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Tweaking molecules

How Concordia’s work in synthetic biology could change your life
October 16, 2019
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By Daniel Bartlett

Tweaking molecules The university has a unique combination of resources to be a world leader in the emerging field of synthetic biology.

When Brandiff Caron received a grant from the Social Sciences and Humanities Research Council of Canada (SSHRC) to work with graduate students at Concordia’s Centre for Applied Synthetic Biology (CASB), he noticed an interesting pattern during his interviews.

Looking at how the social, ethical and legal implications of the students’ work entered into their lab experiences, the assistant professor at the Gina Cody School of Engineering and Computer Science and associate chair of the Centre for Engineering in Society asked each of the researchers to define synthetic biology.

“You’ll get as many answers to that question as individuals you ask, even from those who identify as people working in synthetic biology,” Caron says.

While a general definition may remain elusive for the emerging field, the consensus among Concordia researchers is that synthetic biology is the process of engineering novel biological systems to achieve specific functions that do not exist in nature. It’s a nascent, interdisciplinary field that brings together experts in biology, chemistry, engineering, mathematics and physics.

It’s also a research area where Concordia has emerged as a leader. The university is home to the Synthetic Biology Applications program (SynBioApps), Canada’s first Collaborative Research and Training Experience program, as well as Canada Research Chairs in Synthetic Biology, Bioinformatics Algorithms and Microbial Genomics. Investigators at the CASB also include Concordia University Research Chairs in Microbial Engineering and Synthetic Biology, and Optical Bio Microsystems.

A powerful combination of human and physical resources support Concordia’s significant role in the field. “All of this has built momentum where you hire a lot of new scientists, build new infrastructure and have a training program that attracts good students,” says Laurent Potvin-Trottier, assistant professor in the Department of Biology. “If you have good students, good scientists and good infrastructure, then you get good science.”

Steve Shih, assistant professor in the Department of Electrical and Computer Engineering Steve Shih and his team created a system to better find genes related to cancer and destroy them.

‘Immediate and obvious health benefits’

By turning biology into instruments and tools researchers can harness to achieve particular aims, the field has the potential to replicate systems that are of value to individuals around the world.

Caron notes that one of the most obvious areas where synthetic biology research provides major benefits is medicine.

“Once we can figure out how to replicate what happens naturally, we’re no longer reliant on often unsustainable and scarce naturally occurring resources,” he says. “The specific source for things like insulin and medications that have been around for a while are more precarious than people often realize.”

At Concordia, researchers are already demonstrating how their work can have extensive effects.

Steve Shih, assistant professor in the Department of Electrical and Computer Engineering, and his team at the Shih Microfluidics Laboratory created a system that integrates the automation of complex biology experiments to find genes related to cancer and kill them before they develop into the disease.

Meanwhile, David Kwan, assistant professor in the Department of Biology, focuses on using techniques in synthetic biology as a means of exploiting enzymes and developing them as tools that can help to produce therapeutics, bioplastics and biofuels.

Furthermore – where specific enzymes are related to diseases – Kwan and his team have devised new methods to identify drugs that target them within pathogenic microbes or tumour cells. This research could play an important role in fighting infectious diseases and cancers.

Kwan recently received a Petro-Canada Young Innovator Award for his exceptional research achievements at Concordia.

“Our ability to be able to synthesize these things has immediate and obvious health benefits to everyone,” Caron explains.

Beyond medicine, Caron says synthetic biologists can also significantly alter how we manufacture and synthesize materials like plastic so they can degrade more easily yet fulfill the same functions.

“Plastics come from naturally occurring and scarce resources as well – like oil and fossil fuel products,” he says. “There again, we can easily replicate what happens naturally, but change it to avoid some of the negative effects that we’ve become aware of and to replicate many of the positive effects.”

Foundations before applications

One place where Concordia is developing innovative research in synthetic biology is at the Potvin Lab. Led by Potvin-Trottier, who joined Concordia in August 2018 after completing a postdoctoral fellowship at the California Institute of Technology in Pasadena, the lab’s team builds circuits from biological components to better understand how they function.

