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.
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.
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
While 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.
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