NAthan Braniff - July 15, 2019

Monday morning at Waterloo SynBio 4.0. Photo courtesy of @Synbiosymp and WCMR.

Over the past three years the SynBio symposium series hosted at Western University (see our summary from last year here), has served as the primary academic venue for Canadian synthetic biology. This year, the conference significantly expanded with SynBio 4.0 hosted at the University of Waterloo, with the format moving from a one-day to three-day event (May 26-28). This year SynBio 4.0 featured researchers from a variety of Canadian academic institutions and companies, and for the first time, included a day dedicated to student-focused workshops. Here we summarize the conference activities, giving a snapshot into the diverse range of synbio research being undertaken across Canada.

Student Workshops and Panels

The first day of the conference was student focused, with workshop talks on a variety of key synthetic biology disciplines, as well as panels on the Canadian biotech industry and educational programs. The morning workshop session featured talks by Laurent Potvin-Trottier (Concordia University) on the use of mathematical models in engineering biological systems, and David Kwan (Concordia University) on the current state of protein engineering. This was followed by an industry panel featuring representatives from several Canadian companies in the biotech sector namely; Dave Conley of Aquabounty Tech., Leo Wan of Ranomics, Graham McKinnon of Carbon Patent Group, and Kevin Chen of Hyasynth Bio. The panel discussion covered a wide range of issues including approaches to networking and breaking into the industry, management of intellectual property for young companies, as well as advice on moving from academia towards founding a startup. 

The afternoon workshops featured David McMillen (University of Toronto) who discussed strategies for designing synthetic regulatory circuits, and Kaushik Venkatesan (University of Toronto) who presented techniques for building more productive strains in biomanufacturing. This was followed by the afternoon panel on Canadian synthetic biology education. The panelists included Jason Grove (University of Waterloo), Kathleen Hill (Western University), Mads Kaern (University of Ottawa), Orly Weinberg (Concordia University). Kaern emphasized the need for a student-driven change in the way synthetic biology research and education are managed in Canada, and lamented the limited Canadian progress made in the past decades. 

“Synbio is more about putting things together, not taking things apart, which does not fit well in traditional science departments.”

— Mads Kaern

The education panel from SynBio 4.0, featuring (left to right) Kathleen Hill, Orly Weinberg, Jason Grove and Mads Kaern. Photo courtesy of Brian Ingalls.

Looking towards the future of synbio education in Canada, Wienberg gave a summary of current efforts at Concordia to construct synthetic biology focused curricula. These efforts in expanding synbio education are complementary to Concordia’s ongoing investment in its gene foundry. Similarly, Hill discussed efforts to launch synbio training programs at Western, and the various approaches to synbio education overall. Notably, these new programs at Western were initiated because of strong student support starting three years ago, in part thanks to the efforts of our Steering Committee member Samir Hamadache, and others involved in the student-driven Western Synthetic Biology Research Program. Grove compared and contrasted science and engineering, arguing that synthetic biologists are primarily engineers, due to the application focus of the field.

Post-panel discussion and questions highlighted several key needs:

•  The need for synbio-focused degree programs. There are currently no synbio-focused degree programs offered at any Canadian institution.

• The strong need for funding of synbio education, lest Canadian research and companies fall behind international competitors due to a lack of skilled personnel. 

• The need for a clear definition of the skill sets to be taught in these programs, with input from industry as well as researchers. Defining the balance between fundamental skills and specific applications is a core challenge.

• The need for investment and program development to scale with the growth of the Canadian biotech sector, so that graduates can transition efficiently to industry positions with a skillset matching industry demand. 

•  The need for an education plan for the future. The biotech landscape is highly diverse and rapidly changing, it is difficult to find a one-size-fits-all solution in a single program. Planning is needed in order to offer an appropriate mixture of application specialties and graduate/undergraduate programs in a coordinated manner.

Research Talks Day 1

Conference organizers Valarie Ward, Brian Ingalls and Trevor Charles kicked off the first day of the research talks with opening remarks and introductions. Ned Budisa (University of Manitoba) gave the first keynote address, describing his groups efforts to expand the usable genetic code beyond the standard 20 amino acids. Working within this emerging subdiscipline of xenobiology, they are building the synthetic translational machinery necessary to re-code nature so unnatural or noncanonical amino acids can be included in proteins produced by engineered cells. This work has applications in protein production and bio-manufacturing, and Budisa specifically highlighted a project to produce wet-binding, bio-inspired adhesives. He noted his group is currently looking for motivated graduate students and postdocs. 

The keynote was followed by a report from Bettina Hamelin. She highlighted Ontario Genomics current efforts to promote synthetic biology within the province and across the country, answering the dual questions; “Why synthetic biology and why now?”. Ontario Genomics envisions a three tiered plan for SynBio growth in Canada;

1. Establish technical capacity -- including the creation of genome foundries and the training of the necessary technical staff.

2. Create funding programs -- initially focusing on sandbox grants for disruptive projects to ‘feel’ out the tri-council, with the eventual goal of having flexible, phased-funding with a rolling-intake cycle. 

3. Write a Canadian SynBio strategic plan -- following similar documents published by other countries like the U.S., U.K., Singapore, and Australia. 

Ontario genomics is currently collaborating with other provincial and national organizations to create a SynBio Steering Committee to work towards the above goals. Hamelin concluded by saying:

“This is all about collaboration, we are too small a province - as a country we are small - collaboration is key because greatness happens together.”

— Bettina Hamelin

Adam Radek Martinez delivering his (award-winning) research talk at SynBio 4.0. Photo courtesy of @Synbiosymp and WCMR.

Afternoon talks saw discussion about the harnessing of novel wild microorganisms and the engineering synthetic ones for bioproduction. Kenza Samlali (Shih Lab, Concordia University) presented work on the development of novel gene editing and biosensing on microfluidic chips. Kenza’s talk won the best graduate student presentation competition, which was sponsored by Carbon Patent Group. Other student talks featured many topics, including novel mitochondrial and genomic editing protocols, bioinformatic tools for engineering insect resistance and the use of engineered optogenetic tools for probing developmental pathways. 

Adam Radek Martinez (Charles Lab, University of Waterloo) won best high-school/undergraduate talk for his work on the engineering of novel silver biosensors. The afternoon also featured a poster session, Sam Slattery (Western University) took home the poster prize for his work on a plasmid-based toolbox for Cas9-based genome editing.

Research Talks Day 2

The SynBio 4.0 poster session featured a diverse range of synbio research from Canadian institutions. Photo courtesy of @Synbiosymp and WCMR.

The second day of research talks began with a keynote from Wei Zhang (University of Guelph). His group has been working to make protein-protein interactions more engineerable, specifically focusing on the human ubiquitin signalling pathway. This work has a broad array of applications to human health, including the treatment of viral infections and better understanding of signalling pathways involved in cancer. The second day also saw many exciting talks from student and post-doctoral researchers, covering topics such as the development of mathematical and bioinformatic models, the engineering of bacterial-plant signalling for the coordination of nitrogen fixation, and the construction of modular, multi-host large-fragment cloning vectors.

The day concluded with an industry talk by Michael Pautler (Vineland, Platform Genetics), who discussed the current need for Canada-specific breeds of high-value horticultural crops. Currently Canadian growers use breeds that have been created specifically for European climates, and which underperform when grown here in Canada. While Vineland currently uses traditional breeding technologies (i.e. cross-breeding and mutagenesis)  to address this problem, genetic engineering could play a role in helping Canadian horticulture to close this gap in the future. However, Pautler noted no GMO products are currently used in Canadian horticulture for two main reasons; 1) consumer acceptance for the technology is low because of current perceptions of genetic technologies, and 2) there is a high regulatory cost caused by the Canadian regulatory process. Pautler suggested that, in the current economic climate, if genetic engineering was successfully used to create an improved crop, it would be easier to get it approved and sold by randomly regenerating it through mutation then to proceed with the original GMO. This process is obviously inefficient. Paulter proposed addressing the regulatory barriers by standardizing and streamlining the regulatory process to make it more reasonable and efficient. He also suggested a permissive licensing of genome editing technologies would allow for their wider use. With respect public opinion, Pautler emphasized the importance in using the technology to develop crop traits that consumers care about and to clearly communicate benefits and limitations of the technology to consumers and other stakeholders.

Benjamin Scott - June 17, 2019

Dr. Wei Zhang, Assistant Professor University of Guelph

Dr. Wei Zhang is an Assistant Professor in the Department of Molecular and Cellular Biology at University of Guelph (www.thezhanglab.com). He conducted his PhD in the laboratory of Daniel Durocher in the Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital and Department of Molecular Genetics at University of Toronto, where he identified new molecular mechanisms of telomere addition to DNA breaks and the spatial organization of DNA repair. For his postdoc studies with Drs. Sachdev Sidhu and Jason Moffat at the Donnelly Centre for Cellular and Biomolecular Research, Dr. Zhang developed combinatorial protein engineering approaches to manipulate human and viral enzymes controlling critical cell signal transduction cascades for innovative therapeutic strategies. He has received numerous awards, including the 2016 Mitacs Award for Outstanding Innovation, 2017 Cancer Research Society Scholarship for the Next Generation of Scientists, and the inaugural 2018 Donnelly Centre Research Excellence Award. To date, he has published 20 papers in high-impact journals and 3 pending patents. His lab is currently funded by Cancer Research Society, Rare Disease Foundation, NSERC, and CIHR.

How did your interest in synthetic biology first develop?

My interests in synthetic biology developed probably later than most people in the field, around the time when I was finishing my PhD and trying to figure out what I should do for postdoctoral studies. I was focusing on understanding the molecular mechanisms of telomere biology and DNA repair at that time and “synthetic biology” is really not something in my mind, until I started supervising an undergraduate student in the lab (Devin Trudeau, who later did his PhD with 2018 Nobel laureate Dr. Frances Arnold) whose project was synthesizing an artificial telomere. While the project went nowhere, it became clear to myself that my passion is not just exploring the mechanisms that drive cancer progression, rather to use that knowledge to ultimately develop effective drugs. Therefore, I changed my research focus from “understanding” to “modulating” cells signaling with the vision of bridging basic research and translational research by joining the laboratory of Dr. Sachdev Sidhu in the Donnelly Centre. Dr. Sidhu is an internationally recognized leader in protein engineering and phage-display technology. He spent a decade as a principal investigator in the Department of Protein Engineering at Genentech, Inc. He has led the development of phage-displayed synthetic peptide/protein/antibody libraries that have proven to be a rich source of valuable reagents for basic research and potential therapeutics for cancer and other diseases. During my postdoc tenure in the Sidhu lab (and later jointly supervised by Dr. Jason Moffat), I was able to combine the understanding of human cell metabolism to the generation of synthetic drug-like molecules that has potential for treatment of various human diseases. I expect this skill-set to serve as the foundation upon which I can explore my synthetic biology and protein engineering research program in University of Guelph.

About a year ago you started your lab at the University of Guelph. What advice can you impart to new PIs?

For new PIs, there will be many challenges other than the research itself. Here are what I learned from colleagues and mentors in my department and elsewhere. The three most important things are: People, Penny, and Paper. First of all: people. Surely you want to recruit the best to your lab, but that is not always easy and for different roles you need to look for different characteristics (e.g. technician vs graduate student). Here comes the second component of “people”: mentors. A good mentor will be extremely helpful on every aspects of a new PI’s life, including sharing experience in hiring. Please take advantage of every opportunity to broadcast your lab (invited talks, personal webpage, twitter, linkedin, etc.) to let the world know you are out there and recruiting. Second: penny. For a lab to be sustainable, getting competitive operating grant is essential. Start as soon as possible and apply as many as you can. Get support from your PhD and postdoc mentors and obtain suggestions/comments/feedback from people knowing your work and importantly, who are completely outside of your field. Grantsmanship is critical and that only comes to you after many rounds of revision based on suggestions from others. Do remember that sometimes it is good to be stubborn to stick to what you believe is the right way to write but definitely think from a reviewer’s perspective. Meanwhile, start engaging collaboration with other scientists and tap into funding opportunities that you can bring in convincing complementary expertise or become co-PIs and request for budget. Finally: paper. There is no need to further elaborate on this but I want to emphasize that try your best to avoid gap of publication. Instead to show your independence, which is important, it is ok to continue work with previous mentors and collaborators to have a continuous track record of publishing.

Are there specific resources needed to strengthen synthetic biology in Canada? What would make Canada a better place for the field?

Synthetic biology in Canada is booming, thanks to not-for-profit organizations like SynBio Canada, funding agencies like Ontario Genomics, and many other small and big firms willing to invest and nurture this emerging genre. I think Canada has a huge talent pool for the broad field of synthetic biology. In my opinion the value of synthetic biology in translational research is indeed recognized in Canadian public and private sectors. However, to make Canada a better place for this field, one has to realize the importance of conducting basic research for the benefit of synthetic biology, and vice versa. I find that in most cases it is presumable that for synthetic biology research you need/should get match from industry sources and there is a bias about what kind of synthetic biology research we conduct in Canada. There should be more operating grant funding opportunities from government agencies supporting basic research, such as Canadian Institutes of Health Research (CIHR) and Natural Sciences and Engineering Research Council of Canada (NSERC). How about establish an Institute for Synthetic Biology in CIHR? Similarly, “Synthetic Biology” could be a separate Evaluation Group in NSERC Discovery Grant program.

You’ve used phage display technology extensively for your protein engineering work. What makes this technique so useful?

Half of the 2018 Nobel Prize in Chemistry was awarded to Dr. George P. Smith, who invented phage display, and to Sir Gregory P. Winter, who used phage display to evaluate peptide and antibodies for therapeutic purposes.  Needless to say, phage display is powerful and essential for protein engineering. It is very easy to learn and perform the experiments, and quite reliable and efficient in selecting for binders from a library of billions of variants. Other competitive advantages include: 1. Fast and cost-effective production. The whole process takes about 2 weeks and only purified proteins, phage, and E. coli are being used. 2. Highly amenable to rational optimization. The affinity and specificity of selected binders can be further improved. 3. Identification of competitive and allosteric regulation on protein surfaces small molecules cannot reach.

What are some up-and-coming synbio techniques or applications you’re excited about?

I have to give it up to CRISPR. We all witnessed how this technology revolutionized biological research in the past 5 years and it will continue to do so, particularly pertaining to synthetic biology. My lab is also interested in further improving the efficiency and accuracy of CRISPR in genome editing by manipulating DNA damage and repair. I do want to note the importance of ethics in implementing this technology in clinical research, as we heard from Dr. Jiankui He who shocked the world by revealing his controversial human embryo experimentation.

We’re trying something new with our “SynBio Grand Challenges” leader board game. You get 5 points to either add to or subtract from each of these Challenges. -3 points means the challenge is removed, and you can replace it with your own idea! Be ruthless!

Some possible examples: You give +1 point to each, or you give +2 points to two of them and -1 point from one.

The SynBio Grand Challenges Game

• Specific and tunable human gene editing +2, Score = 7
• Carbon neutral chemicals & fuels +2, Score = 4
• “Smart” therapeutics that sense and respond +0, Score = 4
• Multi-host nitrogen-fixing microbes +0, Score = 2
• Microbes for bioremediation +0, Score = 2
• A genetic code that uses new amino acids -1, Current Score = -2

NATHAN BRANIFF - April 4, 2019

In part 2 of our summary of Ontario Genomics’ Canada SynBio 2019 conference, we discuss the investor showcase, the pitch competition, the keynote from Ginkgo’s Christina Agapakis as well as highlights from the final panels and the second day, including an update on Canada’s first genome foundry at Concordia University.

