By Emma Lindsay - APRIL 18TH 2024

Dr. Sébastien Rodrigue is a professor at the Université de Sherbrooke in the Department of Biology. His research focuses on microbial systems, synthetic biology, and genomics to understand microbial genomes and develop methods to modify them. He is also the Co-Founder of TATUM Bioscience, a therapeutic company that uses synthetic biology to develop immunotherapies.   

Can you tell us about yourself and your research?  

I did my BSc and PhD in the Département de Biologie at the Université de Sherbrooke. During my thesis, I was interested in understanding the full genetic program of a bacterium using Mycobacterium tuberculosis as a model. I considered cells as “living robots” that could eventually be programmed to yield better vaccines or new therapies. However, M. tuberculosis was already a complex and specialized pathogen, which directed me to search for simpler model systems that would be easier to fully grasp. This led me to start a postdoc at the Massachusetts Institute of Technology where I studied Prochlorococcus, a very abundant marine cyanobacterium with a small genome and very few transcription regulators that could potentially be hacked for biotechnological applications. Prochlorococcus was fascinating but proved to be much more difficult than I anticipated for different reasons. I developed a collaboration with Tom Knight as a side project and started working on Mesoplasma florum, which is a mycoplasma-like bacterium with an even smaller and even simpler genome of about 800kb and 685 genes. I was recruited back at the Université de Sherbrooke and decided to focus my lab on minimal genomes and synthetic genomics. Since then, my group uses M. florum but also E. coli to develop new tools and therapeutic approaches using synthetic biology. 

Why did you decide to use Mesoplasma florum as a model? What made it easier to work with?  

M. florum has one of the simplest genomes while also growing fast with a doubling of approximately 30 minutes. In contrast to other small genome mycoplasma, M. florum is an insect commensal that has no known pathogenic potential. It is also easy to get colonies on agar plates, which sounds straightforward, but for some bacteria like Prochlorococcus can be difficult. Overall, it was a fast-growing organism, with a small genome and a good potential to do interesting synthetic genomics projects.   

 What inspired you to go into synthetic biology?  

I think it was the vision that cells are machines, and that if we understand them enough, we could reprogram and engineer them for various applications. I like to say synthetic biology is like studying a putative alien technology: if we had a UFO to dismantle and play with the parts, we could potentially understand it sufficiently to rebuild a flying machine or even create new technologies.   

Your work consists of modifying the genomes of organisms; do you think the public has a good understanding of its applications?  

No, I don’t think the public knows or understands exactly what synthetic biology is about. This can raise concerns, especially in the post-COVID era. It would be important to explain the goals of synthetic biology, the potential benefits, and the intense work on biocontainment mechanisms to ensure safety. This will be particularly important if we want to build new therapies that can treat and cure patients without any additional risk of infection. I think there will be a lot of innovation in that area in the coming years.   

Where do you envision the field of synthetic biology being in the next five years?  

I think we are just starting to see the true potential of synthetic biology. Most circuits that we build right now only have a few genes. This is enough for many applications, but in my opinion, we will slowly move towards more complex circuits, and synthetic genomes that offer interesting properties such as ease of engineering, modularity, genetic insulation, and resistance to viruses. I also hope it will become much cheaper to write DNA since this remains an obstacle for many projects and that we will see more real-world applications in addition to fundamental advances. 

Your research can be applied to a wide range of applications such as medicine and the environment, where do you think your research will have the greatest impact?  

I think at first, it will be in the medical world. Biology had most of its notorious achievements in medicine, and it is probably easier for synthetic biology to reach these applications. However, I hope that we will be able to address environmental problems. We know that climate change is a major challenge and synthetic biology has potentially a lot to offer, for example with carbon dioxide sequestration. There are also a lot of opportunities in food production. Our way of producing food contributes to and will be threatened by climate change. If we had better ways to grow our food or if we could invent new food, I think that could have a major impact. But again, people will have to understand and accept genetically modified organisms. Consumers still have the last word in the end.   

You co-founded TATUM Bioscience, can you tell us about the goal of TATUM bioscience and what inspired that?  

TATUM bioscience was initially started on a microbiome editing technology that could selectively and efficiently eliminate antibiotic resistant bacteria directly in the intestinal tract. However, the company rapidly pivoted for different reasons and is now creating a new type of immunotherapy to treat various types of cancer. 

