May 9, 2013

Lecturer seeks to unravel viral replication’s mysteries

Viruses are among the most confounding creatures on the planet.

2012 Vanderbilt Prize Winner Joan Steitz, Ph.D., second from left, with, from left, Susan Wente, Ph.D., Vanderbilt Prize Student Scholar and M.D./Ph.D. student Jacqueline Clauss, who Steitz will mentor this year, and Jennifer Blackford, Ph.D., who oversees Clauss’ neuroscience research. (photo by Steve Green)

Viruses are among the most confounding creatures on the planet.

Since they can only replicate inside another living cell, often by hijacking its reproductive machinery, they have been described as “organisms at the edge of life.”

Understanding how they do it has important implications for human health. Influenza alone has killed more than 1 million Americans since 1984, according to federal health estimates. Just as important, unraveling the mysteries of viral replication can reveal the nature of life itself.

One of the leaders of this effort, Joan Steitz, Ph.D., described her recent work at Vanderbilt University Medical Center last week during a Flexner Discovery Lecture after receiving the 2012 Vanderbilt Prize in Biomedical Science.

“Viruses don’t make things up,” Steitz said. “Viruses acquire pieces from their host cell.” But that doesn’t mean these stolen fragments perform the same function they’d normally do in the cell. “Viruses take these pieces and then very cleverly fashion them to their own ends,” she said.

Steitz, Sterling Professor of Molecular Biophysics and Biochemistry at Yale Medical School and Howard Hughes Medical Institute investigator, is internationally known for her pioneering work with ribonucleic acid (RNA).

She and her colleagues discovered small nuclear noncoding RNAs, and described the precise and critical role they play in splicing and processing pre-messenger RNA as part of protein-containing spliceosomes called small nuclear ribonucleoproteins.

Her lab has helped define the roles that ribonucleoprotein complexes play in autoimmune diseases such as lupus, and in the ability of herpes and other viruses to invade and replicate within host cells. These insights have led to other classes of noncoding RNA including, most recently, microRNA.

Steitz also was honored last week for her exceptional support of women scientists.

The Vanderbilt Prize, established in 2006, recognizes women who are nationally known for their contributions to the biological and biomedical sciences, as well as for their mentorship of other women in science.

Vanderbilt Prize winners receive a $25,000 award and serve as mentors to women who are pursuing graduate studies in the biomedical sciences. This year’s Vanderbilt Prize Student Scholar is Jacqueline Clauss, an M.D./Ph.D. student who works in the laboratory of Jennifer Blackford, Ph.D., assistant professor of Psychiatry and Psychology.

The title of Steitz’s lecture was “Noncoding RNAs: with a viral twist.”

She discussed the ability of Herpesvirus saimiri to infect and transform the T cells of New World primates, causing aggressive leukemias and lymphomas. This virus contains small regulatory “U” RNAs, called HSURs (for H. saimiri U-rich RNAs), which can bind to host microRNAs.

This may be a strategy the virus uses to manipulate host gene expression in a way that enhances growth of transformed cells.

“These are very challenging problems,” Steitz concluded. “Just recently we’ve been making lots more progress in terms of finding molecular mechanisms. I think this is due to technology … that allows us to do this in a more rational way than we could previously.”

For more information about the Vanderbilt Prize, go to https://medschool.vanderbilt.edu/dean/ and click on “Vanderbilt Prize.” For a complete schedule of the Discovery Lecture series and archived video of previous lectures, go to www.mc.vanderbilt.edu/discoveryseries.