VC Investor Showcase

“Be bold, you want to be the leading company, not just in Canada, but worldwide.”

— Elizabeth Douville, AmorChem

The afternoon session began with the investor showcase, where venture capitalists from the US and Canada gave insight into the biotech start-up ecosystem. The panel featured Sean O’Sullivan of SOSV, Ganesh Kishore of Spruce Capital Partners, Élizabeth Douville of AmorChem and Collin Kelleher and was moderated by Mary Dimou of Canopy Rivers. The panel emphasized the diverse range of companies that the investors have funded, and the many strategic paths to a profitable startup. O’Sullivan noted that “We’ve seen great companies coming out of Canada and we’d love to see more.” Douville, who represents Quebec-based biotech investment fund AmorChem, encouraged biotech researchers to reach out “If you are an academic investigator with a disruptive technology you should come talk to us.” AmorChem focuses on building companies out of academic research, investing early in promising technologies.

FREDsense won first place in the pitch competition, with a cash prize of $25000 and $5000 worth of supplies from IDT. (Photo by Nathan Braniff)

Pitch Competition: Accelerating Startups by Design

The VC investor panel also served as the judges for the Accelerating Startups by Design pitch competition. A new addition to this year's conference, the competition highlighted  six synthetic biology startups who presented for both cash prizes, and laboratory resources courtesy of IDT. Canadian startup FREDsense won first place with its synthetically engineering biosensors for water contamination detection. Quebec-based startup, Tatum bioscience, took second place for its engineering of a reprogrammable CRISPR-based targeting of antibiotic-resistant gut pathogens.

The other competitors included Genecis Bioindustries, Creative Protein Solutions, Spindle Biotech and Metaphage Bioceuticals. Genecis Bioindustries has engineered bioprocesses to produce a bio-plastic precursors, polyhydroxyalkanoates (PHA’s), from organic waste. Creative Protein Solutions has created a diagnostic device using an engineered biosensor for rapid, onsite monitoring of diseases in cattle. Spindle Biotech is building novel DNA synthesis technology, using specialized enzymes and microfluidics to improve performance and decrease costs. Metaphage Bioceuticals is using DNA mini-strings to engineer a novel trans-gene delivery mechanism for gene therapy, this will ideally increase treatment reliability and decrease the time needed for regulatory approval.

University of Guelph iGEM Team accepting first place for the poster competition. (Photo by Nathan Braniff)

In addition to the pitch competition, this year’s conference also featured a student poster competition. The University of Guelph iGEM team took the top spot, with their work to engineer enzymes to degrade “beer stone”, which is calcium oxalate that builds up in the beer brewing process.

Keynote - Christina Agapakis, Ginkgo Bioworks

Christina Agapakis, Creative Director at Gingko Bioworks gave an exciting keynote talk on the companies ongoing work to make biology easier to engineer. Ginkgo has been a pioneer in scaling up bio-engineering, with 50 Mbp of DNA synthesized each month, and individual projects having as many as 20000 distinct enzymes synthesized and tested. Agapakis noted Ginkgo’s strong emphasis on collaboration between their ‘Foundry’, which performs the automated biological lab work, and their ‘Codebase’, containing the antotations and theoretical knowledge needed to guide and expedite new biological designs. While the foundry uses state-of-the-art automation and parallelization to synthesize and test new genetic designs, the codebase contains data on the functions of proteins and specific DNA sequences which allows for rapid sharing of knowledge between projects. This harmonious interplay has led to a bioengineering version of Moore’s law, known at Ginkgo as “Knight’s Law”, named for Ginkgo and SynBio founder Tom Knight. Knight’s law suggests engineering new genetic designs will undergo an exponential decrease in cost in the near future, heralding an important role for synthetic biology in many industries over the coming decades.

“To create a new technology, you are not just engineering the technical part, you’re [also] engineering a social part."

Christina Agapakis, Ginko Bioworks

Agapakis also discussed Ginkgo approaches to public outreach and its strategy for engaging with the public regarding genetically modified organisms (GMO’s).  She suggested the GMO debate is a major hurdle for industrial synthetic biology, and the debate is complex touching on ethics, intellectual property, public policy, philosophy and the very definition of ‘natural’.

As indicated by Ginkgo CEO Jason Kelly’s New York Times Op-Ed, Ginkgo has taken the strategy of fully embracing the label GMO, indicating to consumers that GMO’s are not only safe, but something valuable and to be proud of. In an effort to rebrand and take ownership of the term ‘GMO’, the company has highlighted the unique social value of genetic engineering in projects like ‘Resurrecting the Sublime’. In ‘Resurrecting the Sublime’, Ginkgo used its genetic engineering and bioinformatic infrastructure to reconstruct and synthesize odours of extinct plants, enabling them to create scents that without genetic engineering would have been lost forever. Agapakis suggested outreach projects like this, combined with a policy of transparency, will hopefully prompt people to reconsider the social value of genetic engineering.

Making Biology Easier to Engineer Panel

The final panel of the day focused on general aspect of engineering biology. Panelist Vince Martin of Concordia University discussed the recent opening of Canada's first genome foundry. Martin announced it was already expanding, after only a year or so of operation, with plans to enable engineering of mammalian cell lines in the near future. He also stated that since foundries are becoming so popular, the team at Concordia has been fielding questions from other groups around the world. Because of all this interest, half-jokingly he said that his group had suddenly become experts in running a synbio foundry.

“[We need to] pay attention to the opportunity cost of not exploring a promising field.”

Vardit Ravitsky, Université de Montréal

While the foundry was originally intended primarily for research and training, it was on track to transition to a more accessible service model due to popular demand. Martin suggest the foundry would increase ‘the number of shots on goal’ for SynBio projects in Canada, by allowing for faster and cheaper DNA synthesis. He also discussed the Concordia Foundries participation in the Global Biofoundary Meeting 2019, which will emphasize standardization and inter-foundry collaboration across the many foundries in other countries. Those interested in the Concordia Foundries services should reach out to its administrative team.

Vincent Martin presents on the exciting synbio ecosystem being developed at Concordia University. (Photo by Benjamin Scott)

Vardit Ravitsky (Université de Montréal) discussed the social and political aspects of more widespread engineering of biology. She emphasized that the ethical debate around genetic engineering often neglects the duty to share the benefits of new technologies. She said their is also an ethical obligation to ask ‘why yes?’. There exists a real risk that a useful technology that can help millions of people will not be developed because of fear.  She suggested that a lack of proportional regulation, that balances positive and negative risks, may hold Canada back.

Ravitsky also emphasized the duty of Canadian scientists in public outreach. She urged scientists to speak to journalists often, stating that a fear of misquotation or of speaking outside your expertise is not a realistic excuse; it is a “very real part of your job.” She concluded emphasizing the importance of public outreach, and that realistic, grounded communication about the technology is a good safeguard against sensationalism and fear mongering, and the potential regulatory backlash caused by either.

Up next is a quick rundown of workshops on Day 2!

Nathan Braniff - March 23, 2019

Earlier this month, Ontario Genomics hosted the second annual Canada SynBio meeting in Toronto. The meeting brought together members of the Canadian and international synthetic biology community for a two day discussion of research, business and policy topics related to the rapidly developing field. The event expanded significantly upon last year’s successful conference (summarized here), with a variety of panel discussions, and a pitch competition from start ups.

Several members of the SynBio Canada Steering Committee were able to attend. In this article, we summarize some of the discussions and presentations from the first day, highlighting some of the fantastic synbio research and companies in Canada and abroad.

Keynote - George Church, Harvard University

The first day began with a keynote talk by Professor George Church of Harvard University. He summarized the many recent advances in multiplex genome engineering that his research group has pioneered, including the editing of mammalian cells for virus resistance and in vivo lineage tracking. He also outlined the goals for Genome Project Write (GPW), the multi-national collaborative follow-up to the original Human Genome Project (HPG). The original HPG successfully  sequenced a human genome in 2003, which led to rapid advances in efficiency and cost for DNA sequencing over the following decades. The new GPW, led by those like George Church, will attempt to synthetize a synthetic human genome (in cell lines) over the coming years. The GPW has several contributing members from Canadian institutions. Professor Church discussed the range of potential applications of DNA synthesis technology developed as part of GPW, including developing cryo-stable organs for transplant, investigating cancer and senescence resistance in model organisms as well as engineering viral resistance.

When asked about the potential for misuse of these emerging technologies, Church emphasized the importance for surveillance and biocontainment, as opposed to moratoriums. He also pointed out that applications like human germline editing are not only ethically but also technically difficult, and the technology has many more immediate applications, like making organs more accessible for transplant. These immediate goals have fewer ethical concerns and can be accomplished in the short term with widely distributed benefits to society.

“We have banned the word impossible in my lab.”

Dr. George Church, Harvard University

Human Health and Engineering Biology Panel

Dr. Laura Prochazka (postdoc in the Zandstra lab, University of Toronto/UBC) presents work to engineer stem cells using synthetic biology. (Photo by Benjamin Scott)

The Human Health and Engineering Biology Panel featured discussion of novel health related engineering effort being developed by researchers in Canada. Laura Prochazka (University of Toronto) gave an overview of ongoing efforts to engineer more safe and efficient stem cell therapies using synthetic biology to guide cell specialization. Keith Pardee (University of Toronto), discussed his labs ongoing development of paper-based cell-free biosensors, which have been used to detect viruses like Zika and Ebola. He also outlined his work using synthetic biology to engineer biosensors and on-demand biomanufacturing to address global health and food security. Ubaka Ogbogu (University of Alberta) emphasized the need to pursue these novel therapeutic technologies guided by small “r” regulation, which focuses on proportional policies rather than outright moratoriums. Ogbogu also suggested the need for the community to plan synthetic biology ventures and outreach wisely, focusing on open communication and stewardship on behalf of those who cannot advocate concerns for themselves, as well as the importance of sharing technology and expertise with developing regions where some of the genetic resources have originated.

Synbio and Industrial Biotechnology Panel

The SynBio and Industrial Biotechnology panel saw discussion of the role of synthetic biology in manufacturing commercial products. Krishna Mahadevan (University of Toronto) discussed his group's ongoing work engineering bioprocess pipelines from end-to-end, pointing out Canada’s strength in raw materials. Pratish Gawand gave examples of how his company Ardra Bio is harnessing synthetic biology for the manufacturing of natural products for the cosmetic industry.

Sandy Marshall of Bioindustrial Innovation Canada warned that the petrochemical industry has a big head start on biology-based manufacturing with respect to bulk consumer ingredients and that it is very hard to convert biomass into bulk products at a competitive scale. Marshall suggested that high-value, more complex speciality products are a promising niche for synthetic biology-based approaches to add value.

“The petro-chemical industry has a 160 year headstart on you.”

Sandy Marshal, Executive Director of Bioindustrial Innovation Canada (BIC)

Cannabis Panel

The Cannabis panel featured discussion of the potential role of synthetic biology in Canada’s emerging cannabis industry. Hyansynth CEO Kevin Chen discussed the need for a scale up in production of therapeutic cannabinoids in order to meet growing demand, highlighting the potential role of pathway engineering via synthetic biology. Hyasynth is also currently seeking to fill positions for CFO and Head of Research. Jess Leber of Ginkgo Bioworks discussed their collaboration with Canadian company Cronos Group for the production of cannabinoids, harnessing Ginkgo’s expertise in strain engineering.

Leber pointed out that while Canadian marijuana growers may have an advantage in the short term due to differences in regulation, in the long run therapeutic and recreational production will likely rely on fermentation. Engineered strains can be used for production anywhere and can be tuned for a range of production goals. The general consensus of the panel pointed to a strong role for pathway engineering in cannabinoid production in the near future.

Agriculture Panel

The agriculture panel discusses recent advances in gene editing. From left to right: Ian Affleck (CropLife Canada), Emily Marden (UBC), Michael Lohuis (Semex), Clara Alarcon (Corteva Agriscience). (Photo by Benjamin Scott)

The agricultural panel focused on the regulatory and social challenges faced by introducing genetically engineered organisms into food production. Clara Alarcon, Director of Molecular Engineering at Corteva Agriscience, noted regulatory obstacles, like decisions by European courts to group editing technologies like CRISPR in the same category as other GMO’s, are a major barrier to making use of new technologies. Alarcon pointed out that while CRISPR can precisely modify a single target, mutagenesis which introduces many more genetic alterations,  is treated with much less scrutiny. Inconsistent and restrictive regulation are especially problematic at a time when climate change may threaten food security, and tools will be needed to adapt crops to variable growing conditions. Michael Lohuis, VP Genetics R&D at Semex, also indicated that fear among consumers is an issue the industry has still not effectively dealt with. This fear has created an environment where regulators and also competitors are each waiting for their counterparts to make the next move. There is a fear of ‘tarnishing the reputation of [something like] milk… nature's perfect food’, he said.

Several panel participants noted the difficulty in changing public perception, especially as the value of improved farming practices are often lost on people living in urban areas, far from the farm. Small companies with limited PR budgets have a difficult time changing public opinion. Lohuis noted Semex has focused on transparency as well as engineering traits that consumers see the clear social benefit of, such as animal welfare, not just what's best for the company's bottom line.

Emily Marden, of the Faculty of Law at UBC, noted that, in contrast to the previously discussed regulation, laws governing the ownership and benefit sharing for digital sequence information, which may be sourced from organisms in the developing world, is still lacking. She noted the ethical concerns going forward, as international regulation has not clarified exactly what responsibility genetic engineers using sequence information may owe to the originating regions from which they are taken. Marden suggested this benefit sharing does not necessarily need to be monetary, and could be provided through educational exchange or through job creation. She warned that it may be better for the industry to proactively address these issues before regulation makes them mandatory, as this establishes the positive uses of the technology and may convince the public of their value.

Read more in Part 2!

Amy Chen - February 10, 2019

Evening reception at SynBio Beta. The ground floor of the conference hall was filled with people. It was a great night of mingling with other Synthetic Biology enthusiasts.

SynBioBeta is a synthetic biology conference that brings together business entrepreneurs and scientists from around the world. In 2018 it was held from Oct 1st -Oct 3rd at the Mission Bay Conference Center, San Francisco. I had the pleasure of attending this conference and it was a phenomenal experience!

The first day started off with a keynote panel about the revolution in materials and a panel on how we can educate, incubate, and accelerate the next generation of synthetic biologists who will be fueling the bioeconomy. These discussions led to the SynBioBeta Awards in which leaders in public engagement and synthetic biology were recognized for their spirit, passion, and impact within the community. Dr. Christina Agapakis from Ginkgo Bioworks was recognized for her excellence in public engagement. Recognized for their excellence in leadership in Synthetic Biology were Bryan Johnson and Jeffrey Klunzinger, the co-founders of the OS Fund, a venture that invests startups that are working on breakthrough discoveries in genomics, synthetic biology, artificial intelligence, precision automation, and new materials development. Dr. Richard Kitney and Dr. Paul Fremont from SynbiCITE, UK’s national Innovation and Knowledge Centre that promotes the adoption and use of synthetic biology by industry. It was extremely inspiring to learn about these leaders who are trailblazing the way for the advancement of Synthetic Biology.

My favourite part of the night was the fireside chat featuring Steve Wozniak and George Church. This was an epic meeting of two giants of technology who were both powerhouses behind innovation that has created so much impact in the world. It was very interesting to see how two people who were different in terms of beliefs, background, and experience came together to find common ground for discussion and connect through discovering similarities.