The main motivation for starting the company was to maximize the chances of societal impact of the technologies that we develop. We decided to be proactive and create our opportunities instead of simply hoping to potentially be noticed by pharmaceutical companies or VC funds. A crucial step was to submit patent applications whenever there was significant intellectual property to protect. We were also fortunate to be supported by the ACET National Bank incubator based in Sherbrooke and to raise funding with private investors. There are many programs to help create startups in Canada and this can be an interesting path for students interested in synthetic biology.   

What advice would you give to students interested in pursuing a career in synthetic biology or related fields?  

I would say that it is obviously important to master theory, laboratory techniques, and ideally bioinformatics (that’s a good tool that not enough people have) but my advice would be to cultivate creativity. Synthetic biology will reach its full potential only if we can imagine clever solutions to important problems. So, think about specific problems that you would like to solve and be creative. Then, go to your computer or to the lab and really try to change something. Another possibility that is important to consider for students is entrepreneurship. There is momentum being built in Canada for SynBio companies. Fundamental research is great, I really loved it, but another way to have an impact is to start companies and have products reach the market. I hope that many SynBio students will be interested in that possibility and that they will start companies. I have done it with a former PhD student and a colleague, others can do it too!   

Dr. Sébastien Rodrigue’s work in modifying microbial genomes highlights the potential of reprogramming living systems. Looking ahead, he strives for the expansion of complexity, affordability, and safety in the synthetic biology field. Based on his experience with TATUM Bioscience, he hopes to inspire students to do the same, fostering innovation and driving progress in the field. 

Benjamin Scott - June 12, 2023

These tips could apply to anyone looking for a non-tenure track position of any type. Many of the tips could likely be applied to tenure track job hunts too.

The difference between a CV and a resume

• A CV (curriculum vitae) describes everything you’ve done during your entire career post-high school.

  • This means every publication, every conference presentation, every award, all your teaching experience, every society/volunteer experience, and a comprehensive list of your technical abilities.

• A CV is long, often 5+ pages

  • A CV is typically only used for applications to tenure track positions, or very specific technical positions at research institutes. They are not typically requested for any other role.

  • The same CV is often used for many job applications (it is not usually tailored to the job ad).

• A resume is specific to the job ad you’re applying to. It does not cover your entire career, only the most relevant aspects to the job you’re applying to.

• A resume is short, no more than 2 pages. You may want to create a longer “master” resume, and adjust it to suit the job ad.

The key sections to a resume are typically:

• Name and contact information

• Profile: a 2-4 sentence summary about you, your key skills, and accomplishments. It’s the first thing the hiring manager will read, and will re-read before your interview. Short and punchy.

• Professional experience: summary of your employers, job titles, and how long you worked there. Under each one, list 2-4 bullet point accomplishments. Accomplishments are what you did, not how you did it. Don’t summarize technical accomplishments, unless relevant to the role you’re applying to. If you can’t think of any accomplishments, then the experience isn’t worth including. This will take up ~50% of your resume.

• Education: very short summary of the degree(s) you earned, from what school(s), and when.

• Selected publications: 2-4 publications, if relevant to the job you’re applying to. Reference format of your choice.

• Selected conferences & presentations: 2-4 conference presentations, or other presentations, if relevant to the job you’re applying to.

• Volunteer experience/hobbies: this can help show you have activities outside of work. Some hobbies can come across as unprofessional, so be careful what you list.

• Additional links: LinkedIn, Google Scholar, ORCID, GitHub, etc.

• Optional sections

  • Skills: These must be specific skills, highly relevant to the job posting. “Teamwork” and “MS Office” are not serious skills. But a specific programming language, or technical skill may be relevant to include. These skills should set you apart from other candidates. Be prepared to discuss specific ways you’ve used these skills.

  • Awards and distinctions: if particularly notable, relevant to the job, and/or something you would like to bring up in an interview.

  • Teaching experience: only if the job will involve teaching. You could instead include this under professional experience, to demonstrate you can train people.

The importance of a cover letter

• A cover letter is almost as important as your resume. It’s your chance to tell your story, and why you’re perfect for the job. It is one page and clearly includes:

• Header including your contact information

• The job title you’re applying to

• A short summary of yourself/accomplishments (similar to the profile on your resume)

• A list of specific accomplishments relevant to the position (in point form, if that’s helpful)

• Specific reasons why you’re interested in this role

• Summary paragraph, relating your accomplishments to why you’re a perfect fit for the job

• Your signature and printed name

What to focus on (in applications and interviews)

Employers want to hear about your experience, and how you work on a team. Teamwork is undervalued during grad school, but it’s a crucial component of jobs after school.

