Turning to science: Two C150 researchers pave the way for self-driving labs and a life-saving fentanyl vaccine

Alán Aspuru-Guzik and Borries Demeler are among the two dozen Canada 150 Research Chairs (C150s) announced in celebration of Canada’s 150th anniversary. Both scientists left the United States to relocate to Canada, and seven years on, both credit the new partnerships they’ve forged here for exciting breakthroughs in their respective fields of chemistry and biophysics.

It was all made possible by the Government of Canada’s $117.6 million investment to enable the country’s universities to attract top-tier, internationally based scholars and researchers to Canada.

Aspuru-Guzik was a professor at Harvard University before moving to the University of Toronto. As the C150 in Theoretical and Quantum Chemistry, he established the Matter Lab. Its mission has been to accelerate the discovery of new chemicals and materials useful to society by leveraging quantum computing, machine learning and automation.

“The university has backed me and my vision, so it's a great place for me to be,” Aspuru-Guzik says.

Demeler, the C150 in Biophysics, came to the University of Lethbridge in Alberta from the University of Texas medical school in San Antonio as an expert in the analytical ultracentrifugation (AUC) technique. At Lethbridge, he established the Canadian Center for Hydrodynamics, a research centre offering comprehensive solution characterization services for scientists studying nanoscale molecules.

“I’ve never regretted it one second,” Demeler says.

Aspuru-Guzik: “I believe science at the interface is where the action is.”

Growing up in Mexico City, Aspuru-Guzik was a curious kid who read encyclopedias for fun and became deeply—and equally—interested in chemistry and computer science. Trying to decide which field to pursue academically was difficult.

“I basically flipped a coin,” he says. He ultimately earned a PhD in physical chemistry from the University of California, Berkeley.

“Then, when I was at Berkeley [as a postdoctoral fellow], I was able to figure out how to do quantum computing for chemistry—how to use quantum computers instead of classical computers to simulate chemistry,” he explains.

Aspuru-Guzik continued to push the boundaries of chemistry all the way to his current position, as a world-leading scientist and pioneer in clean energy materials, computational chemistry, quantum computing, artificial intelligence (AI) and autonomous experimentation.

“I’ve been quite lucky in identifying new fields first,” Aspuru-Guzik says. “I believe science at the interface is where the action is.”

When the opportunity arose for Aspuru-Guzik to move to Canada as a C150, Toronto’s cultural diversity appealed to him. He himself has an international background: he was born in the United States but grew up in Mexico.

“Toronto is a great city for somebody like me,” he says.

At the University of Toronto, Aspuru-Guzik’s rapidly growing Matter Lab includes 45 researchers (up to about 60 including undergraduate students) from a variety of backgrounds. They work at theoretical chemistry’s interface with physics, computer science and applied mathematics. Aspuru-Guzik says they are hungry for new ideas—for approaches that can be disruptive to the field.

“I think it's well known as a very creative group, because I hire people from many, many disciplines. The difference between the Matter Lab and other labs is that I can have a chemical engineer, a chemist, a computer scientist and a physicist tackling a problem in the same room,” he says.

The newest additions to the room are robots.

In 2022, the University of Toronto received a prestigious grant for nearly $200 million from the Canada First Research Excellence Fund. Aspuru-Guzik would come to serve as director of the Acceleration Consortium to pursue the concept of a “self-driving” lab.

Aspuru-Guzik has been working on the idea of self-driving labs since 2017, when he co-organized a brainstorming conference in Mexico City. He sees it as a way for chemists to save time and money, while making even more discoveries. In contrast to traditional labs, a self-driving lab would have an AI program choose the next experiment to run, using its predictive power of what will work, and analyze the data. This could lead to the discovery of new materials and molecules in a fraction of the usual time and cost.

The size of the $200 million investment speaks to the immense opportunity self-driving labs present. They could usher into existence everything from life-saving medications and biodegradable plastics to low-carbon cement and renewable energy.

