Jim Eberwine: Probing the RNA World
RNA is the bridge between the DNA molecule and the proteins that carry out the functions of life, but probing the intricacies of the RNA molecule deep within the cells it influences is a major challenge. Studying gene expression in cells in culture outside of their natural environment doesn’t always provide a true picture. As James Eberwine, professor of pharmacology at the University of Pennsylvania’s Perelman School of Medicine, notes, “the tissue microenvironment shapes the RNA landscape of individual cells.” That means that important insight about cell function, disease processes, or drug behavior might be missed by observations done outside that highly specialized microenvironment.
But Eberwine and his colleagues — including chemists and biologists in Penn’s School of Arts & Sciences — have devised a revolutionary technique for targeting and observing the RNA of a single cell without disrupting its surroundings. Called TIVA (Transcriptome In Vivo Analysis), the method uses a customized “Swiss Army Knife” molecule to tag the RNA inside cells. The TIVA tags remain inert until they’re activated by a laser with a specific wavelength; this breaks open the molecule, revealing preciously hidden parts that can bind to RNA. The precision of the activating laser means that the tags can be introduced to a large tissue culture, but deployed only within a single cell of interest, allowing the RNA within just that cell to be isolated, studied and measured as desired.
Eberwine and his team have so far used the TIVA technique to examine gene expression in single neurons within intact brain tissue, providing a previously unavailable functional window into the cellular universe.
As one of the directors of the Penn Genome Frontiers Institute, Eberwine is also at the forefront of other interdisciplinary research initiatives that seek to understand the role of RNA’s various forms in health and disease.