“One of the things I’m doing is trying to engineer robust biological clocks,” he says. “We use technologies like microfluidics, which allow us to monitor precisely how these clocks work. This has been pretty successful as we made really good clocks. We engineered them in bacteria and they were so robust that we could have these bacteria colonize the gut of mice and the clocks would still oscillate.”

Through their research, members of the lab aim to learn more about the structural elements of biological oscillators so they can develop new systems that may be applicable in the future. The focus remains on the fundamental side of synthetic biology, though Potvin-Trottier identifies areas where the project’s findings could have lasting effects.

“One of the long-term applications, for example, would be periodic drug delivery,” he says. “Instead of having to take a drug every six hours, you would get a microbe in the gut that produces the drug at six-hour intervals.”

For first-year PhD student Giselle McCallum, the idea of trying to build models of existing biological systems is what drew her to the Potvin Lab. She recalls taking a year off after her master’s degree to look for a Canadian university that aligned with her research interests.

Her search proved difficult at times.

“I found many schools focused on biomedical research or applications in synthetic biology, which is great but wasn’t what I was looking for,” McCallum explains. “Then I came across the website for the Centre for Applied Synthetic Biology and I found Steve Shih’s lab, David Kwan’s lab and Laurent’s lab, and I thought this is exactly what I want. I talked with Laurent and it seemed like a good fit.”

Giselle McCallum Giselle McCallum

Today, McCallum is working on the biological oscillator project. The aim of her portion of the research initiative is to have a system that will oscillate with the period she wants no matter what condition she grows the cells in.

Like Potvin-Trottier, McCallum also recognizes ways in which her work could affect people’s lives. She uses artemisinic acid – a precursor to an anti-malarial drug – to illustrate her point. Synthetic biologists engineer yeast to produce the compound to avoid extraction from its natural plant source.

“Future goals would be to actually apply this to something like periodic drug delivery by using engineered probiotics, for example. Or utilizing these clocks to control microbial metabolism and improving the production of useful compounds in synthetic biology, such as artemisinic acid,” she says.

“There are quite a few potential applications, but for now I’m focused on the more fundamental aspects of the project.”

Genes and critical biological processes

Located on the same floor as the Potvin Lab in the Genomics Building (GE) on the Loyola Campus is the Kachroo Laboratory. Led by Aashiq Kachroo, assistant professor in the Department of Biology and Canada Research Chair in Systems and Synthetic Biology, the group is interested in repurposing model organisms by replacing human genes in yeast and other simplified cells.

Currently, the team is investigating whether all essential yeast genes are replaceable by their human counterparts. “All organisms on Earth share a common ancestor, which means we share many genes despite billions of years of separate evolution. Our work focuses on understanding a fundamental question in biology: Are shared genes functionally equivalent?” Kachroo explains.

“We have finished the humanization of all essential genes and have shown that approximately 40 per cent of shared human genes are still swappable in yeast.”

Kachroo’s interest in synthetic biology started during his PhD studies at the Indian Institute of Science in Bengaluru, India. There, he worked on a system in bacteria that, when mutated, utilizes one of the most abundant carbon sources in the world, cellulose.

“I figured that if we engineered the bacterial strain to degrade this carbon source, we would help solve the energy crisis that our planet is facing,” Kachroo says. Since then, Kachroo has shifted his focus toward critical human genes and how they are involved in essential biological processes. His research could have far-reaching effects since any mutations that alter the function of proteins encoded by these genes often lead to human diseases.

“We engineer these shared biological processes in simplified cells like budding yeast,” Kachroo says. “Thus, using evolution to guide synthetic biology, we make surrogate strains that resemble humans at the molecular level. This allows us to study these processes in isolation, asking questions like how the disease is manifested at the cellular level and what needs to change to revert the disease phenotype.”

For Kachroo, joining Concordia in August 2017 had a lot to do with the university’s clear mission and focus on synthetic biology. He appreciates the faculty’s new members and the university’s aim to recruit the best of the best.

“We also house the only Genome Foundry in Canada, with access to state-of-art robotics to scale up the synthetic biology projects,” he says. “Concordia has the best resources available to train young enthusiastic students in synthetic biology.”

Aashiq Kachroo, assistant professor in the Department of Biology Aashiq Kachroo, assistant professor in the Department of Biology.

