Unlocking D.N.A. Secrets

By Sandra Howe
Staff Writer

The O.J. Simpson trial may have told Americans more about DNA than they ever wanted to know, but Prof. Larry McLaughlin (Chemistry) feels DNA's potential in identifying and treating health problems may well attract further interest.

McLaughlin studies nucleic acids - DNA and RNA - and their relationship to problems associated with heredity, genetic disorders, viral infections and cancer. His work, which has attracted $715,340 in external grants for the current year, is helping shed new light on the role of DNA and RNA, and challenging some common notions in biochemistry along the way. Although McLaughlin says practical applications are far in the future, his research may someday change the way medical science diagnoses and combats diseases. Over the past year, McLaughlin has published related articles in the Journal of the American Chemical Society, the Journal of Organic Chemistry and Biochemistry .

"A lot of what we do has a long-term view of ultimately using nucleic acids as pharmaceuticals," said McLaughlin. "The goals are to create agents that work against specific molecular problems resulting in disease or infection, and target genes and alter genetic expression to prevent uncontrolled cell growth that characterizes cancer."

Toward this end, he seeks to understand how information is transferred from the "parent" cell to the "daughter" cells in the body through the interactions of nucleic acids and proteins. DNA sequences are made up of four coding elements, he explained, which are copied and passed onto cells, so each cell contains the same copy of DNA.

"All cells aren't the same, though, so we're trying to understand the controlling mechanisms which dictate that certain parts of the DNA are active in some cells while others are dormant," he explained.

Processes involving DNA and RNA are also important in halting the spread of some infectious diseases, McLaughlin said. "A virus is essentially a packet of genetic material that invades cells, takes over, and begins to produce more of the virus at the expense of the host cell," he said. "So if we can control how genes are expressed, we can potentially turn off the genes of the virus, thus halting the infection."

The National Institutes of Health awarded McLaughlin grants totaling $520,340 for three related projects in this area of research. In one project, McLaughlin attaches fluorescent agents to a "probe" DNA sequence, which is used to "hunt" for a target sequence like a piece of viral DNA or RNA that will indicate potential health problems, McLaughlin said. If the target sequence does not occur, the fluorescent agent generates only a weak signal, he said, but if the diagnostic probe locates the target, the fluorophore binds to the probe/virus complex and generates a bright fluorescent signal.

Another project focuses on a catalytic property of RNA, which commonly acts like a messenger, taking information from the DNA and coding it so proteins can be prepared to catalyze the chemical reactions in a cell, explained McLaughlin. But in some cases RNA can also take part in the chemical reactions in the cell. How this process occurs in the absence of any protein catalyst is not yet understood, he said, but the very idea challenges a long-held belief in the biochemistry field.

By understanding RNA catalysis, McLaughlin can work toward the development of nucleic acid-based pharmaceuticals. For example, a piece of catalytic RNA could be designed to target a foreign entity - such as an invading virus - and destroy it without harming the host cell, he said. Before this property of RNA catalysis can be used in a medicinal sense, the basis for this new biological process must first be understood.

For a third project, McLaughlin is creating new DNA building blocks which would result in a triplex, or three-stranded DNA, and effectively neutralize potentially harmful genes, or "oncogenes," which are responsible for the production of a protein that leads ultimately to cancerous growth.

McLaughlin has also received funding from the National Science Foundation and the American Cancer Society for his research.

"All this work relates ultimately to gene expression," McLaughlin said, "and gives us the potential to develop things to benefit the human health condition by treating viral infections and cancers at the molecular level."

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