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Past Winner
2005 E.W.R. Steacie Memorial Fellowship

Andrew White

Biochemistry

York University


Andrew White
Andrew White

Defeating some of the world's most destructive and deadly viruses will require us giving their genetic complexity a lot more respect, says Dr. Andrew White, one of six winners of the 2005 NSERC E.W.R. Steacie Memorial Fellowship.

Big Idea: "Instead of thinking of viral RNA as a passive messenger of genetic information, we need to view RNA as a very active regulator of essential processes in the viral reproductive cycle," says Dr. White, a viral biochemist at York University and the Canada Research Chair in Plant Biotechnology and Structural Biology.

The Question: How do many of the world's most medically and agriculturally important viruses regulate their behaviour? At first glance the answer might seem simple: It's the viral proteins doing the job. After all, most of these so-called positive-strand RNA viruses contain only a single molecule of RNA, or ribonucleic acid. They include the largest group of crop-damaging viruses as well as such human pathogens as the SARS coronavirus, the West Nile virus and the Hepatitis C virus.

In the cellular context, RNA is viewed primarily as DNA's handmaiden, a messenger carrying instructions from the nucleus to the cellular machinery that produces proteins. Likewise, biologists have traditionally viewed RNA viruses in the same way, believing that viral proteins are really calling the plays. Not so, says Dr. White. RNA is actually far more controlling than previously imagined. In fact, the viral genome is actually a collection of intelligent RNA sub-units that are responsible for regulating other molecules. "What's now clear," says Dr. White, "is that through various interactions or by changing shape, RNA elements actively regulate key steps in viral infections. They are the real conductors of the viral orchestra."

Research at the Edge: Dr. White's lab is pioneering the identification and characterization of functional RNA sub-units in the Tomato bushy stunt virus, a positive-strand RNA virus. He's shown that specific sections of RNA, called viral riboregulators, play central roles in controlling key viral processes. These include the translation of viral proteins and the replication of the viral genome. The research has revealed that there are at least three major types of viral riboregulators: RNA bridges, gates and switches. Dr. White's lab has identified new types of RNA bridges that unite distant regions of the viral genome and work as a tag team to boost the production of viral proteins. His group has also produced the most advanced functional model for how RNA gates operate to cause the synthesis of specific viral messages. And, intriguingly, his team has discovered RNA switches which through their structural changes turn viral replication on or off.

Importantly, Dr. White believes that the uniqueness of these riboregulators makes them ideal targets for inhibiting viral infections. "The distinct structural features of these viral RNA elements should allow for the development of inhibitors that will specifically target the virus and not the infected cells," he says.

The Next Step: As part of his NSERC Steacie Fellowship research, Dr. White will continue a "search and discovery" mission to identify additional riboregulators in the Tomato bushy stunt virus and uncover new RNA elements in other viruses. Impressively, this research extends from the atomic level all the way to the greenhouse. In collaboration with York University colleagues, he'll be using nuclear magnetic resonance spectroscopy to identify the atomic structures of various riboregulators. To see the impact of riboregulator function on the viral infection process, he'll infect plants with genetically modified versions of riboregulators and monitor the spread of the infection and the development of symptoms.

The work will support the global effort to turn the table on viruses. One of Dr. White's ultimate objectives is to gain control over riboregulators and put them to work in biotechnology. "Instead of having viruses hijack our cellular machinery to their ends, the goal is to use bioengineering to manipulate and control riboregulators so that certain viral processes can be refocused to beneficial applications," he says.