• Focus on two major things

  • Your accomplishments (what you did, who it impacted, why it mattered)

  • Your experience working on a team (size of teams, skillset of teams, your contribution)

If there are specific technical skills mentioned in the job ad, you should also highlight those. But avoid talking at length about your technical skills.

It’s much more important to highlight what you accomplished with those skills, who it impacted, why it mattered.

Job ads, and when to start looking

You do not need to meet all criteria on a job ad. If you’re excited about the opportunity, and can meet ~50% of the listed criteria, you should apply.

~18 months before you plan to start a new job, start looking at job ads at companies/institutes you want to work at. If you find a role you like, use the job ad as a template for the skills you should be developing. Grad school is the perfect time to learn new skills, and take advantage of courses/seminars.

~12 months before you plan to start a new job, start reaching out to contacts at companies/institutes you want to work at. This could be emailing, or messaging on LinkedIn. Messaging on LinkedIn often results in a reply. This is an opportunity for an “informational interview”, a chance for you to learn about the company and the roles there. Most importantly, you will now be on the company’s radar. There are often unlisted positions/roles that have not been advertised yet, so you may learn about them.

 Keep this timeline in mind when job hunting: The interview and hiring process for technical roles, particularly academic ones, can be very long. Expect 2-4 months from your initial application to the final interview. It can then still take a few more months for you to start.

References

• Create a list of 2-5 key people

• Former supervisors, bosses, colleagues, people you have trained

• Ask them before you provide their names as references

• Tell them about the job you’re applying to, and when to expect to be contacted, and what the interviewer may ask about

• Communicate communicate communicate!

Preparing for an interview

Ahead of the first interview, think of a few “S.O.A.R” stories (see here for more)

• Situation: You begin by briefly providing context using a real life situation you experienced. This is the “before” picture which illustrates what was happening “at the time” of the situation.

• Obstacles: You then articulate the issues or define the problem. This gets the interviewer’s attention regarding what it is you had to overcome.

• Action: You then explain the action you took to resolve the situation.

• Results: Share the result of your actions. Sharing the quantifiable as well as qualitative outcomes.

Write them down if it’s helpful, and practice them ahead of the interview.

When you find out who will be interviewing you, take 30 minutes to do some research about them before the interview.

The interview process

Each company/institute has a slightly different interview process. You should have a chance to meet your supervisor, team members, and other colleagues during the process.

The interview is not just about you. It’s also your chance to learn more about the company, and the people there.

Here are some questions you could ask. Obviously you won’t have a chance to ask them all, so choose the ones you feel are the most important.

Adapted from: https://www.academyoflearning.com/blog/6-types-questions-ask-job-interview/

Questions to Ask About the Job:

• What does a typical day look like?

• What are the most immediate projects that need to be addressed?

• Can you show me examples of projects I’d be working on?

• What are the skills and experiences you’re looking for in an ideal candidate?

• What attributes does someone need to have in order to be really successful in this position?

• What types of skills is the team missing that you’re looking to fill with a new hire?

• What are the biggest challenges that someone in this position would face?

• What sort of budget would I be working with?

• Is this a new role that has been created?

• How does this role connect with the larger work being done at the company? 

Questions to Ask About Training and Professional Development:

• How will I be trained? What does the onboarding process look like? 

• What training programs are available to your employees?

• Are there opportunities for advancement or professional development?

• Would I be able to represent the company at industry conferences?

• Where is the last person who held this job moving on to?

Questions to Ask About Your Performance:

• What are the most important things you’d like to see someone accomplish in the first 30, 60, and 90 days on the job?

• What are the performance expectations of this position over the first 12 months?

• What is the performance review process like here? How often would I be formally reviewed?

• What metrics or goals will my performance be evaluated against?

Questions to Ask About the Interviewer (asking questions of the interviewer shows that you’re interested in them as a person—and that’s a great way to build rapport):

• How long have you been with the company?

• Has your role changed since you’ve been here?

• What did you do before this?

• Why did you come to this company?

• What’s your favorite part about working here?

Questions to Ask About the Company:

• Where do you see this company in the next few years?

• What can you tell me about your new products or plans for growth?