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Fireside chat: DIY bio: The home brew computer club featuring with Mr. Steve Wozniak, Technology Entrepreneur and Dr. George Church, Harvard and MIT

The second and third day were filled with numerous keynote fireside chats, panel discussions, breakout sessions, and training workshops. Some of the highlights from those two days included a keynote fireside chat called “Neuroscience & Synthetic Biology: the Neobiological Revolution”. This workshop was particularly interesting because it presented rising synthetic biology technologies that can potentially treat neurological diseases and even enhance cognitive abilities.

During the breakout sessions, I really enjoyed the session on emerging women leaders in synthetic biology. I was elated to see a gender-balanced audience in the room who were interested in addressing the persisting problem of under-representation of women in science and engineering careers. The panelists explored questions such as how do we identify/create/amplify/become champions to encourage more women to pursue leadership within Synthetic Biology and STEM, in general?

The lightning talks by companies like Zbiotics, DNA Script, Dupont, Siolta Therapeutics, Indie Bio, and Novozymes offered a panoramic overview of the cutting-edge landscape for synthetic biology. There were many more interesting sessions throughout the second and third day. I enjoyed all of these sessions as they led me to think about issues that I have never considered and open my eyes to the breadth of synthetic biology research happening in the world.

After the three-day conference, I was able to reflect on this fantastic experience. As an undergraduate student, I have attended many academic conferences and symposiums. However, this past October was my first time attending a conference like SynBioBeta. This conference was a unique and unforgettable experience as it widened my scope of the impact and potential of synthetic biology. This event was different from academic conferences because research results and data were not the only focus of the conference. Instead of the usual poster and oral presentations, the conference was organized in a way that facilitated knowledge translation in a different sense than just research. The conference presented advances within the industry in addition to interesting research findings within academia. The conference consisted of discussions and fireside chats, which provided interesting insights into the future projection for the industry, education, and social impacts. The engaging environment inspired scientists, entrepreneurs, academics, investors, policymakers, and pioneers to use synthetic biology to build a better future. Walking into the conference, I was a bit anxious because I had no idea what to expect. However, after the conference, I walked away feeling inspired and with a renewed sense of purpose.

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There were three main takeaways for me after attending SynBioBeta.

Firstly, I was blown away by the wide range of topics presented at the conference and learned so much within the few days I was at SynBioBeta. The talks covered various intriguing topics such as Bio Meets Tech, industrial revolution 2.0, the bioeconomy culture, biopharma and health, energy and environment, and food and agriculture. The exposure to numerous diverse synthetic biology ventures within a wide range of sectors illustrated the revolutionary advances happening within the synthetic biology industry. As a past iGEM participant, it was extremely motivational to see how people have transformed their research and proof-of-concept projects into successful companies that are solving real-world problems in the world today. Not only is synthetic biology changing the field of healthcare and pharmaceuticals, but it is also making significant contributions for food, biomaterials and consumer goods. There were even out-of-this-world applications of synthetic biology that are looking into engineering biology for bio-fabrication in extraterrestrial conditions.

“I Love GMOs” display from Ginkgo Bioworks. Currently, there is still much skepticism and stigma around synthetic biology. However, I hope that through the continuous efforts of our synthetic biology community that we can openly say that we love GMOs! I think that this movement started by Ginkgo is truly inspirational and is a great trailblazer for making synthetic biology more understandable and approachable to everyone.

Secondly, the conference pushed me to be comfortable with feeling uncomfortable. The experience challenged me to make genuine and meaningful connections with other conference attendees by stepping out of my comfort zone. As one of the few undergraduate students who attended the conference, I felt a bit out of place at first. However, after talking to a few people who were now decades ahead into their careers, I realized that they started off very much in the same place I did. I was very excited to hear about their experiences and learn from their insights. Although it may seem intimidating to approach people at first, I found that people were generally very inviting and eager to share their experiences with you. For example, there were many company booths at the conference. Going around from booth to booth, I asked the representatives about their experience working in this industry and how they got to where they are today. These conversations showed me that even as undergraduate students, we have the knowledge to apply for internships within these companies. Many companies eagerly hire undergraduate students as interns and support them in their integration into various project teams. Therefore, if you are a student attendee at SynBioBeta, I would encourage you to be uncomfortable with being outside your comfort zone and to approach people who are working in sectors you are unfamiliar with.

Thirdly, this conference has allowed me to see the bigger picture for the future of synthetic biology. Oftentimes, as undergraduate students, we see synthetic biology through an academic lens. If we are doing a summer research project, many of us are focused on the scientific techniques and are less often concerned with social trends that will impact our research. However, the many panels that addressed the impact of trends in science investment, science literacy, consumer preference, biosecurity, and bio-strategies companies shed light on the importance of these factors in propelling a field.

The impact that these factors can have are not limited to the industry but are relevant to academics as well. For example, how do we teach science literacy to investors to increase their confidence in their investment? How does consumer preference affect the success of synthetic biology companies? How is biosecurity changing and what are the effects of these legislative changes? What constitutes a successful bio-strategy for companies? Realization of the impacts of these concerns has provided me with a holistic evaluation of the gap that needs to be filled in order for synthetic biology to progress. Having seen so many people who were enthusiastic about synthetic biology at SynBioBeta, I am very excited to see the amazing new advances to come at next year’s conference!

Special thanks to John Cumbers for inviting me to attend and present my iGEM Project “Astroplastic: From Colon to Colony” as part of the focus breakout session: Space applications of synthetic biology! This was a truly incredible experience!

Brendan Grue - January 7, 2019

Juliet pleaded: “What’s in a name? That which we call a rose by any other word would smell as sweet”, when referring to the irrelevance of Romeo’s rival family name of Montague in William Shakespeare’s famous play. Perhaps this draws analogy to the possible arbitrariness of naming the fields of synthetic biology as well as biomedical engineering. Would synthetic biology still hold similar associated sociological and scientific cogitations if called artificial or manufactured biology?

Like myself, you may have heard the classic physico-centric phrase from your high school physics teacher that all biology is chemistry, and all chemistry is physics. In a way, this may be true, but why then are these broad fields defined separately? Why aren’t all science courses listed under the department of physics or math? Why is it important to have a clear definition of these fields in the first place? Is synthetic biology simply just the next buzzword to induce new excitement in the already existing field of biomedical engineering?

Image credit: Brendan Grue

Biomedical engineering (BME) and synthetic biology are in some ways very similar, but also distinct fields. This relationship makes defining and separating the two quite difficult. As interdisciplinary fields, multiple definitions may apply to each. If we are to ask Wikipedia, BME is defined as: “-the application of engineering principles and design concepts to medicine and biology for healthcare purposes”. While synthetic biology is defined as: “an interdisciplinary branch of biology and engineering – [combining many] disciplines to build artificial biological systems for research, engineering and medical applications”.

Perhaps these fields are not completely mutually exclusive as some may think. Were these fields separated and labelled in an attempt to seem revolutionary towards funding agencies? From these definitions it is unclear whether these two fields are even separate, or rather just subdisciplines of one another. Some believe synthetic biology is sometimes wrongfully accused as being simply genetic engineering in disguise (not to trivialize the later), when it may not be engineering at all, instead a modification or rearrangement of existing biological systems. In genetic engineering, it is thought that the function of the transferred gene is still that of what occurs in nature, think human insulin production in bacteria, whereas synthetic biology creates end products with original or novel functions.

Through defining synthetic biology as a technological field apart from biochemistry and molecular biology and particularly systems biology, we change the way we perceive and treat this area of biology as a society from a natural understanding perspective to a goods, means, and ends framework. This perception may peak the interest in the public and those responsible for the funding of new areas of research, since synthetic biology is more interested in the application of biology to create useful systems capable of fulfilling needs, or wants, in a changing society. In addition to funding and resource allocation, defining a new area of science as distinct from existing areas may contribute further towards proper intellectual knowledge transfer in addition to multi-sector translation.

Coming back to the relationship between synthetic biology and BME, to the layperson, they may seem to be analogous terms. To the respective research communities however, their borders are more clear. Traditionally dominated by molecular biologists, synthetic biology aims largely to construct biological systems that do not exist in nature, utilizing genetic manipulation. Biomedical engineers on the other hand are thought of as engineers first, biologists second, usually possessing native tongue in the maths and physics as opposed to cellular biology and medicine. BME is largely focused upon providing inorganic solutions to healthcare needs, while synthetic biology approaches these healthcare problems, as well as problems from various other sectors, in an organic way often through the use of engineered biomolecules or living cells. In terms of applications, the engineers are thought to have an end commercial product in mind whereas this may not be the goal of the synthetic biologist, who often use synthetic biology as a tool to better understand natural systems.

A bridge between synthetic biology and BME, along with other related fields for that matter, is required to allow those working on individual components of a larger project to take the other parts for granted, otherwise known as decoupling. In this way, a single area or research group isn’t limited to its own technical expertise when deciding what it can create. Instead, those involved in the design of future synthetic biological systems are not bound to what they are themselves experts in, rather higher-level systems can be created through the application of many different experts each bringing forward single components, referred to by some as abstraction.

This ideology may however be somewhat simplistic and inherently ignorant of true biological systems, stemming from its inorganic mechanical framework and underappreciation for complex biological interactions, context dependence of parts, and responses to the environment. It may be neat to think of designed biological systems or organisms in a modular way, but final, often unpredicted, interactions between implemented parts can foil expected design outcomes, requiring ongoing redesign.

It is difficult to draw the line on what should and should not be included in both the fields of BME and synthetic biology. It may seem that their definition as a construct may be bureaucratic in nature. However, as was mentioned previously, there is utility in seeking distinct definitions for these subdisciplines, particularly regarding regulatory classification in relation to ethics, safety, security, funding, and intellectual property management. Examples of these issues relating to regulatory classification may come from the differences between classifying medical devices vs. engineered cells/biomolecules regarding health treatments, as well as the laws surrounding the patenting of medical devices compared to engineered genetic information and living organisms.

Even though there may be some utility in keeping BME and synthetic biology as separate fields, melting of their borders should be facilitated when speaking towards future educational programs and technological innovation and collaboration. Synthetic biology may just be the next natural extension of science, mirroring that of which was done with chemistry in the 19th century to form the field of synthetic chemistry and chemical engineering which contributed to early drug synthesis and the production of consumer goods. Synthetic biology may be a product of our heightened knowledge of analytic biology, like the earlier analytic to synthetic shift in chemistry. As was seen with the explosion of synthetic chemistry, the resultant economic and social impact of synthetic biology is not to be undersold. The impact of synthetic biology, and its combination with biomedical engineering techniques and knowledge, translates far beyond the health field, reaching energy, environment, agricultural, and even computing and data management sectors.

Samir Hamadache - December 25, 2018

The second day of the EUSynBioS Symposium this past October was jam-packed with presentations from senior scientists and students from all over, including Canada. Here, I summarize some of the sessions I attended. (read about Day 1 here)

SynBio Society Consortium: an international commitment to collaboration

With the international expansion of synthetic biology research, there is an opportunity for synthetic biology societies to learn from and collaborate with one another. Over lunch on the second day, we discussed some first steps for launching an international SynBio Society Consortium and potential opportunities for collaboration. Following the consortium, we produced a joint statement to assert a commitment to collaboration:

SynBioS - towards stronger international connections in synthetic biology

Accompanying the establishment of synthetic biology as a discipline, the past five years have seen many local, national, and supranational synthetic biology groups founded around the globe. United in the aims of promoting synthetic biology research as well as professional and policy development, the associations can benefit substantially from forging and maintaining strong horizontal connections.

On October 23rd, representatives from six national and supranational synthetic biology associations - EUSynBioS (Europe), SynBio UK (United Kingdom), GASB (Germany), SynBio  Australasia (Oceania), SynBio Canada (Canada), and EBRC SPA (United States of America) came together at the 2018 EUSynBioS Symposium Toulouse to set the foundation for a new international collaborative effort, the SynBioS Consortium. The representatives introduced their history, activities, and future plans through short presentations and discussed various topics of mutual interest, such as funding, social media, and science policy.

Concluding the workshop, the representatives confirmed their interest in continuing discussions as part of the future SynBioS Consortium, which will include regular online meetings focused on exchanging advice, coordinating initiatives, and reviewing progress.

We are looking forward to advancing synthetic biology together and encourage other national synthetic biology associations to join our endeavour.

~ EUSynBioS, SynBio UK, GASB, SynBio Australasia, SynBio Canada, EBRC SPA

 Standards in synbio, a new carbon-source for E. coli, and virtual organisms

Dr. Manuel Porcar (University of Valencia, Spain) kicked things off Tuesday morning with an overview of the opportunities and challenges surrounding standardization in synthetic biology. While universal synbio “parts” would be ideal to make designing gene circuits easier, Dr. Porcar highlighted that living systems are so diverse—even within the same species—that standardized synbio parts may not turn out to be as convenient as we’d like. In fact, most parts used by iGEM teams are new to the competition’s registry. Dr. Porcar pointed out that, so long as evolution is in the picture, standardizing parts for use in natural environments is futile, since the parts will naturally change over time. On the other hand, he suggests that parts could be standardized for specific chassis (host organisms) used in the lab for particular functions. For example, D. radiodurans is the go-to microbe for work involving strong radiation. He also discussed BioRoboost, a new project funded by the EU with 27 partners from Europe, North America, and Asia, aimed at finding an international consensus on defining biological standards.

Rational design and directed evolution are two techniques that synthetic biologists use to generate new biological systems: the former involves modifying or recombining biological parts from nature, and the latter involves randomly mutating genes and selecting for desired traits. From Génomique Métabolique in France, Dr. Volker Doring presented work directing the evolution of E. coli strains to produce amino acids from formic acid. Formic acid is a single-carbon compound that can be made from CO2, and so this is a valuable opportunity for biofuels and environmental remediation. In the same issue of ACS Synthetic Biology, Dr. Doring’s team also published a rational design approach to obtain the same outcome, showing that new carbon-uptake systems can be produced using both directed evolution and rational design.

Rationally designing metabolic pathways is a daunting task that Toulouse-based start-up company iMEAN is making easier using virtual organisms. To close the morning session, Dr. Lucas Marmiesse, Co-Founder and CTO, presented their company, which specializes in in-silico models analysis. Using their extensive database of gene-regulatory and metabolic networks, they create millions of “virtual organisms” that can produce a client’s desired metabolic product. Using an artificial intelligence algorithm, they identify the best design to recommend for experimental validation. iMEAN aims to simplify the design phase of large-scale projects for synthetic biology companies and researchers.

great talk by Fabien Duveau linking gene expression noise to fitness in yeast GAPDH #eusynbios18 / #biosynsys pic.twitter.com/opVRfzbHJ6

— Max Mundt (@maxmundt1) October 23, 2018

Noisy genes, metabolic engineering, and building a bioeconomy

When a gene is expressed into a protein by a cell, there are several steps that depend on random events taking place, like the right proteins finding the start of the gene on a DNA molecule. These random events result in fluctuations in the rate of the protein being produced, and this variation is known as gene expression noise.

Dr. Fabien Duveau, at Université de Paris Diderot in France, has been studying the effect of expression noise on the evolutionary fitness of cells sharing the same environments. Dr. Duveau’s research team has developed a library of yeast strains with unique mutations to the promoter of the TDH3 gene, a gene that is known to affect fitness depending on its noise level. The different mutations result in different levels of noise in the TDH3 gene, as well as different average levels of expression. Then, they compared the growth rates of these different strains. They found that when the average expression level was close to optimal for survival fitness, more noise resulted in slower growth; but when the average expression is far from the optimum, noisier expression was advantageous. In other words, when the expression of an important gene like TDH3 is much higher or lower than needed, more noise means that more cells will express the gene at levels closer to optimal, helping them grow faster.