A more sustainable future is a major motivator for Aspuru-Guzik. He is currently pursuing research to turn oil sands bitumen into organic batteries and is also working on methods for the recycling of consumer plastics.

“Those are the kinds of things I think about every day,” he says. “What can I do with my technology that can make a difference?”

Demeler: “That was a game changer, right there.”

Demeler is putting the University of Lethbridge on the map as a hub for AUC. The sophisticated scientific technique was once nearly lost to the history books. AUC works by spinning samples in an ultracentrifuge at extremely high speeds that cause molecules to separate. With the help of several optical detection systems, AUC can give information about a sample’s size, shape and interactions.

Demeler was first introduced to the technique as a graduate student at Oregon State University in the late 1980s. A professor and mentor impressed upon him the value of the technique. But, its main application at the time—measuring the mass of proteins—was rapidly losing ground to a new method that was faster and cheaper: gel electrophoresis.

“Before you knew it, AUC was essentially eliminated from the research sphere. It was pretty much gone,” says Demeler.

Still just a student, he saw a way to help: by digitizing the 40-year-old instrument.

“I went to the professor and said, ‘Look, I have an idea. Let's digitize this instrument so we can use a computer to do much more sophisticated data analysis and expand the technique to many new applications.’ And that was a game changer, right there.”

Demeler succeeded in his mission and went up and down the West Coast of the U.S. digitizing the instruments for others. He then created UltraScan, an open-source, multiplatform software suite that analyzes the AUC results.

“I've never commercialized anything, including my software. I’ve always given everything away for free, and even put my software on GitHub, where everybody can download it, look at the source code, improve it and work with it,” Demeler says.

This open-source software exchange has helped bring about an AUC renaissance.

Today, scientists use AUC to understand complex molecular systems. Its use has advanced development of pharmaceutical drugs, and provided insights into influenza, HIV and Alzheimer’s disease.

At the University of Lethbridge, Demeler is eager to collaborate and find even more applications for AUC. One partnership he initiated with the University of Montana (UM) is making headway on one of the most serious health problems currently facing North America: the fentanyl epidemic, which has caused a surge in fatal overdoses across Canada and the U.S.

Early on in his C150 role, Demeler approached UM’s Center for Translational Medicine—which has a renowned drug discovery and development program—and offered to run early tests on the University of Lethbridge’s AUC instruments to help develop a fentanyl vaccine. The University of Montana saw positive results in those early tests, and the drug has now made it as far as clinical trials. It could be on the market in 2028, if all runs smoothly.

“It’s quite amazing,” says Demeler. “You can essentially eliminate fentanyl with that vaccine before it does any harm in the brain.”

Demeler is also passionate about teaching. He sees it as critical to ensuring AUC, which he has dedicated his career to, lives on.

“If I don't disseminate it, it was for nothing. So, it behooves me to really go out there and teach this to other students, practitioners, companies, you name it, whoever wants to buy that machine,” Demeler says.

The quality of his students and lab at the University of Lethbridge gives him hope.

“We have a wonderful new building, with wonderful laboratory conditions,” he says. “We have this shared environment here where my colleagues in the department and I share the entire lab space, which encourages the students to work together. Every day, there’s something new.”

Demeler’s team has travelled to global conferences to share what they’re working on, going as far as Demeler’s native Germany.

“One of my efforts here has been, let’s put Lethbridge on the map,” he says. “I’m always proud to represent Lethbridge. In 2022, we organized an international AUC conference here with over 100 participants from 16 countries.”

That effort, too, is paying off.

“When I go to a university or conference to give a talk, these folks, they’re very familiar with Lethbridge now,” he says.

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Keywords

• Theoretical and Quantum Chemistry
• Quantum computing
• Machine learning
• Fentanyl epidemic
• Analysis
• Biophysics
• Open-source
• Artificial intelligence
• Vaccine
• Sustainable future
• Drug discovery and development