• What are the current goals that the company is focused on, and how does this team work to support hitting those goals?

• What gets you most excited about the company’s future?

Questions to Ask About the Team:

• Can you tell me about the team I’ll be working with?

• Who will I work with most closely?

• Who will I report to directly?

• Can you tell me about my direct reports? What are their strengths and the team’s biggest challenges?

• Which other departments work most closely with this one?

Questions to Ask About the Culture:

• What’s the company and team culture like?

• How would you describe the work environment here—is the work typically collaborative or more independent?

• What’s your favorite office tradition?

• What do you and the team usually do for lunch?

• Does anyone on the team hang out outside the office?

• Do you ever do joint events with other companies or departments?

• What’s different about working here than anywhere else you’ve worked?

• How has the company changed since you joined?

Questions to Ask About Next Steps:

• Is there anything that concerns you about my background being a fit for this role?

• What are the next steps in the interview process?

• Is there anything else I can provide you with that would be helpful?

By Emma Lindsay - May 3RD 2023

Dr. Mads Kaern is a Professor at the University of Ottawa in the Department of Cellular and Molecular Medicine and cross-appointed in the Department of Physics. He has been part of the Synthetic Biology community since the early 2000s and started working in the field with Dr. James Collins on sources of "noisy" signals in gene expression and the engineering of programmable cell behavior by creating "plug-ins" for interfacing synthetic gene networks and natural signaling pathways. His NSERC-funded Synthetic Biology research uses an integrated genetic network engineering approach to study gene regulatory processes and develop artificial gene control systems. Dr. Mads Kaern initiated the uOttawa iGEM undergraduate training program and is the Co-Founder and CEO of Biogroupe Canada. He is also a member of the Cancer Therapeutics Program at the Ottawa Hospital Research Institute, and the Regional Genetics Program at the Children’s Hospital of Eastern Ontario.

What are some of the research projects you are currently working on?

I’m finishing up a big project that is looking at an iGEM inspired program that I launched during the pandemic to get students to do team-based learning similar to iGEM, and it was incredibly successful. This is research that I’ve spent most of my time on for the last three years, and I’m continuing to build the program and improve it in various ways. I’m just about to finish a paper, and I’m really excited about it. I can’t continue to research in this space because there’s no funding for it. So that's a little bit sad, but it's the right thing to do. 

I also have two human health therapeutics projects in collaboration with scientists at the university. In one study, we want to improve the quality of pluripotent neural stem cells for cell-based therapeutics for neuroregeneration. What we want to do is try to use multiplex CRISPR to activate genes that are normally expressed in neural stem cells, but not expressed in induced pluripotent stem cells. That's a big issue because they look like neurons, but they’re not, so they’re not really good for transplantation. Even though these tools have been around for a long time, they’re not good enough yet for these particular applications. The efficiency is not high enough, and we know too little about it. What we want to do is target five or six transcription factors, which means that each of those guide RNAs has to be very efficient. We are hoping to be able to use yeast as a platform and do some large-scale screens to identify highly efficient guide RNAs. That involves a combination of cloning, bioinformatics, and maybe some artificial intelligence (AI) later on.

The second project, the long-term goal is to create microbial biosensor systems. These are complicated scenarios, but they are based on an idea where we have two chimeric antigen receptors that each have a binding site for different areas on a protein or virus, and only if those two come together, we will form a complex that then generates a biological signal. Individually, all those components are known, but they haven't been put together. We want to use that for a biosensor because we've used antigen nanobodies, and we can customize it to anything. We’re starting out with spike proteins because we already have so many different antigens available, so we can see if we can get it to work by optimizing that. Hopefully, we will be able to integrate it with intracellular signaling so we can create synthetic signals to junction pathways. One day, we will be able to have cells that have both the guide RNA machinery that can perform complex regulation of gene expressions and have a synthetic signal to junction pathways. That's where we get into my idea of creating smart biological devices which are cells that know where they are, sense their environment, and make decisions based on those signals. 

What inspired you to get involved in synthetic biology?

