The synthetic is real
At Concordia’s new high-tech Genome Foundry, robotics, automation and interdisciplinary research are helping make the university a leader in the process of designing and building DNA and biological systems.
“My objective is to make this platform central to what we’re doing at Concordia,” says Vincent Martin, professor in Concordia’s Department of Biology.
Inaugurated in 2017 with the support of a $2.4-million grant from the Canada Foundation for Innovation (CFI), the Genome Foundry is a shared facility housed at the Centre for Applied Synthetic Biology (CASB). The foundry, like the CASB, is the first of its kind in Canada. It brings together interdisciplinary teams from biology, biochemistry, journalism, communication studies and electrical, computer, mechanical, industrial and chemical engineering.
In 2012, Martin co-founded the CASB with Nawwaf Kharma, MSc 16, associate professor in the Department of Electrical and Computer Engineering. Martin and Kharma serve as the centre’s co-directors. “In years to come, we want the Genome Foundry to become a provincial or national platform for people from outside of Concordia to come and build their genomes,” Martin says.
As described on the CASB’s website, synthetic biology involves the genetic modification of micro-organisms in order “to design and build biological systems that are beneficial to society.” While its applications are many, synthetic biology allows scientists to “go outside the boundaries of what nature has handed you and create something that’s new to nature,” Martin says. “A vaccine is an example — fighting infections and pathogens — and producing antibiotics.” Its many other applications include environmental protection, sustainable manufacturing, agriculture and food production.
“A genome is so complicated — it’s made of tens of thousands of genes,” says Martin, who is also Concordia University Research Chair in Microbial Engineering and Synthetic Biology. “It’s a problem that’s way too complex for individuals to figure out, so you need robotics, machines and a lot of computational power. That’s one aspect of the foundry that we’re building up.”
Martin reports that new hire Michael Hallett, a professor in the Department of Biology, will be exploring machine learning and artificial intelligence. “If you generate enough information about how the different parts of the genome work together, you can start making predictions and extrapolating further about specific changes in the genome and what the outcome would be,” Martin adds. “We’re trying to create a system that you can tinker with and generate enough information to make the systems predictable.
Right now in biology we can’t do that. It’s a lot of trial and error.”
That trial and error is where automation, systems and engineering come in. “It’s time to industrialize building things out of DNA,” Martin says. “We industrialized building things of steel, cars, computers. That’s what engineers do. With techniques and methods, they make models, so every time they build a bridge they know it’s not going to fall, every time they build a car they know it’s going to drive properly. Let’s bring that discipline to biology and genomes.
From manipulating computer chips and gears and knobs for a car, we’re actually recreating DNA.”
At the Genome Foundry, research by Aashiq H. Kachroo, assistant professor in the Department of Biology, is doing just that. His work attempts to engineer human biological systems “in simple cells like baker’s yeast,” research that could be applied to “understanding basic biology such as evolution and applied sciences like fighting disease,” Kachroo explains.
He came to Concordia in 2017 and his research focuses on humanizing genetic systems in yeast. “Where I think we can excel is to use the Genome Foundry to build human biological systems, not just one gene but multiple genes,” he says. “What we’ve done so far is replace one human gene at a time. That is where the challenge is: can we build larger complexes? Some of these are 30 to 40 genes at a time and we can use the foundry to assemble and build those systems. The foundry will be immensely useful because it has robots, so we can do the process significantly faster and on a much larger scale.”
The scientists agree that such speed offers many advantages. David Kwan is assistant professor in the Department of Biology and affiliated with the CASB and Centre for Structural and Functional Genomics. He says the foundry’s automation allows researchers to potentially conduct thousands of experiments at the same time. That’s much more quickly than the traditional method of “doing it by hand on the bench,” explains Kwan, who arrived at Concordia in 2016. “This takes a lot of the monotonous and repetitive labour away from the research, and frees up researchers and students to come up with new ideas and ways to apply these techniques and approaches.” That will in turn benefit the “broader aims” of the research experiments, he adds.