@maxmundt1 on gene expression noise in yeast #eusynbios18 #biosynsys pic.twitter.com/ZCQiNXIT7U

— Stefano Donati (@BioSteDonati) October 23, 2018

Dr. Max Mundt, at the Max Planck Institute for Terrestrial Microbiology in Germany, is also studying gene expression noise and has developed an effective tool for precisely tuning the noise and average expression level of a gene. Being able to control expression noise is important in order to study its role in natural biology or to reduce uncertainty in synthetic systems. Their system works by allowing the experimenter to control two steps in gene expression: transcription of the mRNA intermediate, and its degradation. His team then tested this system on the mating pathway of yeast, where he was able to finely tune the noise of SST2, a key regulator of the mating behaviour.

Dr. Lorie Hamelin presented on the opportunities and challenges of a bioeconomy-based future.

Gene expression noise is not the only thing synthetic biologists want control over. Dr. Olivier Borkowski and his team at Microbiologie de l’Alimentation au Service de la Santé Humaine in France are studying the impact that expressing foreign genes has on a cell’s physiology and how the cell responds to this burden. Being able to understand this is important for the design of predictable systems and to have greater control in engineering them. After identifying key genes that are involved in the cell’s burden response, Dr. Borkowski’s team constructed a genetic circuit that is regulated by this response itself, so that the cell only expresses synthetic genes if it doesn’t compromise its own growth. This presents a useful tool for ensuring that engineered cells maintain a healthy level of growth while expressing synthetic genes.

A few presentations in this session focused on developing microbes that can produce valuable compounds or break down harmful ones. Dr. Danai-Stella Gkotsi, at the University of St. Andrews (UK), has identified and tested new halogenases—enzymes that add halogens to molecules at specific positions. At the University of Queensland in Australia, Dr. Konstantinos Vavitsas is enhancing the potential of cyanobacteria to produce terpenoids, compounds that are of value to industries such as nutraceuticals and biofuels. He presented his team’s successful production of the antimicrobial terpenoid isopimaric acid in the leaves of a tobacco plant. Dao Ousmane presented a project by his iGEM team at Paris Saclay called MethotrExit: an E. coli based “cleaning factory” for removing the anti-cancer drug methotrexate, a harmful cytotoxic chemical found in hospital wastewater.

The last presentation of the night came from Canadian scientist Dr. Lorie Hamelin, who works at the Biological Systems and Processes Engineering Laboratory in Toulouse, where she is focused on the need for sustainable and environmentally-friend food production solutions for the world’s rapidly growing population. This summer, she was awarded President Macron’s Make Our Planet Great Again grant to lead a team on CambioSCOP, a five-year project that she proposed, aimed at building a sustainable, circular bioeceonomy in France and transition to a decarbonized economy. In her presentation, she highlighted the energy and agriculture challenges of sustaining a massive world population and the need for sustainable synthetic biology solutions that do not create novel environmental problems of their own.

We ended the night with an insightful panel discussion with Drs. Olivier Borkowski, Jean Marie François, Lorie Hamelin, and Pierre Monsan. The title of the discussion was “Towards a Circular Economy”, and the panelist touched on subjects including sustainability, ecological footprints, and academic career advice for young researchers.

It was a great pleasure to attend the EuSynBioS Symposium and to meet scientists and like-minded students from all over the world. I look forward to seeing where the SynBioS Consortium takes us in the years to come!

The last event of the Symposium was a panel discussion on establishing a circular economy based on synthetic biology. Featuring Drs. Jean Marie Francois, Lorie Hamelin, Pierre Monsan, and Olivier Borkowski

Kenza SamLali - November 21, 2018

The famous ‘iGEM from above’ picture, every year, taken slightly higher up… Photo: iGEM Foundation, Justin Knight.

The international genetically engineered machines (iGEM) competition is a worldwide (under)graduate and high school synthetic biology competition, strongly embedded in the synthetic biology culture. Since 2004, teams have been inventing biological machines with the ethos of deploying biological engineering for practical problem solving for the good. Although working on team projects is not inherent to higher education in the life sciences, iGEM proves that it should be: multi-disciplinary team members from across departments get together to solve pressing problems, with socio-ethical questions in mind that fuel their drive for scientific research. With a focus on standardisation of biological designs, and responsible innovation, iGEM has in fact shaped the development of the synthetic biology field.

This year, 13 Canadian university teams and three high school teams were accepted for the iGEM Giant Jamboree at the Hynes Convention Center in Boston. All summer long, they have sweated in their lab coats, cloning from morning till morning, in addition to working on building hardware, developing software, engaging with the public and carefully publishing all their work on their website. From October 24th to 28th, the teams have been presenting their work to fellow iGEMers and an expert judging panel, of which I had the pleasure to be part of this year. Below, a summary of their brilliant work.

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Canadian iGEM teams at the iGEM Giant Jamboree pose for the first “cGEM” photo.

UNIVERSITY TEAMS

Université de Laval Bronze Medal

The team of Université de Laval performed some powerful metabolic engineering of S. cerevisiae to produce dopamine, noradrenaline, and adrenaline that can be purified and stored. With the EpiPen crisis in mind, the team aimed for a cheaper alternative for the current chemical synthesis of adrenaline compounds. Find out more on their wiki.

McGill University Bronze Medal

The Montreal team presented work on standardized cell-cell interaction for mammalian cells. They aimed to produce a universal, modular, easy to control, and orthogonal system using synNotch membrane proteins and BiTE antibodies. Read more on their wiki.

Dalhousie Silver Medal; Award Nominations: Best Environment Project

The Eastern team tried addressing aluminium toxicity in Nova Scotia’s lakes and waters. For this, they developed a point-of-care biosensor to detect aluminium, based on the bacteria Pseudomonas florescens. Read more on their wiki.

Brock University Bronze Medal

The team at Brock University decided to take a look at the famous FLIP Recombinase system, and the possibilities for optogenetically engineering it. This is foundational work that can possibly expand the synbio toolkit! Read about it on their wiki.

Queen’s University Gold Medal; Award Nominations: Best Diagnostics Project

The Queens team devoted their summer on building biosensors for the detection of glucocorticoid hormones (specifically cortisol) using both a FRET system and a system that uses intein splicing. In addition to their lab work, they have built a portable diagnostics device that can detect hormones in babies saliva. Check out their work here.

University of Toronto Silver Medal

For this years iGEM competition, the Toronto team proposed a new separation technique for bioremediation processes: the use of floating E.coli! The team engineered E.coli to produce inducible gas vesicle proteins (GvPs), in such quantity that the E.coli would float, which would be super useful in water treatment! Find out more here.

University of Lethbridge Gold Medal

The Lethbridge team decided to work with VINCEnT, a novel system for delivery of biological cargo, using protein nanocompartments (PNCs). They build several types of PCNs for the iGEM community, and developed an interesting risk assessment rubric for the use of these virus-derived systems. Find out more about this great project on their wiki.

University of Waterloo Silver Medal

The Waterloo team aimed to make co-culturing of bacteria easier, by engineering an E.coli optogenetic switch that can dynamically control E. coli growth. They engineered it in such a way that different wavelengths of light can regulate the production of MetE, an enzyme essential for bacterial growth. Read more about their project on their wiki.

University of Guelph

Ever had to deal with nasty beer brewing equipment? Calcium oxalate is a byproduct of brewing that causes your cleaning to be a really annoying task. The Guelph team looked into engineering E. coli and S. cerevisiae with Formyl-Coenzyme A Transferase (FRC) and Oxalyl-Coenzyme A Decarboxylase (OXC) so that it can uptake sodium oxalate and metabolize it. Read more here.

University of Calgary Gold Medal; Award Nominations: Best Software

The Calgary team looked at improving the current gene editing toolkit and developed a new method to insert larger constructs using CRISPR. They did this using a newly-combined system of FLP recombinases, CRISPR and Chromatin Modifying Elements. Really decent foundational work. The team was also nominated for best software, for their software SARA, an easy to use web app that can screen though past iGEM software projects. Great job! Read more on their wiki.

University of Alberta’s iGEM team nervously listening to a judge’s question. Photo: iGEM Foundation, Justin Knight

University of Alberta Gold Medal; Awarded the Best food and Nutrition project; Award Nominations: Best Integrated Human Practices

Western honeybees are threatened by Nosema ceranae, a fungal parasite. And, the only fungicide against this infection, has been discontinued. This is why the University of Alberta team decided to engineer E.coli to overproduce porphyrin, which can damage the spores of Nosema. The team has performed very well overall (project, wiki, human practices) and earned an award in ‘Best food and nutrition project’. In addition to that, their extensive work with farmers, beekeepers, and other stakeholders, earned them a nomination for ‘Best integrated human practices’. Some impressive work you should definitely check out here.

University of British Columbia Bronze Medal

The British Columbian team decided to optimise pathways in E.coli for production of Naringenin and Kaempferol, compounds often needed for cancer drugs. They developed a co-culture system that can increase the production yield of both compounds in one shot! Amazing! Read more about their work on the team’s wiki.

McMaster University Bronze Medal

The team of McMaster University tried to find a way to study neurodegenerative diseases in E.coli systems. They expressed human amyloid beta protein variants in E. coli as a system for studying the molecular basis of aggregation of these proteins, that are the cause of diseases like Alzheimer's. Find out more on their wiki.

HIGH SCHOOL TEAMS

OLS Canmore Finalist: Chairman’s Award

How can we solve the plastic problem? Reducing plastic use is one, increasing recycling efficiency is something else… The Canmore team decided to bio-tag plastics for more efficient sorting, thereby reducing the amount of global plastic ending up in landfills and oceans. For their overall project achievement, and their efforts in making the field of synthetic biology more accessible, the team has won the Chairman’s Award. This is an award for teams that show true iGEM spirit throughout their work. Read more about their project on their wiki.

Notre Dame Collegiate - High River Silver Medal

The NDC high school team took on the dirty task of breaking down fatbergs! The team designed an E.coli strain that breaks down triglycerides, by producing esterases. Quite the challenging task for a high school team! Read about their project on their wiki!

Lethbridge High Silver Medal; Award Nominations: Best Model

The Lethbridge High School looked at purifying contaminated tailing ponds, and at the same time extracting useful metals during the process. For this process, they used bacteriophages and E.coli initially. Their project is very well described on their wiki, and their impressive bacteriophage modeling earned them a Model award nomination!

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Every year, the Canadian teams are showing off more impressive projects than the year before, and a lot of that has to do with support from other Canadian teams. This year, Ontario teams met up at oGEM, about which you can read in a previous blogpost. During the Giant Jamboree, Canadian teams met up again, over midnight pizza on a windy Boston autumn night, and several Canadian team members decided to shape a more formal support network, the Canadian ‘cGEM’. “cGEM is a network of iGEM members from across Canada, getting together to build iGEM at a national level.” says Dan Lipworth, iGEM Guelph member,  “It's also a place for like-minded people to get together and share ideas about synbio and Canadian issues, meet great friends and make connections!”. Since their kick-off at iGEM, cGEM is slowly building its network across the country. You can get in touch through their Facebook group or by contacting us at SynBio Canada.

In addition to these team endeavors, Canada has shown excellence in judging as well! Every year, two prizes are awarded to the Judges who have shown excellence in their judging tasks. Two Canadian colleagues, Tessa Alexanian and Patrick Wu won the won the Rookie Judge Award and Veteran Judge Award! Congrats! I would truly encourage fellow scientists, PI’s and synbio enthusiasts to apply to become a judge at the iGEM Giant Jamboree. Being a judge will not only help you get a better picture on how a good project looks like -knowledge you can take home- , it is also a great opportunity to see science education change right in front of your nose. Such a massive gathering of the brightest minds of synthetic biology and young aspiring synbiologists is unforgettable! When I entered the Judging room, I was stunned, realizing many fellow judges are research idols I’ve been drafting (not sending) emails to for years, and I was frantically unsure what I was doing in that room. I did’t function. My brain went: Too cool. Too impressive. Too creative. Too amazing. But then you sit down and start doing your work, and realize that George Church is there for the same reasons as you, that Ginkgo Bioworks organizes their first annual Ginkgo Ferment meeting at the Giant Jamboree for the same reason as you are there. It’s the future of synthetic biology all gathered in one location!

And with such strong performance at this year iGEM, and Canada’s growing synthetic biology network, I’m looking forward to next year’s competition!

Samir Hamadache - November 9, 2018

The European Association of Synthetic Biology Students and Postdocs (EUSynBioS) held their third annual Symposium in Toulouse, France on October 22nd and 23rd. The event, which has previously been held in London, UK and Madrid, Spain, coincided with BioSynSys 2018, the 4th Conference of the French Research Group on Synthetic Biology, and the two meetings were combined.

EUSynBioS invited SynBio Canada, as well as other national & continental synthetic biology associations, to attend the event and introduce our organizations to each other. I had the privilege of attending on behalf of SynBio Canada, thanks in part to an experiential opportunity grant from Western University. This is the first of a series of posts about my experience. Unfortunately, I was unable to attend all the sessions, so I will only be summarizing presentations that I attended.

Cell-free biosensors, artificial tissues, and plug-and-play signal receptors

Peter Voyvodic at the Centre de Biochimie Structurale (Montpellier, France) is using metabolic pathways to expand the space of detectable compounds in cell-free biosensors. He has achieved stronger signals and shorter response times than in vivo systems. pic.twitter.com/2WYV9t3xPn

— SynBio Canada (@SynBioCanada) October 22, 2018

I arrived from Paris in time to hear Dr. Peter Voyvodic (Centre de Biochimie Structurale, Montpellier, France) speak about using metabolic pathways in cell-free biosensing systems to expand the range of detectable chemicals. Whereas biosensors commonly involve cells expressing chemical-detection genes, Dr. Voyvodic uses cell extracts including DNA constructs designed to sense the presence of chemicals in a solution without any cells. As a proof-of-concept, his team developed systems to sense hippuric acid and cocaine. These compounds are not easy to detect directly, so the team added genes encoding enzymes that convert either molecule into benzoic acid which is more easily detectable. In their system, the benzoic acid activates the expression of a green fluorescent protein. They found that their cells produced stronger signals in shorter times when compared with living biosensors while avoiding the maintenance requirements and constraints of a cell-based system.

Dr. Aurore Dupin demonstrating that signaling and differentiation can be engineered into an arrangement of droplets.

We then heard from Dr. Aurore Dupin, who is using bottom-up synthetic biology to assemble artificial multi-cellular systems at the Technische Universitat Munchen (Munich, Germany). In her lab, compartments made of water droplets containing E. coli cell extract and synthetic gene circuits, are fused together to simulate a multi-cellular tissue. The compartments are separated by membranes with selective pores that allow the diffusion of a fluorescent molecule between the “cells”. Using this system and a variety of gene circuits, Dr. Dupin and her team assembled artificial tissues with spatiotemporal regulation of signaling. This allows for individual compartments within the tissue to “sense” their position relative to one another, similar to the function of maternal effect genes in embryogenesis.