I have a very hard time not understanding what I’m working on. So, what I find really frustrating about certain areas of biological research, is that the knowledge that is generated is very incremental and doesn't necessarily yield an understanding of how a system works. You can identify another phosphorylation site, on another protein, encoded by another gene, and you see some effect, but the ability to understand why you see that effect is extremely limited. The only thing you can really do is record what changes when you are disrupting the system. That’s knowledge, but it's not understanding. Understanding the causal relationship and how the system works is still beyond us, and I find that incredibly unsatisfactory. Synthesis is the highest level of understanding, it's the ability to use knowledge or data or information to create something. And that’s why I like synthetic biology. I thought if I can’t understand it by dissecting it, maybe I can understand it by building it. I first did chemistry in Toronto where I worked with infusion reaction systems where you are not just looking at a chemical reaction in a well-stirred environment, but you’re looking at an environment where you have flows, diffusions, turbulence, and all kinds of fascinating stuff that we know is important to life. But, we're still treating systems as these well-stirred chemical reactors, which is kind of nonsense, but it works remarkably well. Then this opportunity came about with the first programmable cells. So as a postdoc, I worked on creating the first prototype of programmable cells. We actually rewired the cellular machinery to respond in a certain way to an external signal. So that was very exciting. And at the time the fab was systems biology, and that is how I got to Ottawa. 

What is BioGroupe Canada?

BioGroupe Canada is a non-profit organization that specifically offers a training program for undergraduates as an alternative to the iGEM competition. Taking some of the key elements of iGEM which is a vehicle for student learning and then addressing some of the deficiencies with the program, not only cost but also the disconnect between institutions and the biotech industry. 

What inspired you to start BioGroupe Canada?

We lost funding for iGEM years ago in Ottawa. In 2018 or 2019 was the last time that I helped the team, and the students were really disappointed because they didn’t get to do much. There’s nothing tangible that they gained from it other than some lab experience. So I created another program during the pandemic which replicates many of those things and addresses some of those issues. 

We also have to change the way we've been doing academics. One of the really impactful moments I had was when I was at the mall changing my Fido phone, and the person that was helping me said he had an Undergraduate degree in Biomedical Science from the University of Ottawa. He looked at me and said it was the worst decision of his life. So here’s a kid, with so few transferable skills in the real world. Probably with a lot of debt and a lot of regret. In these programs at the University of Ottawa, we are graduating around 1000 students, and it is really hard to see the transferable skills for 80% of them. It was embarrassing to me that we can’t do anything better for our students. That's when I realized we have to change how we do things in our undergraduate training. That's why I created this organization. 

I’ve been working with some undergraduate students here in Ottawa because universities don't have resources for this either. It’s kind of like a student club. Hertek Gill has been in charge of developing a number of supplementary learning activities for undergraduates that can help provide and facilitate some of that skills training. The way that we're doing it here in Ottawa they have a student club that we call Bio Connect, and we are hoping to simulate what we had with iGEM where each university has its own cohort of students that would be able to participate in these activities but also propagate them at their own sites. But we're still working on developing these high-quality products, so we don't want to grow too fast because we want to have a strong core that can realistically be distributed. 

You need to do something in outreach in terms of getting students involved early on and that requires a lot of work. That was what iGEM was for, but it's not working anymore. I would not advise any students today to launch an iGEM team. It’s just not worth it. The iGEM program is not structured in a way where you could get funding as a work-integrated learning program in Canada. It's not meeting the bar in terms of what is needed for student training. In many cases, synthetic biology stops. Like in fermentation, you create your bacteria, and then synthetic biology ends, and then other things have to take over in order to build the fermentation scale and marketing. You need to be able to offer training that allows students to reach either way. Let us say synthetic biologists have an entrepreneur mindset, which is inherent in synthetic biology, but also have these tools and skills that look for real-world opportunities and look realistically at translating this. Through iGEM you're not connected to a problem that is relevant to the industry in your area. Who is going to teach you the applications and what is needed for translation if you don't have that connection? You can't translate your skills into something that actually matters outside the academic program. And that's why I’m trying to change that. 

You initiated the uOttawa iGEM undergraduate training program, what do you think is the key to having a successful iGEM team?

Depends on how you measure success. It’s very difficult to be competitive in iGEM unless you are a state sponsored team that puts money into it because they want to advance on the international stage. There’s simply too much work to do in order to be competitive. The idea of winning the competition is something that successful teams need to put out of their mind quite early. The most successful teams in my opinion are the ones that know why they're there. For individual team members, what is it they want to learn? What are the skills and competencies they want to develop? Also, the ability to work within a team, and find a way to collaborate within a very diverse team to be able to accomplish those learning goals while pursuing what appears to be a common direction. I would say that is how I believe students can get the most satisfaction, because they actually get something tangible out of it. Finding good academic advisors is very key, as maintaining social cohesion, and finding a way where everybody can be seen, heard, and contribute to doing work that is meaningful. 

