February 20, 2003
Computer analysis finds patterns in viral RNA
Medical and health sciences researchers frequently conduct studies in vivo, within the body, or in vitro, in a test tube. Dr. Marcella McClure conducts her research in silico.
“My work is conducted in the computer environment,” explains McClure, associate professor of microbiology and computational biology at Montana State University. “I look at retroid agents in silico. I take empirically derived biological data sources, such as gene sequences, along with bioinformatics tools, like the Blast algorithm, and use human decision-making to generate new knowledge about the evolution, structure, and function of RNA-based life forms.”
Retroid agents are genetic agents that replicate or transpose themselves via a ribonucleic acid (RNA) intermediate and encode the reverse transcriptase. One example is the human immunodeficiency virus (HIV). Retroid agents have coevolved with multicellular life forms and cause diseases such as muscular dystrophy and hemophilia. Not all retroid agents are pathogenic. Experimental work indicates that retroid agents play a role in normal animal development and reproduction, including in humans.
However, when it comes down to the numbers, what is most important is that RNA mutates faster than DNA. McClure and her lab colleagues develop and test software to analyze RNA sequence data.
“RNA can mutate at least one million times faster than DNA life forms,” says McClure. “RNA evolves so fast that you can see molecular mechanisms that would take generations to see in a DNA system.”
Research using viruses provides model systems to apply to DNA mechanisms. For instance, gene splicing was originally discovered as a mechanism for viral messenger RNA before it was observed in host messenger RNA.
“One of my goals is to develop a browsible database of existing and new data relevant to retroid agents,” says McClure.
Already McClure and her colleagues have successfully predicted the function of several proteins based on sequence analysis. Her in silico predictions have been validated by crystallographic analysis in experimental laboratories.
McClure doesn’t think that the future of biology is all in silico.
“No algorithm is as good as the human eye at recognizing patterns at this level — the amino acids that are common among distantly related enzymes, for example, are those that fold into the active site of an enzyme or confer some important structural integrity,” says McClure. “People who do this kind of work are good at seeing patterns. What is a pattern to me, may not be a pattern to you.”
McClure will present “Hunting for the Reverse Transcriptase Gene: The Bioinformatics of Retroid Agents; Disease, Function and Evolution” at the WWAMI Science in Medicine lecture, at noon, Thursday, March 6, in D-209 Turner Auditorium, Health Sciences Center. The lecture is open to everyone.
McClure received a Ph.D. in molecular biology in 1984 at the Washington University School of Medicine in St. Louis. She completed a postdoctoral fellowship at the Center for Molecular Genetics at the University of California San Diego and was an assistant research professor in biology at UC San Diego and in ecology and evolutionary biology at UC Irvine. From 1993 to 1999 McClure was assistant professor of biology sciences at the University of Nevada Las Vegas. She joined the Montana State University faculty in 1999.
Among numerous honors, McClure received a National Institute of Allergy and Infectious Disease Research Career Development Award in 1996.