Virginia Tech Carilion Research Institute scientists Deborah Kelly and Sarah McDonald are ambitious and determined, and it’s paying off. The two assistant professors recently received a National Institutes of Health grant for their collaborative work developing new imaging technologies that will allow them to see live rotavirus activity.
McDonald and Kelly, whose offices share a wall and whose laboratories are adjacent, began collaborating more than two years ago.
“I was interested in examining RNA-related processes using high-resolution imaging technology,” Kelly said. “Dr. McDonald’s work with rotavirus provided the right opportunity to collaboratively develop innovative tools together, using the virus as a model system.”
Kelly focuses on developing new imaging platforms – specifically those that help capture the dynamic structure of functionally important proteins in human cells. Traditionally, scientists use cryo-electron microscopy to image protein complexes. With the capability to capture more details than ordinary light microscopy, electron microscopes can be used to peer at the invisible world around us, revealing unique information about macromolecules that can affect human health. The samples are frozen in place, keeping the structures close to how they would appear naturally. Researchers take snapshots of the structures and use computational algorithms to construct 3-D models of the imaged structures.
Rotaviruses have three layers, like a foil-wrapped chocolate egg. The innermost layer, the sweet cream, contains double-stranded RNA, the genetic material needed to create more viruses, and polymerases. Polymerases are responsible for manufacturing the messenger RNA molecules that infect a host. When the virus is active, it sheds the outer layer – the foil. Scientists believe that shedding activates the polymerases. The chocolate layer is already permeated with holes, letting the RNA snake out. The virus in this form is called an active double-layered particle.
Inactive double-layered rotavirus particles were previously imaged at a moderate resolution in the 1990s, producing 3-D models that give information about how the active form of rotavirus operates on a molecular level. With Kelly’s improved technology, McDonald and Kelly think they can determine even more details about how the virus functions and infects host cells.