What do you see in the future of synthetic biology?

We have to tap into different resources. What does synthetic biology offer on its own that is unique, that you won't find in any other field? I know we can talk about synthetic biology as being integrated, but it doesn't have anything unique, in my opinion. In order to fund such programs, we have to demonstrate that there's a tangible benefit to those fields. We have to focus on the applied aspect, instead of thinking of synthetic biology as being something that stands on its own. Governments are worried about employment, and companies are worried about revenue. Those are what drives investment in science, research, and development. How can we generate jobs? How can we generate revenue? How can we increase the quality of life? We have to frame it in that way and build up the field based on regional strengths. For example, in Guelph, we would focus on the agricultural side, whereas Sick Kids is already focusing on anti-cancer therapies and oncolytic viruses. That's where I see that it's going. Training institutions will develop incorporating synthetic biology in ways that speak to their local strengths. 

Do you think that Canadian research in synthetic biology is keeping up with other nations? What needs to change?

There is a reason why iGEM is in France, there is a reason why Tom Knight gave up his job at MIT to work at Ginkgo, and there is a reason why Drew Endy moved to Stanford. I think that Canada has done quite well. We have a really good return on investment compared to the U.S. It's not as exciting, it’s not as flashy, and it’s slower. We are lacking in the support where young entrepreneurs can go out, and have money to set up a lab and provide for themselves and their families for two to three years, without any expectations on return of investment. The U.S. is doing that, and it costs them billions of dollars, but that is earned home because one in twenty of those companies is gonna succeed and revolutionize. Some of it trickles down to synthetic biology. But that I think is the core issue, that we don't have the ability to create those entrepreneurial environments within academic institutions. Because if you do it this way, then the young entrepreneurs will come back to academia, and academia will be able to understand what skills and competencies are needed to be successful. That is an enormous hole that we have in Canada, in terms of supporting innovation in the bio-economy sector. We are doing well in Canada, and there is a lot of movement on specific initiatives, CAR-T cells are one, but all of those are transaction based, and once you see there's a big market, the government doesn’t care what you call it. You can call it genetic engineering, synthetic biology, or whatever. If it creates jobs, revenue improves the quality of life and helps Canadians, the government is interested. And it's up to us to demonstrate how synthetic biology is able to contribute to that. I think we need to not be so risk averse, provide more funding into entrepreneurial mindsets, and give young entrepreneurs a chance for a few years to build something they're passionate about and have the skills and abilities to do. But we're always looking for matching funding. We’re missing an entire layer of funding for people that innovate outside of the box. We are relying on existing companies wanting to invest in that. That's not innovation. 

Dr. Kaern’s research in improving the quality of pluripotent neural stem cells and developing microbial biosensor systems are important advances in the field of synthetic biology. His organization, BioGroupe, will provide students with many opportunities to develop their skills training and gain some valuable experience as they continue their educational career, building a generation of professionals whose skills translate beyond their academic program as they enter the workforce. Dr. Kaern’s work can help the field of synthetic biology integrate into many different fields, accelerate innovation, and grow the economy.

EMMA LINDSAY - 31 OCTOBER, 2022

Dr. Rebecca Shapiro is an assistant professor at the University of Guelph, in the Department of Molecular and Cellular Biology. She’s been at the University of Guelph since January of 2018, and runs a research group here where they study the genetics of fungal pathogens. Their research is centred around understanding the important genetics and biology of human associated fungal pathogens. They interface with the synthetic biology world by developing, optimising, and tinkering with new tools that manipulate the genetics of pathogens in order to better understand their biology, how they cause disease, and how they respond to antifungal drug treatments. They develop CRISPR based tools that are used to functionally manipulate the genomes of different fungi, and from there, address big questions in how genetics play a role in the biology of these organisms. 

What are some of the current projects going on in your lab?

We always have lots of projects on the go. In reality, I don’t do any of the real research. I do lots of the thinking, mentoring, and guiding, but there's a fabulous group of graduate students, postdocs, technicians, and folks in undergrads in the lab that all have incredibly exciting projects, and have a lot of cool things on the go. 

