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The Genomic Fast Track

These are heady days for scientists who work with DNA.

Technological advances are providing powerful new tools with which genomics researchers can study DNA and the genes that DNA molecules form. The tools are robots, computers and other equipment capable of dissecting DNA, determining its constituent parts and detecting when genes are active or expressed.

Opperman and Thompson And soon that equipment will have a home in the College of Agriculture and Life Sciences. Completion of a Genome Research Laboratory is under way in the new Partners II building on the Centennial Campus. The 4,000-square-foot, $3 million lab, scheduled to open in the fall, will house equipment that is doing no less than revolutionizing molecular biology, according to Dr. Charles Opperman and Dr. William Thompson.

Opperman and Thompson, who will serve as co-directors of the lab, have overseen its creation. Dr. Bryon Sosinski, a postdoctoral researcher in Opperman’s lab, and Dolores Sowinski, Thompson’s lab supervisor, have also been active in developing the new lab.

Expanding the scale of what's possible

The term genome refers to the sum total of an organism’s genetic code. The Genome Research Laboratory will enable scientists to determine that molecular code — the sequence in which the four nucleotide bases that make up DNA appear along a piece of DNA. The four bases appear millions of times in different sequences along strands of DNA. The code, or the sequence in which bases appear, serves as a cellular instruction for making proteins and defining biochemical functions.

The technology in the new lab will also tell researchers when genes are being expressed, or actively producing the proteins they are supposed to make.

Scientists have known for some time how to accomplish both these tasks — sequencing DNA and determining gene expression. However, with the Genome Research Laboratory comes a dramatic difference: A new technology vastly expands the scale of these abilities. It is now feasible for scientists to sequence the entire genome.

“There has been a revolution in biotechnology,” is the way Thompson, University Research Professor in the department of botany, puts it. “We’ve known how to sequence DNA for a long time,” he adds. “But until recently sequencing an entire genome wasn’t economically feasible.”

Operating at maximum capacity, the Genome Research Lab will be able to determine the sequence of more than 11 million bases a week. That’s in a five-day week. The number jumps to more than 15 million in seven days.

Yet even at a multimillion-base pace, it will take time to sequence a genome, especially for more complicated organisms. The genome of a type of single-celled yeast, for example, contains roughly 13 million bases, a bit more than a week of work for the lab, not counting preliminary organizational tasks.

Steve Lommel has been instrumental in the GRL's development.Similarly, scientists have for some time been able to determine when a gene is being expressed. Using a technique called molecular hybridization, it is possible to detect messenger RNA (mRNA), which is present when a gene is being expressed. But the process was fairly elaborate and time-consuming, involving a good deal of manual labor. In fact, says Thompson, not long ago a doctoral thesis might consist entirely of cloning and analyzing the expression of one gene.

Enter the Genome Research Lab, which will use what is known as microarray technology to do the same thing. But where a researcher would place genes on a membrane filter by hand, microarray technology employs robots and computers to place from 5,000 to 10,000 genes on a microscope slide. Then, using molecular probes to identify genes and evaluating the results with the aid of a high-resolution scanner and sophisticated computer software, a scientist may determine which genes are being expressed.

"A resource, just like the library"

The new technology provides the information, or data; it’s still up to the scientist who asked for the information to determine what it means. But because the technology provides so much more data than was previously the case, it is changing the face of molecular biology.

As Thompson puts it, “We’re simply going to be left behind if we can’t offer access to this equipment. This keeps us in the game of molecular biology.”

Opperman, an associate professor in the department of plant pathology, adds that molecular and genetic research programs must have access to the technology if they are to survive, yet the cost of the equipment prohibits its purchase by most individual scientists.

The College’s facility will be unusual, Opperman says, in that it will not be dedicated to a particular theme or focus. The lab will be available to all faculty members, with an advisory board evaluating research proposals.

“It’s a resource, just like the library,” says Opperman. “It’s designed to enhance the research being done by our entire faculty.”

Opperman and Thompson envision a core of perhaps 50 faculty members using the facility on a regular basis, with others using it irregularly. In an effort to keep the cost of lab use within the funding available in a typical research grant, faculty members will be charged only for the cost of supplies. They must also provide personnel to do their experiments.

Changing the way we think about biology

Partners II buildingWhile the new technology provides only information, not answers, Opperman and Thompson say it is nevertheless changing the way scientists think about molecular biology. Microarray technology, particularly, has given researchers a different view of how genes work.

Molecular biologists used to think of genes as acting linearly: Gene A was expressed, which caused a particular reaction by gene B, and so on. The ability of microarray technology to display the actions of thousands of genes at the same time has changed that view.

“It’s clear now that genes act in concert with other genes in a complicated network of interaction,” says Thompson. Gene A may, in fact, affect gene B, but at the same time gene O is affecting gene A, while in certain circumstances gene L is expressed as well, with a different effect on B, which affects A, and so on.

“The technology has changed so radically, it’s hard to speculate what we can and can’t do,” says Opperman.

Indeed, in some ways the molecule that is the stuff of life is as mysterious as when Francis Crick and James Watson discerned its structure in 1953 — the more scientists learn about the way genes function, the more challenging that function appears.

Scientists know more than they ever have about DNA, and with facilities like the Genome Research Lab, they will learn more still.

Lab is tool to attract faculty

The Genome Research Laboratory will be an indispensable research tool. It undoubtedly will prove as well to be a powerful incentive to attract outstanding new faculty members to the College.

Indeed, if the Genome Research Lab had not been on the drawing board, it is unlikely Dr. Ralph Dean would have agreed to become a member of the faculty of the department of plant pathology, said Dr. O.W. Barnett, department head.

Co-director of the Clemson University Genomics Institute, Dean is an expert on the genetics of fungi, particularly Magnaporthe grisea, the fungus that causes rice blast, a major problem for rice growers around the world.

Dean, who is expected to join the faculty this fall, will bring to the College a well-established and well-regarded fungal genomics program. He will be among faculty members making use of the Genome Research Laboratory and eventually will establish a center focusing on fungal genomics.

Dean’s expertise and emphasis on fungal genomics will enhance the College’s existing fungi-related programs, Barnett said.