Ethical, equitable and social impacts

Despite some of its more obvious benefits, synthetic biology is not without its critics.

At the Centre for Engineering in Society, Caron works as the in-house ethicist for the Gina Cody School, as well as for the CASB. He is not an apologist for synthetic biology and approaches the field from an extremely critical perspective.

“There are tons of highly problematic practices taking place under the synthetic-biology umbrella that are unethical by any practical standard,” Caron says. “Take things like designer babies. It’s no longer a consideration to think about them as a future possibility – it’s very much possible now.”

Citing popular Hollywood films like Jurassic Park and Gattaca, he notes that synthetic biologists can create life out of non-life, which carries both positive and negative implications. Still, Caron describes the field as a work in progress.

“Given synthetic biology is in a nascent stage, we have a rare opportunity to organize a field of study consciously and reflectively,” he says. “What the field itself is trying to do is think about how to best self-regulate.”

Caron explains that one of the over-arching aims of creating a selfregulatory body is to get experts to work across all kinds of differences, including national frameworks. He uses the profession of engineering in Canada as an example that synthetic biologists might consider as they attempt to move toward self-regulation.

“The professional system set up in Canada in the mid-’70s requires that professional engineering be structured in a specific way, but that the actual regulation of it is done by engineers themselves,” Caron says. “The government isn’t coming in and saying here’s what engineers need to do. They’re saying engineers need to decide what engineers need to do.”

At Concordia, Caron has developed a technology-assessment method that encourages undergraduate students to recognize the ethical, equitable and social effects of their capstone projects. He has since used it with Concordia’s International Genetically Engineered Machine (iGEM) team and is happy with its results.

Despite this, Caron admits that it is still sometimes challenging to get engineers and scientists to think seriously about the ethical implications of their work. He describes how many experts think they are immune to the social problems that could arise from their research because they are only making the technology, not carrying it out.

“It’s difficult to get students’ intuitions flowing around this stuff, but synthetic biology can be a good way to do it because it’s easier to see the potential problems,” he says.

“The unique structure of how issues of technology and society are dealt with in the Gina Cody School has afforded us great opportunities to promote some really awesome, cutting-edge research and the best ways to incorporate ethical, legal and social implications of science and technology into the actual classroom.”

Closing the gender gap

Even though there are more female scientists entering synthetic biology than other science, technology, engineering and mathematics (STEM) fields, Caron is quick to note that they are still in the minority.

Nevertheless, he sees hope for the future. “In a bunch of parts of the world with different cultures and gender norms, there are actually more women in STEM fields than there are men,” Caron says.

“There’s a lot of hope because there’s a possibility that makes considerations around gender more easily put into practice than they would in these other fields with more entrenched traditions.”

For McCallum, choosing to work in synthetic biology has a lot to do with her experiences interviewing for positions in labs. Because the field is still new, she notes that many principal investigators are young and thrilled to share their passion with students.

“I don’t know if I just picked good labs to work in, but all my supervisors were super enthusiastic to have me there,” McCallum says. “They’re very excited about their field and really want to teach the upcoming generation of students about their research. I think that’s what pulled me into this field. Why wouldn’t I work where somebody is eager to teach me about the things that they love?”

What advice does McCallum have for future scientists who want to pursue research in synthetic biology?

“It’s useful to explore different fields early on because of the interdisciplinary component. You can always learn new areas while you’re working in synthetic biology, but it’s helpful to have fundamental skills and understanding in biology, chemistry, engineering and mathematics,” she says.

Caron agrees and says Concordia is an ideal place to pursue such research, given the existence of the CASB and its close relationship with the Centre for Engineering in Society.

He also sees students benefit from access to Canada’s only Genome Foundry, as well as Concordia’s involvement in co-founding a new Global Biofoundry Alliance with 14 other institutions.

“It’s probably the best place in Canada to engage in this kind of research seeing as the Centre for Applied Synthetic Biology is the first and still only research institute of its kind, and the Centre for Engineering in Society is a unique model that houses social scientists within the Gina Cody School.”

Equipment and researchers at Concordia’s genome foundry. Concordia’s genome foundry is the only one of its kind in Canada.


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