Dr. Jerome Bonnet presented work from his post-doc Hungju Chang and their team at the Centre de Biochimie Structurale (Montpellier, France) where they are developing a modular platform for bacterial signal receptors. The engineering of signal receptors responsive to a wide range of signals is vital for applications including environmental remediation and cell-based therapies. By pairing CadC, a membrane-bound transcription factor from E. coli, with the single-domain antibody VHH from llamas, they built a receptor that binds to caffeine and activates gene expression in response. Single-domain antibodies like VH­­Hs are ideal for their stability and combinatorial libraries, allowing for easy swapping of the ligand-binding domain to detect molecules other than caffeine. The amino acids that hold the two domains together (the “linker”) plays an important role in determining the signal response level, however, it is difficult to identify relationships between linker structure and function. So, the team developed a mutational strategy to build a library of synthetic linkers such that receptor activity can be finely-tuned by choosing the right linker sequence.

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SynBio Canada’s counterparts and breakout discussions

Today we had a very productive #synbio discussions with the national representatives from all over the world, thanks @SynBioCanada @SynBioAusAsia @EngBioRC @SynBioUK @gasb_synbio @EUSynBioS for attending #eusynbios18 pic.twitter.com/JC0gukbOta

— Huseyin Tas (@mrhuseyintas) October 22, 2018

The synbio associations then separated from the rest of the symposium for a special session to introduce ourselves to one another and learn about each other’s work. We received presentations from Dr. Christian Boehm (Chair, EUSynBioS), Matt Tarnowski (President, SynBio UK), Dr. Max Mundt (Vice Head, German Association for Synthetic Biology), and Dr. Konstantinos Vavitsas (Communications Officer, SynBio Australasia). I then presented on behalf of SynBio Canada, after which we were joined by Cassandra Barrett (President, Engineering Biology Research Consortium: Student and Post-Doc Association, USA). This session was a great opportunity to establish the foundations of an international consortium, namely the SynBioS Consortium, by discovering our shared visions & challenges and starting a dialogue on collaboration and community building.

In the evening, we had two sets of three parallel breakout sessions, covering “Science Communication”, “Standards in Synthetic Biology”, and the “Opportunities and Challenges of Building an Academic Career on Synbio”. I first attended the Standards in Synthetic Biology session, which was led by Dr. Konstantinos Vavitsas. He facilitated an open discussion with participants expressing perspectives on areas in synbio where standardization may be beneficial and/or detrimental. Some recurring themes were brought up, such as standardizing measurement methodologies and the communication of experimental results. I expressed my own interest in how standardization fits in the context of educational curricula in synthetic biology, seeing as my university is in the early stages of developing undergraduate and graduate programs. At the end of the discussion, Dr. Vavitsas provided a sign-up sheet so that interested participants could continue the conversation after the symposium.

For the second breakout session, I attended Dr. Pablo Ivan Nikel’s session on academic careers in synthetic biology. After presenting briefly about his own career trajectory in metabolic engineering, he opened the floor for questions and group discussion. Predictably, many questions centered on the choice between paths in academia versus industry and other alternatives, as well as the possibilities of combining or switching between such paths. Dr. Nikel emphasized the importance of finding a niche area of interest and skills where a synthetic biologist can set themselves apart and increase their opportunities for success.

At night, the EUSynBioS Symposium attendees took the metro together to a fine restaurant named L’Ô Zen in the heart of Toulouse for dinner and networking.

I had great conversations with young researchers about the communication of #synbio at yesterdays breakout @EUSynBioS. Thanks to all participants and the organisation :)! #eusynbios18 #scicomm #syntheticbiology pic.twitter.com/IyB645XBPh

— Nadine Bongaerts-Duportet (@nadinebongaerts) October 23, 2018

impressive growth of @SynBioCanada in a very short time! #eusynbios2018 pic.twitter.com/ZdbqdGRxzu

— GASB SynBio (@gasb_synbio) October 22, 2018

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Fatima Sheikh & Samir Hamadache - October 26, 2018

Members of the McMaster, Toronto, Queens, Western, Guelph, Ottawa, Waterloo and Brock iGEM teams, who attended the Ontario “oGEM” conference at McMaster University, July 28 2018.

The McMaster iGEM team has experienced drastic growth since its beginnings. Going into our fourth year, we are currently a team of almost 40 members making up 5 different subteams: Wet Lab, Dry Lab, Human Practices, Business Development, and Community Outreach. Our previous projects have included the use of light to control recombinant protein production (2015), the use of quorum sensing with genetically engineered lactic acid bacteria as a novel therapy for gastrointestinal tract cancers (2016), and developing a plate- based biosensor for E. coli through the use of fluorescent DNAzymes in an effort to tackle antibiotic-resistant bacteria - a growing public health issue both in Canada and overseas (2017). This year, in addition to taking on a new research project, we had the pleasure of hosting the annual oGEM conference!

The Ontario Genetically Engineered Machine Network (oGEM) Conference is an annual event that brings iGEM teams from across Ontario together to discuss their research projects, initiate collaborations and discuss both the successes and challenges of synthetic biology research. This year, in addition to having Dr. Benjamin Scott, SynBio Canada President and iGEM alumnus come to speak to us about his research in synthetic biology, we introduced a student synbio roundtable discussion session.

The conversation, initially proposed by Ontario Genomics’ Manager of Strategic Planning, Dr. Jordan Thomson, was designed to address the discussion paper resulting from the inaugural 2018 Canada SynBio conference and workshops. However, what started as a conversation on synthetic biology research quickly shifted to the biggest challenges facing the synbio community in Canada, the lack of synbio education at the undergrad level, and funding & resources for iGEM teams.

(1) the field of synthetic biology lacks a clear definition that distinguishes it from existing disciplines like molecular biology

(2) there’s an absence of undergraduate-level courses and programs, and being an interdisciplinary field, this means students are lacking necessary knowledge and tools

(3) undergraduate programs in synthetic biology would help foster much needed interdisciplinary communication

Several members of the SynBio Canada Steering Committee also participated in the oGEM conference (left to right): Dr. Benjamin Scott (President), Fatima Sheikh (McMaster University) & Samir Hamdache (Western University)

Despite some of the highlighted challenges, the conversation remained optimistic on the potential for synthetic biology in Canada and the role students will play in disseminating synthetic biology to a wider audience.

Over the next month as we prepare for the upcoming iGEM jamboree we will be putting together an oGEM recap video in collaboration with SynBio Canada and the Ontario iGEM teams. This video will shed light on the challenges associated with this emerging field and the action that is needed to address these challenges, from a students perspective.

Each year the oGEM conference grows and gives all participants an opportunity to learn about one another's work, the new initiatives we have taken on, and to form partnerships to move synthetic biology forward. It was an absolute pleasure to host the event at McMaster and we look forward to seeing everyone at next year's conference. In the meantime stay tuned for our recap video and all the amazing work being done by students across Ontario.

SynBio Canada is committed to working with and advocating for the synthetic biology student community & iGEM teams across the country. Check out our growing list of Canadian iGEM team profiles--if your team isn’t represented here, let us know! We plan to help strengthen channels of communication among teams and support the synbio student community in advocacy efforts.

Andrew Diamond, Samir Hamadache and Laura Prochazka - September 18, 2018

Dr. Bogumil Karas (Western University) showing that many organisms can contribute to GP-Write.

The first Genome Project Write (GP-Write) Canada meeting was hosted in Montréal on August 13-14th 2018, organized by Dr. Vincent Martin (Concordia University), and Dr. Bogumil Karas (Western University). GP-Write is an international consortium of researchers with the ultimate goal of creating a synthetic human genome. GP-Write is a continuation of the Human Genome Project (HGP) which, from 1990 to 2003, produced the sequence of the complete human genome. The effort of the International Human Genome Sequencing Consortium significantly reduced the costs of DNA sequencing by developing new technologies and making it more accessible. Today, reading genomes has become an established technique. Now, we are entering an era that goes beyond reading genomes. It is about writing (or creating) them. In fact the first bacterial genome was synthesized in 2010 at the J.Craig Venter Institute and the first synthetic yeast genome (Synthetic Yeast 2.0) is currently under development.

However, writing genomes continues to be challenging, and many more hurdles must be overcome to move from bacteria and yeast to human genomes. One of the major bottlenecks is the difficulty of DNA synthesis itself, in addition to the assembly, delivery, installation, and editing of synthetic genomes.

But why do we want to synthesize human genomes at all? Creating the whole or parts of the human genome will advance our understanding of how genomic elements function as a system. Or as Richard Feynman put it, "What I cannot create, I do not understand". This will allow us to study gene interactions to model diseases and to develop new drugs. And it will largely facilitate the development of advanced gene- and cell-based therapeutics for the treatment of currently incurable diseases.

GP-write has already held two international scientific working meetings where leading Canadian scientists, including Bogumil Karas, Vincent Martin, Peter Zandstra and others, have expressed their interest becoming part of it. Thus, the objective of the GP-write Canada meeting was to determine who else in Canada is interested to build a GP-write Canadian consortium, which Canadian resources and scientific expertise can be leveraged, and which potential projects and strategies will attract funding to synthetic genomics research in Canada. The event attracted more than 70 participants from across the country, including scientists, industry leaders, and ethicists who introduced their work and discussed related questions over the course of two days.

“Biology is the most sophisticated manufacturing technology on the planet: self-repairing, self-assembling, self-replicating, renewable, resilient.”

— Dr. Kevin Madden

Day 1

The workshop started with an afternoon of inspirational talks by industrial and academic leaders in the field, covering the past, the present, and the future of genome writing.

• Dr. Andrew Hessel inspired us with a short personal and scientific story that covered the early days of DNA sequencing, the first “synthetic” bacterium, and a future world when synthesizing human genomes may become mainstream.

• Dr. Bogumil Karas proposed that synthetic biologists specialized in different host organisms tackle various stages of the synthetic genome engineering cycle including design, DNA synthesis, assembly, delivery, and editing. Bogumil gave a comprehensive technical road-map on many of the challenges that have to be overcome in these various stages. He also suggested that cell fusion could be used to deliver large chromosomes into plant cells.

• Dr. Leslie Mitchell (Boeke lab) talked about current progress and challenges of the Synthetic Yeast 2.0 project that aims to build the world’s first synthetic eukaryotic genome. She also shared her recent work in transplanting and analyzing synthetic genomic loci in mouse embryonic stem cells.

• Dr. Kevin Madden presented on Ginkgo Bioworks foundries that allow the undertaking of several projects in parallel by automating synthetic biology using advanced robotics.

• Samir Hamadache (Western University) highlighted the need of accelerator programs dedicated to synthetic genomics, so Canada can emerge as a leader in the industry.

“You don’t need to work in human cells to contribute to GP-write Canada.”

— Dr. Bogumil Karas

Day 2

The second day started with a series of talks by researchers from various Canadian universities to elaborate what research is currently in progress in Canada and how it can contribute to the GP-Write Canadian consortium.

Dr. Miodrag Grbic (Western University) brings back the importance of good quality genomic data.

• Dr. Aashiq Kachroo (Concordia University) is working on humanized yeast by swapping multiple yeast genes with their human versions for drug-screening or to assay genetic diseases.

• Dr. Sebastian Rodrigue (Université de Sherbrooke) showed that his team successfully cloned the entire genome of Mesoplasma florum into yeast and they are working on new techniques for genome assembly and transplantation into microorganisms.

• Dr. Scott McComb (National Research Council) is using CRISPR-deletion techniques to make multiple knockouts simultaneously and map pathways in human T cells. He suggested to use human T cells as chassis for developing, integrating and studying synthetic genes and genomes.

• The importance of the ethics and of good communications to the public in the GP-Write project was highlighted by Dr. Marc Saner from the University of Ottawa.

• Dr. Teodore Veres (National Research Council) is working to scale down wet lab workflows with automation and precision using lab-on-a-chip and microfluidic technologies.

• Dr. Michael Tyres (University of Montreal) talked about his work on CRISPR/Cas9 genetic screens in human cells and on engineering yeast strains that produce defined small molecules to modify the human microbiome.

• Dr. Steve Hallam’s team from the University of British Columbia is working on automated high-throughput screening platform for enzymes function discovery.

• Dr. Laura Prochazka (University of Toronto) is engineering gene circuits to manipulate the decision-making of human stem cells and proposed human pluripotent stem cells as a chassis to analyze and study the synthetic chromosome.

• A good quality genome needs good sequencing techniques as reminded by Dr. Trevor Charles (University of Waterloo). He also highlighted current gene editing work in agriculture and greenhouse technology and how GP-write can contribute in these fields.

• Dr. Charles Boone (University of Toronto) created a genetic interaction map of the yeast genome and functionally annotated each gene. He highlighted that automation of the process of creating multi-genic knockouts is required to accelerate the establishment of such a genetic interaction maps.

• Dr. Miodrag Grbic (Western University) is studying the genomics of spider mites and he is proposing that the small genome of this eukaryote could be synthesized as a proof of concept before going directly to the human chromosome.

Like Dr. Sebastian Rodrigue (Université de Sherbrooke) and his team, Canadian researchers have multiple expertise that can be integrated to a Canadian consortium.

The afternoon of Day 2 was broken into two focused breakout sessions. In small working groups, we first discussed Canada’s unique opportunities and challenges with respect to GP-Write. For the second breakout session, groups were organized based on their expertise and/or interest in various taxa of host organisms. Participants discussed ways in which Canadian expertise with different hosts can contribute to a unified GP-Write strategy.

The notes generated by the discussions were compiled by George Brook from the Agricola Group and Vincent Martin, who will produce a report on the conference’s outcomes. This document will then be used to lobby for funding agencies.

We have learned a lot of exciting work and ideas throughout this workshop and had fruitful discussions with an enthusiastic and diverse group of people, showcasing that Canada could become an important actor in the GP-Write worldwide consortium.

Benjamin Scott - August 31, 2018

Hosted by: Dr. Jordan Thomson, Ontario Genomics

Participants: Dr. Rebecca Shapiro (University of Guelph), Dr. Trevor Charles (University of Waterloo), Dr. Brendan Hussey (University of Toronto), Dr. Kathleen Hill (Western University), Dr. Mark Daley (Western University)

The panel discussion was well attended, highlighting the significant interest in synbio at Western University. Image courtesy of Western University Science.

As a follow-up to the first Canada Synthetic Biology conference in March 2018, Ontario Genomics hosted a panel discussion at the Western Synthetic Biology Symposium 3.0 to discuss where the field is headed in Canada. Dr. Jordan Thomson, Manager of Strategic Planning at Ontario Genomics, moderated the event. Dr. Thomson also gave an overview of the significant contributions that Ontario Genomics has made to synthetic biology, pointing to their recent white paper (pdf) that outlines strategies for fostering the field in Canada.

Questions and replies have been edited for brevity.

What in synthetic biology are you excited about, and what does the synthetic biology community need?

Dr. Kathleen Hill and Dr. Mark Daley were excited about the capabilities of synthetic biology, both in its applications and as a research tool. Discussing biology research from a computer science background, Dr. Daley stated that “synthetic biology is just going to be a part of biology…giving us the tools to reprogram life as information processing systems.”

Dr. Rebecca Shapiro was excited and impressed by the recent growth of hubs and training programs specifically focused on synbio (i.e. at Concordia and Western). She felt that researchers should better engage with the public, to explain the field and address public concerns.

Dr. Trevor Charles was very enthusiastic about iGEM, stating that “there would not have been synthetic biology at Waterloo without the Waterloo iGEM team.” (Notably, student enthusiasm and participation has been leading the charge at Western as well, leading to the recent creation of a dedicated training program.)