One of the things we've been really excited about, with regards to the development of CRISPR technologies and their use in fungal pathogens, is developing new CRISPR tools that allow us to very easily manipulate the genes in a diversity of different strains of a species. When we are talking about fungal pathogens, one of the main pathogens we work on in our lab is Candida albicans, which is a pathogenic yeast. It’s one of the most ubiquitous and common fungal pathogens in the world. It causes yeast infections, which are incredibly common. It also causes systemic bloodstream infections, which are very life threatening and occur in more immunocompromised people. This is a broad pathogen that causes all sorts of disease, and that's our main organism of study. Often when one develops these genetic manipulation tools, the focus is on working on a single strain background. But, with something like Candida, this is a clinical organism, it's found in most people, most of us have Candida in or on our bodies in a commensal state, but it can also cause these severe outbreaks and infections. There's also a real interest in being able to analyse many different strains, looking at different clinical isolates and how they're different from one another. To do this, we've been trying to develop CRISPR tools that are very easy to work with that can then be transported and used in a diversity of different types of clinical isolates or other kinds of isolates of these strains. A lot of the work that we’ve been doing has focused on developing CRISPR regulatory systems. The classic CRISPR, this gene editing idea, is what we often talk about. CRISPR cuts DNA, and we provide it with some sort of repair template to fix the break, and that allows us to incorporate a new piece of genetic materia so that it can allow us to insert or delete something from the genome or actually change the genetic code in some way. That's what CRISPR classically has been. A lot of what we've been trying to optimise recently is these regulatory systems which instead of actually manipulating the genome, allow us to use modified CRISPR to either upregulate or downregulate the expression of genes. Not the actual genetic code, but how much the gene is expressed, which allows us to control things more closely because we can turn down or turn up the expression of a gene. By turning down the expression of the gene, this has the benefit of allowing us to study essential genes, because those ones can’t be deleted, the cell would die, but we can turn down the expression which allows us to study them in a way that we couldn't before. Similarly, overexpression also allows us to study these different kinds of factors. We've been developing these CRISPR interference or CRISPR activation systems, respectively, that allow us to manipulate the expression of different genes to study their function, and has the benefit of being this very simple single plasmid based system that allows us to go into all sorts of different strains simultaneously, and again study gene function, not just in standard lab strains of Candida but also in all sorts of different clinical isolates. 

There is a lot of circulation and news about CRISPR, do you think the public has a good conception of CRISPR?

That is a good question. It certainly is everywhere. I think everyone’s uncle or neighbour has sent them an article about this, or is asking those questions. It certainly entered the public understanding, it won the nobel prize last year, it's working its way into popular media in different ways. I think there's probably a reasonable surface level understanding of what it can do or that it’s genetic editing. There is certainly, at this stage, very prominent human therapeutics that are being developed with regards to CRISPR, so that is making its way into the people’s understanding. I think, as with anything genetic editing, it will always arouse some controversy or some mixed interpretations because of this idea of interfering with natural states or natural biology. There's always towing that line of trying to reach public understanding, while having an understanding of people's rational fears or concerns about things like this. I think it's important to nuance the application of these things, how we use them, when we use them, and how we consult with ethical guidelines. 

What inspired you to get into synthetic biology and focus on CRISPR applications?

When I went to grad school, I did a PhD that focused on understanding the genetics of Candida so I’ve been working in Candida species for a long time. I would say that was more classical microbiology research. When I shifted to do a post doctoral fellowship after grad school, I went to a lab that was much more synthetic biology focused, and the focus there was much more on bacteria. There’s been a lot more rapid uptake of synthetic biology tools and techniques in bacteria for various reasons, they grow fast, they’re easy to work with. I was a person with fungal expertise from my PhD now in a synthetic biology lab, so it was a cool and exciting opportunity to start taking some of these tool kits and systems and try to apply them in fungi. I also started my post doc in 2013 which was right when CRISPR tools came into play. It was the very early days of the development of these tools, so it was a very exciting opportunity to try to co-opt these tools in fungi, where historically we just have far less access to genetic manipulation tools and techniques than we do in other species and other pathogens. It was a good moment in time and an exciting bridging of different expertise. 

Do you have advice for new PI’s that are starting their career?