“Engineering strains is a considerable effort that involves much trial and error,” says Steve Shih, a CASB researcher and assistant pro- fessor in the Department of Electrical and Computer Engineering. “You build the circuit and then you test the circuit. With the cell, we have to go into the code, test the cell, see if it’s what we want and, if not, we’ve got to go back and rewrite the code. With all the equipment we have, the Genome Foundry helps us automate this process.”
Bridging the gap
The foundry also encourages collaboration. “I’m trained as an interdisciplinary scientist and having a genome foundry promotes that,” says Shih, who also joined Concordia in 2016. “We’re bridging the gap between engineering, biology, chemistry and physics; all these science and engineering fields are coming together in this foundry. Beside me I can talk to a biologist or, if I had a question about chemistry, someone would be there. It’s a nice little hub where all these scientists can come together, a really special place.” He also says the foundry is great for collaborations, citing a new DNA writing project on which he, Kwan and Martin are beginning to work.
Kwan agrees. “Having a place to gather minds from different disciplines and sharing these kinds of resources, cool toys and high- tech instruments is really conducive to collaboration, getting people together and co-operating,” he says.
One example is another joint effort between Kwan and Shih. Their infrastructure project combines engineering and biology to develop small, hand-held automation technology. “Specifically, we’re looking at sugars that are related to cancer,” says Shih.
Beyond their shared work, Shih’s areas of interest include biofuel production, trying to understand the genetics behind cancer and expediting the synthetic biology cycle.
Research at his microfluidics laboratory has applications for health and energy.
“Microfluidics are essentially a lab-on-chip technology,” he explains. “The traditional scientific laboratory contains benches, beakers, with a bunch of scientists working away and doing all these experiments. Now, think of miniaturizing all that onto a credit card-shaped device. By doing that, we can integrate all the biological or chemical processes that go on in those laboratories on a miniaturized scale.
When I was in the lab, I used to try to do one, maybe two experiments at one time. But now, with this device, you’re capable of doing thousands. And if you’re really good, if you’re really clever with your designs, you can do millions of experiments at once.”
The miniature scale of microfluidics offers other advantages. “For example, by going to that scale we can track and analyze cancer cells and see what’s going on genetically with them.
We’re currently writing up a publication where we could go into a cancer cell and knock out specific genes related to cancer and prevent the growth of those cancer cells,” Shih says.
Using microfluidics to ex- pedite the synthetic biology cycle is another application, one of which he’s particularly proud. “We would engineer a cell, meaning we would go into the cell and write or modify specific DNA code so it could produce valuable products like biofuel, pos- sibly biochemicals, or even novel therapeutics like specialized antibiotics,” he says. “If you want to create a specific drug from a bacterial cell, there are just so many variations in the genetic code, three billion or so. Imagine your boss tell- ing you, ‘Go in there and try to find the perfect combination.’ That would be impossible!” he says. “We’re using microfluidics to try and automate that process.
Ideally, to quickly go through all the different combina- tions such that it is easy and possibly could be done in less than a day or two.”
As for Kwan, his synthetic biology interests include such questions as, “Can we en- gineer biological systems to produce medicines? Biofuels? Biorenewables? Or common products like plastics, which by conventional means are not produced sustainably?”
His focus is on fine-tuning proteins, to “hone them into precision tools.” That involves protein engineering centred on enzymes that, he explains, are proteins catalyzing chemical reactions. “These are proteins encoded in genes that came from nature, and that evolved in nature to do something else, to help the organisms they come from survive,” he says. “We can try to copy what nature does and try to do evolution in the lab to perfect these proteins as parts of our synthetic biology systems. This involves making changes to genes that encode these proteins, in order to evolve the proteins.”
Martin anticipates that the next big step in the international field of synthetic biology might be to synthesize the human genome. He references a major research project out of the United States called the Genome Project-write, or GP-write. “They’re trying to do ‘the grand challenge’ of the human genome sequence, to actually synthesize the genome from scratch,” he says.
“The ‘grand challenge’ is how to do this: the technology, the ethics — all of that.”