Dr. Brendan Hussey was excited about recent new hires at Canadian universities of researchers with a synthetic biology focus. However, he stated the need for a champion in Canada, to lead a unified vision for promoting the field (which came up during the Canada Synthetic Biology 2018 conference as well). He also questioned the significance of grassroots synbio initiatives, believing instead that government and university recognition of synbio is essential, especially to attract researchers from the US and overseas.

“There would not have been synthetic biology at Waterloo without the Waterloo iGEM team.”

— Dr. Trevor Charles

 What can we in Ontario/Canada be doing better to foster synthetic biology?

Dr. Jordan Thomson (Ontario Genomics) moderated the panel on the “Current and Future State of Synthetic Biology in Canada”. From left to right: Dr. Kathleen Hill, Dr. Mark Daley, Dr. Rebecca Shapiro, Dr. Trevor Charles, Dr. Brendan Hussey. Image courtesy of Western SynBio Symposium.

Dr. Mark Daley expressed his frustrations as an interdisciplinary researcher, posing the rhetorical question, “what NSERC subject code do I pick?” when it comes to submitting grants. He noted that the NSF in the US is working to change how they review grants, to make it more accommodating to interdisciplinary research proposals.

Dr. Trevor Charles stated that the lack of government support is hampering the growth of Canadian synbio start-ups. He stated that a program like the US SBIR grants should be implemented, which fosters small business research and development. The Government of Canada appears to have recognized this need, having recently launched similarly styled “Innovative Solutions Canada” grants. However, as of August 2018, public challenges utilizing synthetic biology have not been issued.

Dr. Rebecca Shapiro stated that since it’s difficult to compete with the US, which has a larger per capita research budget, Canada should focus its synbio efforts on specific niches. However, deciding on these niches poses its own problems, which Dr. Hussey believed could be helped by having a synbio “champion” to focus Canadian efforts. Dr. Kathleen Hill also stated her desire to hear from the larger research community, to determine what these niches are.

“I need you, but I don’t understand you.”

— comment from Ontario farmer in the audience

The panel was concluded by opening it up to questions from the audience, summarized below:

To best communicate the importance of synthetic biology, one conference participant stated the need to focus on commercialization, and not just having an academic approach to research.

Another conference participant, a farmer from southwestern Ontario, had many suggestions and remarks for the panel. Expressing his frustration with anti-GMO rhetoric and lack of clear science communication, he stated that “I need you, but I don’t understand you.” He also strongly believed that unless synbio researchers can learn to engage with the public, “we are not going to have you around unless you stand up for synthetic biology.” Turning to the audience, he asked “what language can you use to explain synthetic biology to people?”

Benjamin Scott - August 31, 2018

Poster presentations at the Western Synthetic Biology Symposium 3.0. Image courtesy of Dr. Kathleen Hill.

The third annual Western Synthetic Biology Symposium was the largest yet, with over 150 attendees, 30 posters, and oral presentations throughout the day. Although focused on synbio research happening in southwestern Ontario, there were speakers from both industry and academia from across Ontario and Quebec. Dr. Cintia Coelho traveled the furthest, all the way from the University of Braslia, to present her work on using integrases for genome engineering, and highlighting the truly international scope of synbio research.

The day was kicked off by industry talks, where representatives from Ontario companies Specific Biologics, Designer Microbes Inc., and Ardra Bio discussed their exciting technology and spoke enthusiastically about their collaborations with Canadian universities. The US company SGI-DNA also showcased their new BioXp 3200 “DNA printer”, which automatically constructs custom DNA fragments as large as 1.8kb. Western University recently acquired one of these machines, which costs up to $65K/year to maintain. But, Dr. Karas (Western University/Designer Microbes Inc.) was quick to point out that by splitting costs between labs, access to this machine is relatively affordable. In addition, synthesizing DNA directly enables the design of complex DNA libraries, saving time and money versus traditional molecular biology techniques.

Next, Dr. Jordan Thomson from Ontario Genomics hosted a panel discussion on the “Present and Future State of SynBio in Canada”. This discussion built on the Canada Synthetic Biology 2018 conference in March, also hosted by Ontario Genomics. Featuring a panel of professors and postdocs from four different Ontario universities, the wide-ranging panel discussion is summarized in a companion article (read about it here).

Dr. Rebecca Shapiro (University of Guelph) gave the keynote presentation, and presented her exciting work on developing functional genomic tools to study pathogenic fungi. Shockingly, the number of deaths per year due to fungal infections is equivalent to HIV/AIDS, but the development of new anti-fungal compounds has lagged in recent years. She described her use of CRISPR gene drives to stably engineer these otherwise difficult to study fungal strains, which is a resourceful new tool for understanding these pathogens.

Dr. Rebecca Shapiro (University of Guelph) giving the WSB 3.0 keynote presentation, on her work to identify drug targets in pathogenic fungi using synthetic biology tools. Image courtesy of Western SynBio Symposium.

The day was capped with presentations from graduate and undergraduate students, representing the newest generation of synbio researchers in Canada. Excitingly, Western University is launching its own synthetic biology training program at the undergraduate and graduate levels, the first of its kind in Ontario. Members of the student-led Western Synthetic Biology Research Group (WSBR) discussed their efforts to promote and launch this program, which gained momentum due to strong student interest. The WSBR is now leading an undergraduate research program, focused on experiential learning in synbio. This example of student leadership paired with support from professors is an inspiration for other synbio programs across the country! (read the SynBio Canada article about the WSBR here)

Dr. David Edgell gave concluding remarks, expressing his excitement about the growth of synbio in Ontario. He also called for ideas on launching a “grand challenge”, which could be solved through collaborative efforts by researchers in southwestern Ontario. This enthusiasm perfectly summarized the conference, where the growth of local synbio research programs is leading to exciting new opportunities for southwestern Ontario and beyond.

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Conference organized by: Drs. David Edgell, Bogumil Karas, Kathleen Hill. Conference website, list of sponsors

For more photos, see the Western Synthetic Biology Symposium twitter account.

Nathan Braniff - July 13, 2018

Dr. Trevor Charles is a professor at the University of Waterloo. He is also the co-founder and CSO of Metagenom Bio Inc., and director of the Waterloo Centre for Microbial Research.

This month we discuss synbio, regulation, and science advocacy with Professor Trevor Charles. Dr. Charles has been a professor in the department of biology at the University of Waterloo for 20 years and has been a strong advocate for synthetic biology research, both at Waterloo and in Canada. He is also the co-founder and CSO of Metagenom Bio Inc., which develops and commercializes microbiome solutions in environment and agriculture. He received his PhD in molecular biology under Prof. Turlough Finan at McMaster, studying the genetics of Rhizobium meliloti. His current research continues to focus on the study Rhizobium species and interactions with their eukaryotic hosts. His group has also developed novel functional metagenomics methods and in 2015 he received an Ontario Genomics SPARK award to engineer biological approaches for the recycling of waste methane into bioplastics. He recently became the director of the Waterloo Centre for Microbial Research (WCMR), a new multidisciplinary initiative using microbiology to benefit the economy, environment and human health. He is also very active with science advocacy and outreach on twitter and can be found @trevorcharles.

How would you define synthetic biology, in one or two sentences, for a lay reader?

Definition is one of the hardest things about synbio. It is one of those things that you either intuitively understand, or don't get it at all. I think that is one of the problems in getting the message out to outsiders. I very much like the idea of applying engineering principles to biology, with a strong implementation of technology such as gene synthesis, gene editing, and genome engineering.

Could you explain some of your recent research related to synthetic biology?

I am a bacterial geneticist, so I like to think that I have been working in synthetic biology since before the term was coined. The great thing about bacteria is that you can manipulate the genome at many different levels. For example, my grad work involved making large genome deletions with defined endpoints. We have also developed ways to stably integrate DNA segments into defined regions of bacterial genomes, and to produce bioplastics with novel properties, in some cases using DNA isolated from metagenomic libraries. Some new work involves engineering methanotrophs to produce bioproducts using methane as carbon source. This is interesting because methane is a potent greenhouse gas, and is also one of the least expensive carbon sources, being produced in wastewater treatment plants, landfill sites, biogas plants, as well as being present in abundant natural gas reserves.  

Do you think that the synthetic biology research output from Canada has kept pace with other countries or is Canada falling behind? What needs to change? Are there any advantages that Canada offers?

Definitely not. We have very little synthetic biology research in academia, and hardly any commercial activity. There is lots of interest, for example through iGEM, but it hasn't really caught on at other levels. I don't know what advantages Canada could offer. We certainly don't have any presence on the international stage. A bold move would be for a funding agency to allocate funds towards unfettered synbio research, with no requirement for co-funding for industry partners. As it stands, there is very little capacity for synbio in this country, because it hasn't been supported by research funds. As an example, one might have expected the Genome Canada Disruptive Innovation in Genomics competition to be dominated by synthetic biology. This was not the case. Canada has lots of potential, but limited developed capacity.   

Do you feel that the Canadian regulators and funding agencies strike the right balance between supporting progress in synbio vs limiting the risks involved in a new field? If not, where can Canada improve and are there other countries with funding/regulatory models we might look to for examples?

The focus should be on funding scientific research rather than studies on risk. We will never develop a strong synbio community by focusing on risk. And focusing on risk will give Canada a reputation of a precautionary jurisdiction to be avoided for synbio investment. Not a good idea. Just look at what has happened with Europe and agricultural biotech. The stifling regulatory climate there strangles biotech development.  

You have an active twitter presence where you regularly post about scientific topics. In your opinion how important is outreach and public education to the success of synthetic biology and the potential GMO products it creates? Do scientists communicate enough?

Outreach is incredibly important. But there will be limited success in trying to educate the public about the safety of GMOs and synthetic biology. What really needs to be done is to get people to be enthusiastic about science in general, and to understand how science is carried out. What are scientists excited about, and why? What technical developments arise from scientific advances? What is the role of serendipity in science? Application of science to challenges in agriculture, health and environment, and how it makes our lives better. Canada has an unenviable record of harbouring fierce critics of biotech, such as CBAN and ETC. In some cases there are close links between these anti-science groups and some academics in Canadian universities. A campaign by CBAN was instrumental in killing the Enviropig project, based at University of Guelph. Ironically, the Enviropig was developed to reduce environmental impact of raising swine, and many the fiercest opponents considered themselves to be environmentalists. Arctic Apple and Aquadvantage Salmon were developed in Canada, and should be celebrated as Canadian innovations, but how often do we hear about them in a positive context? It is remarkable that they were able to make it through the regulatory process. Hopefully, the regulatory system will evolve along with the application of new genome editing technology, and new traits will make it to market in an efficient manner.

Are you optimistic about synthetic biology in the future or do you feel it has been over-hyped? Is there any specific industry where you think synthetic biology research is currently making a real commercial impact?

Yes and no to hype. But I think the general public is surprisingly unaware of synthetic biology. The industry that I think has the greatest potential to benefit in the short term is agriculture, both plant and animal.

In the long term, what do you see as the biggest obstacle to the goals of synthetic biology? Do you think synthetic biology/bioengineering will ever resemble other more mature engineering disciplines (ie mechanical, civil, electrical)?

Biology is complex. The biggest challenge is how to deal with and overcome this complexity. Hopefully there will be opportunities for Canadian scientists to address these challenges.

Do you have any suggestions as to the future steps SynBio Canada can take to promote synbio research in this country?

I think raising public awareness about synthetic biology and its potential applications is important. Op-eds, newspaper and magazine articles, radio and TV interviews, and social media are all activities that could contribute to this. Perhaps SynBio Canada might be able to coordinate some of this.

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More information about Dr. Charles's research can be found at his website.

More information on Metagenom Bio Inc. can be found here.   

For information about the WCMR and ongoing initiatives at the University of Waterloo, see here.

Taylor Sheahan - June 20, 2018

Chris Isaac at the Meeting of States Parties to the Biological Weapons Convention (BWC) in Geneva, Switzerland.

In 2017, the University of Lethbridge Collegiate iGEM team aimed to lower barriers to synthetic biology to the public, by developing a modular and safe cell-free platform. Cell-free approaches to biological engineering provide a promising alternative to cell-based systems. This is due to their reduced complexity and potential for bio-contamination, as wells as novel engineering capabilities, such as the ability to incorporate non-canonical amino acids and toleration of toxic compounds. Due to the inherent safety of cell-free platforms, the team envisioned such a system would provide a powerful tool as an educational platform, which could be used to teach students the basics of synthetic biology. Additionally, the cell-free platform would be accessible to the public, enabling "DIY" enthusiasts and biotechnology start-ups. 

Although the potential for cell-free platforms is high, it is necessary to address the potential misuse of cell-free systems and develop a strategy to mitigate the threat of suspicious users. This is where Chris Isaac, a member of the U of L iGEM team, comes in. Isaac identified that the flexibility of cell-free systems makes them highly amenable to genetic recoding, where canonical relationships between codons and anticodons are not necessarily consistent. Thus, there is the potential for dangerous users to “encrypt” sequences that, when synthesized using a novel genetic code, will produce a harmful compound. To address this threat, Isaac aimed to develop software that would identify recoded sequences to ensure that they will not be synthesized. At the 2017 iGEM Giant Jamboree, Isaac and the team were acknowledged for their ability to identify biosecurity risks associated with cell-free systems, as well as for their initiative taken to develop mitigation strategies. 

Building on the momentum from the Giant iGEM Jamboree, Isaac was selected along with four other students to travel to the UN campus as an iGEM delegate. In the winter of 2017, the delegates attended the intersessional Meeting of the States Parties to the Biological Weapons Convention (BWC) in Geneva, Switzerland. 

“At the convention, we were able to attend the plenary sessions and listen to statements made by the parties” says Isaac. “While these statements appeared to be largely formality, they were in fact glimpses into long-standing issues, brief remarks on current events, and calls to action for the continued support of the BWC.” 

The delegates had the opportunity to discuss biosecurity and synthetic biology with representatives from around the globe, creating an open dialogue between young scientists and regulatory officials. 

“The experience provided a great look into how governments prevent and control biological threats, and was also a good introduction to the non-governmental agencies who are working on these problems.”

Continuing his work towards addressing biosecurity threats associated with synthetic biology, Isaac received the Emerging Leaders in Biosecurity Fellowship at the Johns Hopkins Center for Health Security, which fosters the development of the next generation of leaders in biosecurity. Isaac is one of 28 individuals selected, and is also the youngest member of the 2018 class. 

iGEM delegates, including Chris Isaac (second from Left), at the BWC in Geneva, Switzerland.

“I was thrilled to have been selected as a fellow and have since travelled to Washington, DC for the first fellowship meeting. We had the opportunity to meet with staff of the National Security Council on the White House campus and discussed national-level priorities for biosecurity, challenges, and the direction that biosecurity programs are headed.”

Currently, Isaac is a Biochemistry Master’s student at the University of Lethbridge in the lab of Dr. Athan Zovoilis. In addition to graduate studies and the fellowship program, he is participating in his 7th year of iGEM, as well as continuing to develop his biosecurity software suite. 

“With both of these experiences combined, my most important takeaway is two-fold. First, there are great people working on issues of biosecurity from all sides, they come from all walks of life, and work at all levels of administration; international, national, state, provincial, academic, and non-governmental. Secondly, it reaffirms my belief that scientists need to be more involved with government, and communicate outside of academic or industrial silos. We should be seriously considering dual-use implications for even basic research that might enable other unrelated technologies to be used improperly”.

Taylor would like to thank Chris Isaac for sharing his experience.

