Faculty of Medicine

A More Powerful Way to Develop Therapeutics?

Jul 21, 2016
Author: 
Heidi Singer

A University of Toronto scientist has developed a new method for identifying the raw ingredients necessary to build ‘biologics’, a powerful class of medications that has revolutionized treatment of diseases like rheumatoid arthritis and some cancers.

Associate Professor Philip KimAssociate Professor Philip Kim

Biologics are a type of drug that results from the high-tech manipulation of our own proteins, as opposed to more traditional drugs built from synthetic chemicals. Because of their success so far, scientists are racing to create new biologics – and now, a University of Toronto researcher has developed a way to make that process more powerful.

Philip M. Kim, an associate professor in U of T’s Donnelly Centre for Cellular and Biomolecular Research, combined high-tech computer simulation and high-throughput laboratory experiments to create what he hopes will be the most effective way to discover the proteins that are key to new biologics. His research was published online in the journal Science Advances on July 20, 2016.

“A large fraction of new therapeutics these days involve engineered proteins that latch onto a drug target, for instance on a cancer cell,” says Kim, also of the departments of Molecular Genetics and Computer Science. “Finding a protein that effectively binds to a target can feel like looking for a needle in a haystack. Our method should open up new opportunities to find those key proteins – and make a major impact on the development of new biologics.”

Under the traditional approach to developing a biologic, researchers identify a protein of interest and then test billions of variants, either randomly generated or from a natural source, hoping to find an effective binder. But these methods allow very little control over where and how the protein performs this crucial function on its target – a major factor in its effectiveness.

Kim and his team took a different approach. They used a computer to simulate the binding process, and then designed proteins that would work on the target. This type of theoretical approach has been in development for several decades, but is still not effective enough. So Kim combined the best of both methods. Instead of randomly creating massive libraries of variants, as with the traditional approach, he used computer modelling to generate a smaller, but intelligently designed repertoire of variants. Designing each variant allows for the tight control of all its properties, in contrast to conventional approaches.

“We showed that this method gives you binders that are somewhat stronger than what you get with the conventional approach,” says Kim. “The much smaller library also solves many technical problems, and we can screen for new, previously unscreenable, targets. It’s a very exciting time for cancer research, and for biologics.”

For Kim, the next step is to produce proteins that are important to certain types of cancer, but have not been screened before due to the difficulty producing them. 

Oct 17 "Roots Calling" Film Screening and Dialogue
Other | 5:30pm–7:30pm
Oct
18 – 19
Urology Update 2019
Conference | 7:00am–5:00pm
Oct 18 Oncology Continuing Education Rounds: Dr. J. Feld on HCV and HCC Surveillance Strategies
Grand Rounds | 8:00am–9:00am
Oct 18 Everyday Gynaecology: The Management of Common Gynaecologic Conditions
Conference | 8:00am–3:30pm
Oct
21 – 24
New and Evolving Academic Leaders (NEAL) Program
Course | 8:00am–5:00pm
Oct 23 CIHR Town Hall
Other | 2:00pm–4:00pm
Oct 24 2019 Canada Gairdner Award Laureate Lecture
Symposium | 9:00am–1:00pm

Tweets

UofT Medicine
@uoftmedicine
RT : For our migration issue, we asked 100 members of the community what city they were born in. Their answers spa… https://t.co/AHbd4m7bUb
UofT Medicine
@uoftmedicine
RT : Happy International Pronouns Day! She/Her/Hers. He/Him/His. They/Them/Theirs. Calling people by the correc… https://t.co/jto3QkZjiu
UofT Medicine
@uoftmedicine
RT : How does the flu actually kill people? The short and morbid answer is that in most cases the body kills itself by t… https://t.co/KxiPhLJBoi

UofTMed Magazine

Have we lost the art of dying?

Sign up for your free digital copy.