Microarray Enhances IITRI's Research Capabilities

Stepping forward on the cutting edge of scientific research, IITRI scientists now have the capability to explore gene expression patterns on a potentially whole genome scale using microarray technology.

Microarrays are collections of hundreds to tens of thousands of small pieces of genetic material representing an organism's genes. It has long been known that, with the exception of identical twins, each individual has a unique genetic make-up.

	"This technology has the capacity to enhance our understanding about drug metabolism, to provide clues for the successful treatment of cancers, and to unravel the intricate molecular mechanisms that define a living cell." Dr. Jonathan Phillips, Research Biologist Microbiology and Immunology

Two new areas of scientific research are concerned with the alterations in gene expression patterns that occur when an organism is exposed to a chemical substance. The first field of microarray research is referred to as "Toxicogenomics" and is concerned with the identification of potential human and environmental toxicants, and their putative mechanisms of action, using genomics resources.

The second field is termed "Pharmacogenomics," which is the discipline of microarray technology that is of greatest interest to the pharmaceutical industry. The goal of Pharmacogenomics is to develop a personal database for each individual that predicts how the individual will respond to a given drug treatment. With this knowledge, drugs could be prescribed with the expectation of a dramatically reduced incidence of negative drug reactions, while increasing the efficacy rate.

Broader View of Gene Expression Patterns Revealed

Using microarrays, scientists explore gene expression patterns on a potentially whole genome scale instead of examining one or a few genes at a time, as was done in the past. Microarrays, though expensive on a per chip basis, are actually a cost-effective means of generating enormous quantities of gene expression data in a relatively short period of time.

	"That's the beauty of this technology; you can really get a global understanding of what's going on," Dr. Evelyn Mobley, Research Biologist Microbiology and Immunology

Of particular interest is how genes interact to influence metabolic pathways and physiological responses to chemical exposure. In the discipline of cancer research, microarray analysis presents a more global assessment of how an organism responds to various agents, including carcinogens or compounds with anti-cancer activity. Moreover, microarrays provide a means for comparing tumor with normal tissue at a molecular level.

Microarray Used in Study of Tumor Growth in Rodents

IITRI has utilized microarray technology to profile gene expression in tumors from rats exposed to chemical carcinogens. For these experiments, RNA, which codes for proteins and represents gene expression, was isolated from tumor and adjacent normal tissue.

Two different colors of probes, one representing tumor, the other representing normal tissue, were produced from the RNA. Next, equal amounts of the two probes were combined and presented to a microarray containing rat-specific genetic elements. The microarray was then scanned with a special instrument to measure the relative signal of each gene represented on the microarray. The preliminary analysis identified several genes that were differentially expressed in tumor compared to normal tissue.

Method Gives Insight into Cancer Prevention

"From these characteristic gene expression patterns, we are gaining valuable insight into the mechanisms of carcinogenesis and cancer prevention," says IITRI's Dr. Jonathan Phillips, who devised the experimental approach and methods employed in the microarray analysis, and interpreted the resulting data. A research biologist in IITRI's Microbiology and Immunology Division, Dr. Phillips has expertise in the application of molecular biological techniques to cancer research, having earned a Ph.D. working in a well-known cancer research laboratory at the University of North Carolina.

By providing an unprecedented view of thousands of genes at a time, microarray technology allows scientists to observe relationships and make correlations about interactions between the genes, says Dr. Evelyn Mobley, the IITRI scientist responsible for isolating the RNA from tissue samples analyzed by microarray. A research biologist in IITRI's Microbiology and Immunology Division, Dr. Mobley received a Ph.D. in Biochemistry and Molecular Biology from the University of Chicago and has expertise in working with nucleic acids. "That's the beauty of this technology; you can really get a global understanding of what's going on," Dr. Mobley says.

Microarray technology is expected to have a profound effect on several avenues of research including toxicology, pharmacology, carcinogenesis, and cancer prevention. "Microarray technology is clearly an immensely powerful technique, particularly when applied in carefully planned ways," Dr. Phillips says. "If used properly, this technology has the capacity to enhance our understanding about drug metabolism, to provide clues for the successful treatment of cancers, and to unravel the intricate molecular mechanisms that define a living cell."