BENJAMIN SCOTT - MAY 13, 2018

As part of SynBio Canada’s continuing efforts to grow the synthetic biology community, we’ve begun reaching out to researchers both in Canada and abroad. The reception has been incredibly welcoming, which has left us with an abundance of researchers to connect with. This article is the first in a series of Quick Chats, meant to highlight the diverse range of research interests and ideas within the community.

Dr. César de la Fuente Nunez, a Postdoctoral Associate and Ramon Areces Foundation Fellow at MIT, working with Prof. Timothy K. Lu.

Dr. César de la Fuente Nunez is a Spanish-Canadian synthetic biologist, where he received undergraduate training at the University of León, then moved to Canada to complete a PhD at the University of British Columbia. César is currently a Postdoctoral Associate and Ramon Areces Foundation Fellow working with Prof. Timothy K. Lu at MIT. He has a passion for both science and soccer, and with another MIT colleague he’s the coach and plays on the MIT FC.

César is interested in fostering a robust synthetic biology community, in Canada and abroad, so we sat down with him to discuss his ideas about the field.

Where does your interest in synthetic biology stem from? What are your working on right now?

I believe synthetic biology can be used to build truly innovative new technologies to solve real world problems. In my research, working at the intersection between synthetic biology and computational biology, I engineer biological systems (such as tiny proteins) to make novel potential medicines. One of the global health challenges I have targeted through my research is that of antibiotic resistance. With my collaborators around the world, I have provided an array of solutions to combat drug-resistant infections.

Your research background is incredibly diverse, from materials science, to genome editing, to microbiology. Where does synthetic biology fit into all of this?

 Synthetic biology converges all these fields. I would argue this is the power of this emerging field, that it bridges different disciplines to create new technological tools and advances. Getting people from all these fields to interact, brainstorm and share ideas has been transformative and has enabled synbio to evolve into what it is today.

In what industries or applications do you foresee synthetic biology having the greatest impact in the next 10 years? What are you excited about?

Dr. de la Fuente Nunez recently published his work to create a yeast-based system for the rapid production of anti-microbial peptides. Link to paper.

Image: Ella Marushchenko, provided by Dr. de la Fuente Nunez.

The medical field. But I also foresee practical applications in bioremediation, energy and catalysis. At the moment, I am personally most excited and most personally invested in trying to translate synthetic biology-based applications into the clinic.

What programs or initiatives have worked well to support synthetic biology research?

I think the support from universities and governments is key here. In addition, I believe the field has benefited from conferences dedicated entirely to synbio, and to journals such as ACS Synthetic Biology from the American Chemical Society, which focus exclusively on this field.

MIT has a strong synthetic biology background, with a diversity of expertise. Is there something unique about MIT that has fostered this?

MIT was one of the first strong supporters of this new field, and this is clearly reflected in the institution. We have the MIT Synthetic Biology Center (where I work) that houses some of the most brilliant minds in the field, including some of its founding fathers. The interdisciplinary nature and lack of boundaries of MIT as a whole has definitely boosted the development of a strong synbio community.

Are there specific resources you would find useful for strengthening synthetic biology in Canada? What would make Canada more attractive for synthetic biology?

I believe combining efforts among groups interested in synbio, for example through regular meetings/conferences, etc. will certainly strengthen the synbio community in Canada. Having a genome foundry would be a great resource and strengthening ties with industry would also de highly desirable. Federal funding would also need to back up this emerging field. In the US, not only NIH, but also DARPA and DTRA among others have been instrumental in funding and supporting synbio efforts and initiatives.

How can the interdisciplinary nature of synthetic biology be better leveraged, and avoid isolating researchers into many individual departments? Have you faced any challenges communicating synthetic biology either to the public or to other academics?

Science is becoming increasingly interdisciplinary and collaborative, and I think the field of synbio has benefited from this. Most tools and scientific advances developed within the field of synthetic biology have a “real world” application. Therefore, I would argue that it is actually easier to communicate such advances to the public. Because the public can easily relate to the societal problems synbio is trying to tackle.

Synthetic biology is often characterized as a tool for conducting research, while others define it as a distinct field with a primary focus on applications outside of the lab. What’s your own definition of synthetic biology?

I see synthetic biology as a discipline of disciplines. A converging field that borrows concepts from classically distant or unrelated fields such as engineering, computer science and biology.

SAMIR HAMADACHE - APRIL 13, 2018

Nucleases: “Bigger, better, stronger”

Dr. David Edgell is the Acting Chair of the Department of Biochemistry at Schulich School of Medicine and Dentistry (Western University).

While the scientific community and now much of the public is excited about CRISPR/Cas9, some synthetic biologists like Western University’s Dr. David Edgell are working away at creating the next generation of DNA-editing tools. As Associate Professor and now Acting Chair of Western’s Biochemistry Department, Edgell is engineering nucleases “to make them bigger, better, stronger…more accurate, and having a more defined function.”

Edgell’s research began with asking basic questions about mobile genetic elements—DNA fragments capable of moving from one genomic position to another. They do this by using enzymes called homing endonucleases, which are nucleases that introduce double-stranded DNA breaks at precise sequences. “It quickly became clear that we could adapt this protein for genome-editing applications,” Dr. Edgell says. “So, over the past eight years, that’s what my lab has been really moving towards.”

Specifically, the Edgell Lab focusses on developing genome-editing nucleases for applications in various model systems. His latest creation? A fusion of Cas9 with I-TevI homing endonuclease, producing a dual nuclease termed TevCas9. The easy-to-use dual nuclease offers greater target-site specificity than Cas9 on its own and circumvents one of the biggest challenges of Cas9: regeneration of the target site.

“A lot of scientists realize the limitations of Cas9”

Despite its proven utility, The Cas9 nuclease confers a disadvantage upon CRISPR-based gene-editing. When Cas9 cuts DNA, a straight cut through the two strands of DNA leaves blunt ends. This promotes a DNA repair pathway called non-homologous end-joining (NHEJ), which “will simply take those blunt ends and jam them together, regenerating the Cas9 target site,” Edgell explains. However, since this repair pathway is imperfect, bases are occasionally lost or added in the process. Eventually the target sequence is disrupted, preventing further cleavage, and effectively knocking out the targeted gene.

It’s a messy process. The length and nature of base mutations at the target site depends on the rather unpredictable cycle of target site cleavage and regeneration. Dr. Edgell’s TevCas9 dual-nuclease, consistently deletes fragments of defined length. The fragment deleted is between the cut sites of each nuclease. After NHEJ repairs the break, the target site is lost, and the futile cycle is avoided altogether.

This allows for more reliable and predictable gene knock-outs. Another crucial gene-editing task is to perform gene knock-ins by inserting new DNA fragments at targeted locations. For this, a different DNA repair pathway is needed.

In order to insert a new DNA sequence at a DNA break, repair involving homologous recombination (HR) is required. As the blunt ends produced by Cas9 promote NHEJ, HR is promoted by a staggered cut that leaves overhangs instead. This is a challenge that many scientists are currently working to overcome. “The idea is to trick Cas9 into making ends that are not blunt ends, or to add another domain onto Cas9 to promote homologous recombination in some way,” says Edgell. “It’s kind of the next big holy grail in genome engineering.”

It’s not the only challenge Cas9 currently faces. Studies in recent months have discovered a pre-existing immune response to the Cas9 protein in adult humans. Although this presents an obstacle in gene therapy efforts, Edgell is optimistic that it’s a challenge that can be circumvented because Cas9 could be engineered to make it unrecognizable to the immune system. This would be done by modifying the epitope (3-dimensional surface structure) that antibodies are recognizing.

Advancing synthetic biology at Western University

In addition to engineering more useful nucleases, Dr. Edgell is collaborating with other scientists to apply nucleases like TevCas9 for synthetic biology applications.

One project with fellow biochemistry professors Dr. Greg Gloor and Dr. Bogumil Karas is aimed at using TevCas9 as a “molecular warhead” for high-precision control of microbiome populations. In effect, harmful bacteria can be targeted without damaging helpful bacterial populations. In addition to human health applications, this approach could be extended assist in industrial food production (such as yogurt probiotics) and environmental cleanups.

In another collaboration with Dr. Karas, Edgell is working to increase the utility of the algae P. tricornutum. This species of algae is a popular candidate for biofuel production, but Karas and Edgell think it is also very promising for the biosynthesis of other high-value products.

Outside of the lab, Edgell is working with other Faculty and Administrators to bring synthetic biology to the forefront at Western University. “I think there’s a lot of interest in synthetic biology at Western. [We] are trying to develop an umbrella structure to promote synthetic biology research.” Along with Dr. Kathleen Hill, Dr. Karas, and others, Edgell has applied for a large internal grant to formalize ongoing efforts such as an undergraduate synthetic biology module, a collaborative graduate program, and the annual summer Synthetic Biology Symposium.

“This is a really exciting time to be involved in synthetic biology. The promise of synthetic biology is massive.”

-Samir would like to acknowledge Rachel Boyd’s influential help editing this article.

BENJAMIN SCOTT - MARCH 20, 2018

The second day of Canada SynBio 2018 was a smaller, closed-doors meeting to specifically discuss how to support and grow synthetic biology (synbio) in Canada. Members of the SynBio Canada Steering Committee (Laura and Ben) were fortunate to attend, to offer insight from early career researchers and students who are striving for dedicated support of synbio in Canada.

Funding Synthetic Biology Panel. From left to right: Bettina Hamelin, President and CEO, Ontario Genomics (Moderator); Marc LePage, President and CEO, Genome Canada; Paul Lasko, Director Institute of Genetics, CIHR; Ted Hewitt, President, SSHRC; Mario Pinto, President, NSERC. Image courtesy of Dr. Leslie Mitchell, NYU, Sc2.0 project.

Several times during the second day of the conference, the desire to identify and build the synthetic biology community in Canada was expressed. This is precisely the goal of SynBio Canada, and we’re excited to provide a platform for the research community to connect and collaborate!

Here we summarize the second day of enthusiastic discussion and debate surrounding the future of synthetic biology in Canada, to bring the suggestions and concerns of the participants to a larger audience. There were many fantastic ideas, which will also be further elaborated on by Ontario Genomics in a future white paper. Thank you to Ontario Genomics and ISED for hosting an engaging conference.

Highlights are presented in bold text for a faster read.

Richard Johnson, CEO of Global Helix, Director of iGEM Foundation and the Engineering Biology Research Consortium

Richard discussed the trends and efforts that have led to dedicated support for synbio in the US. Rather than the unique case of the UK, where support was government led, support for synbio in the US has come from a variety of sources. He organized his presentation into “synbio headlines”, with the key drivers for synbio support in the US.

• Biology has been made easier to engineer through the standardization of genetic “parts”. This has been successful for E. coli and yeast, but not yet for mammalian cells.
• Biotechnology contributes ~2.5% to the total US economy (approx. $500 M per year). Synbio is a convergence of biology and engineering, which DARPA has recognized as a major pillar of production and advanced manufacturing. This has lead to dedicated funding from several US federal sources, particularly the Department of Energy, DARPA, and NIST.
• Synbio is leading to new business models, and government can act as a key funder + de-risker through financial support for these new business ideas. Private investment will follow, and it’s growing rapidly.
• Synbio is advancing so fast that it threatens to overwhelm current regulations. Safety must be addressed from the outset of any project.

Vincent Martin, Co-Director of the Centre for Applied Synthetic Biology, and Professor at Concordia University

Vincent has been a strong and vocal proponent for synthetic biology in Canada. During his talk, he discussed his personal efforts at Concordia University to build their synbio capacity, and listed his ideas to strengthen the field at a national level.

• He opened with a frank discussion regarding the history of synbio support in Canada, or the lack there-of. Meetings in 2009, 2012, and 2014 have led to numerous suggestions, but little action at a national level.
• He also discussed the difficulty in maintaining support for an iGEM team. He discussed the increasing costs for participation in the iGEM competition and that it relies too heavily on volunteers for supervision and teaching. He called for institutional support for the iGEM concept, or perhaps a Canadian equivalent, which directly provides for undergraduate training in synthetic biology. He also expressed the need to provide a path for trainees to move from iGEM teams into a graduate project.
• Canadian universities must become better at developing biological engineering programs. He explained that students are desperately calling for this, but universities are slow to react.
• The solution that Vincent devised for Concordia, was to create the Centre for Applied Synthetic Biology (CASB), to gather expertise from various departments into the same institute. This was made possible thanks to an ambitious new university president, who called for proposals for clusters of research, to help a smaller university like Concordia become a leader in specific fields.
• Vincent also discussed his frustration with current funding panels in Canada, as they don’t recognize synbio as a distinct field. He also stated that NSERC simply doesn’t have a mechanism to fund an interdisciplinary synbio network (see later sections for the response from funding agencies).
• One of the components of CASB is a genome foundry, which includes automated equipment to rapidly assemble large pieces of customized DNA. He stated that the foundry is meant to act as a proof-of-concept in Canada, and they’re looking for collaborators to use it.
• He also expressed the need to better support the entrepreneurial talent of synbio researchers. Again, Concordia University is being very proactive with this, with the launch of their D3 innovation hub, and dedicated lab space which is soon to be built.

Specifically regarding the future white paper, which will summarize the ideas from the conference, Vincent offered this advice:

1. Need a champion in government or an NGO, to ensure the proposals are acted upon. They should be impartial, not directly benefit from any proposed funding, and work to bring the community together. Mona Nemer, the Chief Science Advisor of Canada, seemed like a potential “champion”. (In the later breakout discussion groups, Vincent Martin was also discussed as a potential “champion”.)
2. Who in government will a proposal/white paper be handed to? It’s not clear who at the federal level can act on these proposals. So, despite a wealth of ideas, the receptor of the white paper still needs to be addressed.

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Following these presentations were a series of breakout sessions, to discuss key challenges and opportunities for synthetic biology in Canada.

Highly Qualified Personnel, Students, Skills, and iGEM

Challenges:

• Limited funding for multi-discipline research and “long shots”/big risk big reward projects.
• A need for a common forum for the community (which is what SynBio Canada wants to contribute to).

Opportunities:

• “Transdisciplines” where ethics, safety, social science informs the science being conducted. Jennifer Kuzma elaborates on this in her own article, stating that “I’m continually impressed by the Canadian ethos of diversity and inclusion---why should technological research and development be different? Canada has a prime opportunity to lead in the design and execution of responsible innovation for synthetic biology.”
• Connections between institutes, where the experiential-based learning of colleges and polytechnics could be paired with university programs, to provide direct experience in biotechnology.

Research and Access to Technology and Facilities

Challenges:

• Lack of core facilities. Canada’s expansive geography limits access, and there’s an uncertainty of what already exists.
• Grant review panels are not amenable to interdisciplinary grants.

Opportunities:

• Greater transparency of core facilities, such as the equipment available and how much it costs to use.
• A registry of existing resources.

Commercialization and Translation

Challenges:

• Lack of funding, need a SBIR style of program (which has been successful in the US).
• Lack of lab space, and available mentors.
• Regulatory barriers. Inconsistent regulations, and it’s difficult to know which government agency should be involved.

Opportunities:

• Called on funding for the pre-commercialization stage, with a direct ask from Genome Canada for support.
• Short term focus: natural resources and agriculture, using waste as chemical feedstock.
• Long term focus: healthcare, such as CAR-T therapy and personalized medicine.
• “Limitation is only imagination” when it comes to applications of synthetic biology.

The final three breakout sessions (Ethics, Regulation and Public Trust; Leveraging Canada’s Strengths; Building on International Initiatives) are collectively summarized below.

