the book of life if you will."

In the next few years researchers will try to solve the three dimensional structures of as many proteins as possible.

Although much remains to be done, researchers agree that the completion of the sequence is a major achievement.

"It's very exciting stuff," said MacBeath. "Philosophically this is the first time in human history where we have the complete set of info that encodes a human being."