Toronto Star: New approach to Ebola, SARS leads to research award

Wei Zhang feels he could land a full-time job at a mid-sized university someday.

But the young post-doctoral fellow says his current home at the University of Toronto’s Donnelly Centre for Cellular and Biomolecular Research is likely out of his tenure-track league.

“The U of T is a little bit too hard for me I think,” says Zhang, 34. “They’d more (likely) want people from Harvard or MIT.”

Modesty is a good thing in science, says Sachdev Sidhu, a top molecular biologist at the centre. But in Zhang’s case, Sidhu says, it’s entirely misplaced.

“He’s too humble,” says Sidhu, a principal Donnelly investigator and one of Zhang’s key mentors at the College St. facility.

Indeed, Zhang will be honoured Monday at Ottawa’s National Gallery of Canada with a Mitacs Award for outstanding innovation by a post-doctoral student. His insights on fighting deadly viruses such as Ebola or SARS are what’s made him stand out.

The awards are presented by Mitacs, a non-profit group that promotes innovative links between some 60 universities, thousands of companies and federal and provincial governments across the country.

Zhang’s award, one of seven being presented at the Ottawa ceremony, comes with $500 but a wealth of prestige for recipients, says Sidhu, who helped nominate his apprentice.

Under the tutelage of Sidhu and senior Donnelly scientist Jason Moffat, Zhang has been working with small proteins known as ubiquitins.

In keeping with their name, these short amino acid chains are ubiquitous, present in almost all plant and animal tissues — performing a multitude of functions essential to the protection and well-being of their constituent cells.

For example, some ubiquitins act as garbage collectors. They help tag and dispose of other cellular proteins that have served their natural functions and are no longer needed, Zhang says. Zhang has led major, multi-centre collaborations that have looked to manipulate such ubiquitin functions to fight cancers and other ailments.

These efforts have produced several groundbreaking papers, published in important journals, says Sidhu, who calls Zhang “a natural leader.”

But Zhang’s Mitacs award recognizes his current research and his novel insight — that ubiquitins might be employed to fight emerging and deadly viral diseases.

Strategies to fight such pathogens as Ebola, SARS and Middle East Respiratory Syndrome (MERS) have largely focused on vaccine development. But vaccines only protect the healthy, Zhang says.

“For people who are infected with the viruses … there is no treatment at all,” he says. “There (has been) no progress for a long time.”

In a conceptual breakthrough, Zhang looked to use another function of ubiquitins — their role as antiviral agents — to develop potential cures.

When viruses invade, they send out their own army of proteins to block the host cell’s antiviral defences — specifically neutralizing the ubiquitins the cell employs to guide the counterattack.

“Ubiquitin is required to turn on a (cell’s) viral response,” Sidhu explains. “The viruses produce proteins that remove or inhibit that response.”

In the Donnelly lab, Zhang is developing synthetic ubiquitins to combat this viral onslaught. His engineered ubiquitins are designed to target vulnerable segments of the viral proteins, leaving the cell’s natural immune system intact to rebuff the invading germs.

So far, Zhang’s lab-built ubiquitins have been used to eradicate MERS and Congo Fever — which have 40-per-cent mortality rates — in human cell cultures.

And these results have proven so promising that a start-up company — Ubiquitech — has been launched to commercialize and advance the research.

Sidhu cautions that proteins like ubuiquitins are notoriously difficult to deliver as drugs into living tissues. But he says small molecules — which produce more effective pharmaceuticals — can be designed to mimic their antiviral actions.

Such drugs, if they come, are likely a decade away, Zhang says. But plants, which can be genetically engineered to create their own antiviral ubiquitins, might be part of the new strategy in the near future, Sidhu says.

Zhang was born in China and did his undergraduate studies in Bejing before earning his PhD at the University of Toronto. He has two Canadian-born children.

His interest in viruses grew out of frightening headlines of recent years.

“We noticed on the news that there are many new viruses (that) somehow come from nowhere — Ebola, dengue,” he says. “That’s the big picture (about) why we are interested in creating new antivirus strategies.”

-Joseph Hall, Toronto Star