Challenges:

• Difficult to know who/where synbio researchers are in Canada (SynBio Canada aims to help with this!)
• Who are the key international partners?
• Need to be very strategic in how synbio-themed grants are currently funded.

Opportunities/Actions:

• A coordinated effort between different sectors to define synthetic biology and collaborate
• Focus on ethics and regulatory steps early, as they compliment research (not a hurdle)
• Work to frame synthetic biology more in a positive light, discussing the benefits rather than the technology
• Use inclusiveness/”niceness” of Canadian culture as a strength to recruit research talent
•  Focus on big projects/moon shots/grand challenges as a coordinated effort to strengthen synbio
• Create a community or National Centre of Excellence to specifically focus on synbio
• Create a culture to think/collaborate globally
• Identify research areas/applications that are internationally competitive
• Opportunity to send trainees between genome foundries/synbio facilities across Canada

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Granting Agency Panel

The day was capped with a panel discussion involving representatives from all major funding agencies (Genome Canada, NSERC, CIHR, SSHRC). The enthusiasm of the day was somewhat tempered by the reality requesting dedicated synbio funding from these agencies. Interestingly, none of the funding agency representatives acknowledged synthetic biology as a distinct field, and were hesitant to brand research this way. Mario Pinto, the president of NSERC, suggested that when writing grants researchers instead focus on the applications of their research.

Researchers in the audience expressed their frustration with this strategy, as it has led to little perceived support for synthetic biology in Canada. The interdisciplinary nature of the field seemed to preclude it from traditional grants which have focused on more rigid definitions of research fields.

To address this conflict, the panel brought up “challenge-based calls”, which are grants that focus more on a specific challenge in medicine/industry/society, and are open to many research strategies to address these challenges. Challenge-based calls for artificial intelligence research are apparently upcoming, so it’s possible synthetic biology could be next.

There was also discussion of the recently announced increases towards science funding in Canada, which will include new funds to encourage interdisciplinary projects. Such grants may be more amenable to synthetic biology research and applications, but it’s still too early to say.

Final Thoughts

The US and UK have become leaders in synthetic biology due to the initial dedicated government funding, followed by sustained public and private financial support. The specific strategies employed by the US and the UK to reach this point, however, are slightly different. Where the US was led by various government agencies that recognized synbio is key to industrial competitiveness, the UK was led top-down from the federal government with a specific national strategy. But, whatever the strategy is, dedicated funding specifically for synthetic biology is clearly key.

It’s now time for Canada to build on these strategies and put the excellent ideas from the Canada SynBio 2018 conference into practice.

BENJAMIN SCOTT - MARCH 19, 2018

A fun analogy from Dr. Rob Holt (University of British Columbia) comparing small molecule therapy to synthetic biology.

On March 6th and 7th 2018, the first national conference on synthetic biology in Canada was hosted in Toronto. Organized by Ontario Genomics and Innovation, Science and Economic Development Canada (ISED), the conference brought together over 275 students, professors, industry leaders, and policy makers from across the country, and from the UK and US.

The event was split into two days, with the first day focusing on synthetic biology (synbio) success stories in Canada, and comparisons to how other countries have fostered their own synbio community.

This blog post will summarize the presentations and discussions of the first day, with some additional thoughts from the SynBio Canada Steering Committee. A blog post about the second day, which focused directly on how synbio can be fostered and strengthened in Canada, will follow tomorrow. We also encourage you to read Ontario Genomic’s summary, and Dr. Shawn Lewenza’s summary on his own site.

Opening Remarks

The conference was kicked off with encouraging statements from Ihor Boszko and Marc LePage, representing Ontario Genomics and Genome Canada respectively. Mona Nemer, the recently appointed Chief Science Advisor of Canada, also stated her support via video. She explained that the interdisciplinary nature of synthetic biology is precisely the sort of science she’s excited about, and that she too has a background in DNA synthesis.

Keynote: Engineering Biology in the Era of Genomics

Replacing the usually staid nature of academic conferences, Bill Peck the CTO and Co-Founder of Twist Bioscience, was welcomed to the stage with a rousing rock intro of Smoke on the Water by Deep Purple. Bill discussed how synthetic DNA is enabling a move beyond a reliance on petrochemicals to create energy, fuel, and plastics. He also discussed Twist’s collaboration with Microsoft and the University of Washington to use DNA as data storage, which faithfully stored jazz music. He also used an interesting analogy, explaining that each human body has many orders of magnitude more information than all of the digital data hosted on Facebook.

Keynote: Building a Successful Synthetic Biology Ecosystem

The second keynote address was particularly interesting to those of us working to strengthen synbio in Canada. Stephen Chambers, the CEO of SynbiCITE in the UK, gave a detailed overview of how the field has received significant support in his country. His definition for synbio, which is one of the easiest to grasp, was that synbio “is using biology to build useful stuff.”

Stephen described how political leadership in the UK has been the driving force behind the country’s strong support for the field. Synbio was identified as one of eight technologies that the UK must invest in, to remain competitive in the 21st century. By betting on specific technologies, not applications, the UK government avoided “picking winners”, which is a common criticism of government-led investments.

“Most people aren’t interested in the technology, they’re interested in the benefits.” – Stephen Chambers, CEO of SynbiCITE

He then went on to describe the mission of SynbiCITE, which is to nucleate synbio applications in the UK. By focusing on jobs and wealth creation as a direct result of synbio investment, SynbiCITE has made a strong case for supporting synbio at a national level.

An overview of synbio entrepreneurship since the launch of SynbiCITE revealed that 37 new companies had been created and sustained, receiving £13M in grants and £234M in private investment. Importantly, SynbiCITE found that these companies were specifically concentrated nearby the synbio accelerators that had been founded, showing a direct positive impact on local economies wherever synbio is supported.

Stephen also imparted specific lessons learned:

1)      What drives science, doesn’t drive business

2)      Build on local capabilities

3)      Synbio needs both public and private investment to flourish

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Panel Summaries

There were many great discussions throughout the day, but to keep things brief, here are a few quotes from the various panels.

AI and Computation Meet Synthetic Biology

“First computing chemistry in silico…and then finding the organisms and genes which create these chemicals.” - Nathan Magarvey of McMaster University and Adapsyn Bioscience discussed his work to discover next generation therapeutics.

“What if you could google the next drug?” – Ratmir Derda, University of Alberta and 48 Hour Discovery. A fun presentation involving a water bottle, showing how an entire chemical library could be rapidly screened by genetically encoding molecules.

Reducing our Carbon Footprint with Synthetic Biology

“A 100% reduction in greenhouse gases and 67% reduction in energy costs.” - Cathy Hass from BioAmber discussed the many benefits of switching from petroleum based production to biology based production of succinic acid.

“Microbes may have already solved our problems for accessing and storing resources.” – Steve Hallam, University of British Columbia

Human Health – From Gene Editing to Stem Cells

 “A lot of work still to do understanding (cellular signaling) pathways, and then moving to building new ones.” – Peter Zandstra, University of British Columbia, discussed the current promise and challenges facing the development of new cellular therapies.

“We need to build immunotherapy capability in Canada, so we are not beholden to multinational drug companies.” – Rob Holt, University of British Columbia, showcased the exciting immunotherapy studies currently being performed in Canada, and the need for a national strategy to ensure the country has the capacity to use this breakthrough therapy.

Vincent Martin (Concordia University) identifying a big hurdle facing synthetic biology, which The Centre for Applied Synthetic Biology is working to solve with their genome foundry.

Writing Genomes

 “What are you going to build (with DNA) and why?” – Leslie Mitchell from NYU and the Sc2.0 project imparts the lessons she learned from designing custom organisms.

“Ethics is mostly about why yes to do something, not no.” – Vardit Ravitsky from Université de Montréal on the benefits of engaging early with bioethics. “Avoid sensationalist language…take the lead in debating the implications of your research.”

“We work to engineer complex phenotypes.” – Vincent Martin from Concordia University on the many applications of the genome foundry at his institution. He specifically stressed the importance to engage in the GPWrite project, and wants to host a meeting in Canada in August 2018.

VC Investor Showcase

Taking an idea beyond the lab is daunting, especially when developing a business around it. Ken Nickerson from OMERS Ventures imparted advice for scientists/entrepreneurs, stating that although it may seem that entrepreneurs are beholden to investors, it’s the investors who are desperate to find good ideas to support.

Food Biotech 2.0 and Learning from GMOs

“Need efficient, predicable, consistent regulatory frameworks (for GM crops).” – Ian Affleck, CropLife Canada

“What does it mean to scientists to innovate responsibly?” – Jennifer Kuzma, Visiting Research Chair at the University of Ottawa, poses a challenging question to the audience.

“90% of surveyed consumers had high likelihood to buy. The other 10% wanted chocolate dip, or red ones.” - Neal Carter from Okanagan Specialty Fruits discusses their Arctic Apples product, which are apples that do not brown.

SynBio Start-Ups

The final panel of the day was a showcase of the diverse synthetic biology start-ups from across the country.

Bougimil Karas, CEO of Designer Microbes discussed their work developing proprietary vectors for cloning and maintaining large DNA fragments. They’re interested in fostering year-long collaborations with academics, and are particularly interested in soil microbes.

David Lloyd, CEO of Fredsense posed the question “do you know what’s in your water?”. There’s a $22B market for chemical testing, but it usually takes days to get results. They’re working to create modified organisms that can detect contaminants within an hour.

Hans-Joachim Wieden showing off the impressive synthetic biology community at the University of Lethbridge.

Hans-Joachim (HJ) Wieden, Director of SynBridge discussed the need to “support a community of practice”. He has helped create a space for synthetic biology students, enthusiasts, and entrepreneurs to test their ideas in a real lab. SynBridge is part of a greater synthetic biology community, centered at the University of Lethbridge.

Justin Pahara, CSO of Amino Labs talked about how they’re interested in “not the what but the who of synthetic biology.” Amino Labs creates kits for after school programs and public workshops to foster a do-it-yourself style of education. Interestingly, he stated that New Brunswick has by far the most active hands-on synbio community in Canada.

Kevin Chen, CEO of Hyasynth Bio showcased their efforts to create yeast which produce therapeutic cannabinoids. Through synthetic biology, they aim to tackle the $6B blackmarket for cannabis, and address the issues of scale facing the extraction of cannabinoids.

Leo Wan, CEO of Ranomics discussed their gene library service, offering targeted mutagenesis for up to 15 kb of gene. This aims to revolutionize biologics development, and how we understand how proteins function.

Pratish Gawand, CEO of Ardra Bio showed how natural ingredients can be obtained by engineering cells to produce them, rather than extracting them from crude oil. Instead, all it takes is the right engineering cell and some sugar.

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Final Thoughts

It should be noted that these seven start-ups represent the entirety of the current synbio entrepreneur community in Canada. This is compared to the 37 companies that have been formed in the UK, thanks to dedicated financial support from the UK government. Canada clearly has a lot of catching up to do, and this conference was a step in the right direction. In many cases, this was the first time that members of the Canadian synbio community were meeting face-to-face, which is key to develop strong research and business relationships going forward.

The support voiced throughout the conference by policy makers and granting agencies was very encouraging, and SynBio Canada is excited to contribute to making a stronger synbio community. The second day of the conference, a smaller closed-doors meeting, directly focused on what Canada must do to support synthetic biology at a national level. Members of the SynBio Canada steering committee participated in these discussions, which will be summarized in a future blog post.

The SynBio Canada Steering Committee would like to thank Ontario Genomics and ISED for hosting an engaging conference! Stay tuned for our summary of Day 2.

SAMIR HAMADACHE - FEBRUARY 25, 2018

 By the students, for the students

WSBR student directors presenting their work at Western Research Forum 2017. (from left to right: Kevin Zhou, Luana Langlois, Ashmita Singh)

As the synthetic biology scene grows at Western University (London, Ontario), the Western Synthetic Biology Research Program (WSBR) is giving undergraduates the opportunity to design and create their own functional living systems.

The WSBR club was founded in 2016 by a group of first-year students aspiring to create a team for the International Genetically Engineered Machine (iGEM) competition. Today, WSBR is facilitating two independent student projects, coordinating a focussed journal club (“SynBio Talks”), introducing high school students to synthetic biology, hosting a case competition (“SynBio Hacks”), and working with Faculty to create an Honors Specialization in Synthetic Biology.

“WSBR started from a desire to see more people getting the same opportunities that we did,” said third-year honors genetics & biochemistry student, Luana Langlois, co-founder and now Co-President of WSBR. While working on their iGEM project, Luana and her peers discovered that there was a lot of interest in synthetic biology among Western students and researchers alike. As a result, they formed WSBR to give the opportunity to more undergraduates to make their own synbio idea come to life.

When WSBR first opened its doors to new members in late 2016, over 200 students applied within the span of one week. New members could meet like-minded synthetic biology enthusiasts, learn about ongoing initiatives, develop new skills, and launch their own projects.

While student leadership is at the heart of the program, WSBR is endorsed and supported by Western’s Departments of Biology and Biochemistry. Members are provided with lab space, equipment, funding, and most importantly mentorship. Graduate students and faculty members from the two departments volunteer by assisting the undergraduates with their projects, answering their questions, and teaching them new skills.

Where are they at? Just getting started!

According to its website, WSBR “[performs] scientific research in order to tackle major issues such as climate change, energy production, and personalized medicine”. This is achieved by genetically engineering algal and bacterial model organisms to carry out desired functions.

Currently, there are two teams of students working on separate projects.

One team is in charge of developing novel biological tools to enhance the rate of conjugation (DNA transfer) between algae and bacteria. Such tools would facilitate the synthesis of large artificial chromosomes and increase the versatility of eukaryotic systems. The other group is working on increasing the tolerance of algae to acidic environments. This is environmentally relevant as the acidification of oceans and lakes, largely resulting from atmospheric pollution, threatens algal communities and the stability of aquatic ecosystems.

Past projects include enhancing carbon and nitrogen metabolism in the nitrogen-fixing bacterium S. meliloti, engineering E. coli to serve as a visible indicator of pH levels, and similarly, engineering E. coli as an indicator of temperature levels.

Outside of the lab, WSBR is also involved in outreach and academic initiatives. SynBio Talks is a journal club, where anyone interested in synthetic biology can meet and discuss recent publications in the field. Representatives from WSBR also sit on a task force of Western’s Biology and Biochemistry Departments that is developing an undergraduate specialization in synthetic biology.

Stepping up to the challenge: the WSBR’s case competition and iGEM team.

SynBio Hacks is the WSBR’s case competition. Introduced in late 2017, it is aimed at bringing new students to the lab so that they, too are given the possibility to bring innovative ideas to life. While the competition is only open to Western students for its pilot year, Luana sees the potential for expansion in future years.

Participating teams of 4 will present thesis proposals to a panel of judges comprised of faculty members. In addition to designing a practical application for synthetic biology, teams will be expected to consider funding, timelines, required iGEM kit parts, and other logistic parameters. This year’s theme is “Eutrophication: the suffocating effects of climate change”.

Although WSBR was born out of an effort to create an iGEM team, Western does not currently have an official representative team. Other universities in Ontario, such as Waterloo and McMaster, have established quite successful iGEM teams. WSBR is in the process of creating a new division, “UWO iGEM”, for the purpose of representing Western in the international competition.

“I see WSBR growing into a big program, and Western becoming a centre for synthetic biology,” Luana enthused. “I want to see people interested in [synthetic biology], and applying it in their careers.”

I look forward to seeing WSBR keep growing!

Learn more about WSBR at www.uwo-wsbr.com.