The science of proteins and why Dev Sidhu's work matters to you

It's called The Protein Society – and its members include chemists, biologists, physicists, mathematicians, students and educators at universities, foundations, institutes and corporations in more than 50 countries working to understand the structure, function and design of proteins.  

This week, the society awarded Professor Dev Sidhu, of the University of Toronto’s Donnelly Centre, its prestigious Christian B. Anfinsen Award, recognizing significant technological advances in protein science. What does the recognition mean to Sidhu?

“It means you’re a musician’s musician, so that’s good,” he quips. 

Sidhu may be to proteins what Jimi Hendrix was to electric guitar but, for most people, understanding the significance of Hendrix is probably easier than grasping the impact of a protein expert. 

So what does Sidhu’s work mean to the rest of Canada? 

Producing more antibodies faster 

One of Sidhu’s most significant achievements was adapting a technology known as “phage display” to build vast collections of man-made antibodies that could revolutionize medicine. Sidhu, who is also a professor in the department of molecular genetics, is already putting his tools to good use through the Donnelly-based Centre for Commercialization of Antibodies and Biologics (CCAB), part of U of T's Banting & Best Centre for Innovation & Entrepreneurship. The CCAB's goal is to turn promising lab findings into future drugs. 

Antibodies help fend off illnesses by spotting and sticking to special molecular shapes, called antigens, on the surfaces of bacteria and viruses. Antibodies can also stick to antigens residing on proteins that drive diseases, and they have been used as medicines to treat ailments such as cancer and blindness. But making antibodies was costly and took a long time, which slowed their development.

Sidhu found a way to use a phage display – first developed in the 1980s as a tool for studying proteins – to actually produce antibodies faster and on an unprecedented scale.

Phage display uses tiny viruses, called phages, as antibody-making machines. Antibodies, like any other proteins, are products of genes. The first step is to introduce into the phages packages of antibody-coding DNA. With recent technological advances, phages can be genetically altered to make countless kinds of antibodies. The researchers then look for an antibody that sticks the most to a given disease antigen. The goal is to find drugs with minimum side-effects by identifying antibodies that bind to, and block, antigens for a specific disease or illness, like cancer cells, for example.

Sidhu began working on phage display at Genentech, a leading drug company in San Francisco. He improved the technology to create a staggering 100 billion different antibody shapes, surpassing what our bodies are capable of and reaching the limit of what is physically possible.

A drug in the clinic by 2018

In 2008, Sidhu left California for the Donnelly Centre in Toronto to be at the forefront of genomics research and use its insights to find medically useful antibodies from the deluge produced by phage display.

“But clever science is only 10 per cent of getting a drug that can cure people,” says Sidhu, who is also senior investigator at the Ontario Institute for Cancer Research. All too often, promising research findings from the lab never make it to the clinic.

“Academics are still thinking that the industry’s job is to make new drugs, and that our job is to discover targets. And a target in the industry is not a target until it is highly validated; people in academia often forget that,” says Sidhu.

This is certainly the case in Toronto, which has struggled to make its name in drug development despite its world-leading biomedical research.

To change this, Sidhu established CCAB to function as a middleman between academia and the pharmaceutical industry. Its mandate is to turn promising antibodies into commercial products for drug companies to further develop and bring to market.

Together with Professor Jason Moffat, also at the Donnelly Centre and senior fellow at the Canadian Institute for Advanced Research, Sidhu co-founded Northern Biologics, a small drug company that will advance four antibodies from CCAB’s current pipeline of 100 molecules.

“The goal is to have a drug in the clinic by 2018,” says Sidhu.

He hopes that further partnerships with industry will ensure CCAB – and U of T – get a bigger share in the emerging market of “biologics,” which are drugs made by living organisms. After all, this is where Frederick Banting and Charles Best developed the first biologic – insulin – in 1921. 

Almost a century later, Sidhu is ensuring Toronto is back in the game.

Jovana Drinjakovic is a writer with the Faculty of Medicine at the University of Toronto.