I think many people would agree it’s one of the best jobs there is. It is such an exciting, and constantly evolving and dynamic job. I mentor students, I teach, I write papers, I write grants, I do interviews. I kinda do whatever I want. I think the advice is, because it comes with a lot of freedom, I think what has been helpful to me is to try to focus on the parts of it I really like the most. Which is not always possible, everyone has to do things they don’t want to do, that’s also part of the job. But, because there’s so much freedom I am able to say yes to opportunities that I think are exciting and interesting. Focus on things that really exploit your expertise. By the time you've reached this stage, you've become an expert in something, so formulate what that niche is and who you are. I seek out, and say yes to opportunities that really allow me to grow in this area, my little corner of the research world. Also, working with people who you want to work with. The job is highly collaborative. I work with many researchers and PI’s but I also work with the students in my group, and there’s a lot of freedom and flexibility to who you want to work with, and that is an amazing perk of this job. I seek out people who I want to work with because we have things in common, and it's fun chatting with them. By seeking out the people that you want to engage with and spend your time with, this allows your work life to be much more fun and enjoyable. 

The Shapiro Lab Research Team

In the long term, what are some obstacles you believe the synthetic biology field will have to face?

Some will come down to regulatory issues and hurdles. How much any of the tools can actually be used as therapeutics, or bred into new crops, or actually make it out into the world and the market. I think that becomes a huge hurdle, which then ties into public perception and the pressure of the people. If people really don’t want CRISPR edited plants in the grocery store, then that's what's going to trickle into policy. Communication with the general population and the policy makers becomes a big hurdle to the field. It’s very different in Europe to the US to Canada. There's very different public perceptions and regulations as a result. I think that says there is room for improved communication. You can see there's a diversity and spectrum of acceptance and perception. 

Do you believe Canada needs any resources to help strengthen synthetic biology research?

I think there's general things that affect a lot of research fields that are not unique to synthetic biology. The constant discussion of how much funding we are injecting into research at the federal level is an ongoing source of concern for all researchers. Relating to that is how much funding exists for graduate students, who are the ones who actually execute the research. This has been an important topic of conversation recently because graduate student stipends that are paid for by federal granting agencies haven't changed in a very long time. The cost of living has increased significantly, so we're sort of hitting a crisis point for overall funding for research, be it for running the research program overall, or for funding and training graduate students specifically. We need money that funds labs, but also money that funds students, and that pays students a fair living wage, because that is changing, and we haven't kept up as a country. I think if we don’t keep up we will lose students, and students are the ones that are executing the research. Those are the folks that are really pushing things forward. If we start to lose the most excellent, prospective students, either they leave to another country or skip grad school altogether, that's going to be a significant issue. Money is an obvious answer, we always need money. But it's been great to see the synthetic biology community in Canada has coalesced. I know there's been big synthetic biology initiatives through Ontario Genomics or Genome Canada, and those funding agencies have started to build more in the synbio area, which is super great. I know that the Canadian iGEM teams have all started to connect more through cGEM and all these other programs. Also, building more conferences pertaining to synthetic biology, I know there's local ones that happen here in Ontario, and I’m sure there’s many others. There’s been all this really great momentum. That’s another important part, building up the research community which allows researchers to connect to one another, and share expertise, and resources. 

Emma Lindsay - October 17, 2022

Christian Euler is the Co-Founder and Director of Strain Engineering of Phycus Biotechnologies. He completed his BSc in Biochemistry and BASc in Chemical Engineering at the University of Ottawa. He recently completed his PhD in Biochemical Engineering at the University of Toronto under the supervision of Radhakrishnan Mahadevan, where he worked in synthetic and systems biology

What is Phycus Biotechnologies?

We are a company that uses synthetic biology to power our fermentation processes. Right now we have a process where we make glycolic acid, primarily for cosmetics, although we are looking at other markets as well. I am in Sydney, Nova Scotia where we've built a demo scale facility up to 1000 liters, and I'm running that project. I’m also working with our employees to drive the development of new products using synthetic biology. The core of what we do is powered by synthetic biology, and we have a lot of fermentation expertise. We run the gamut designing and building the organism, and then bringing it up to a process scale and making a product with it. 

Where did you get the idea to start Phycus Biotechnologies?

It came from my Co-Founder, Vikram Pandit. In his PhD work, he created a technology that could be useful and spin out into something marketable, and I was really interested in that. Even though my research wasn't really related, I had the skills and knowledge to be able to contribute, so we decided to work together. That was back in 2017 or so. At that point we were working in flasks, the 50 mL scale. We've since hired four people, one of them has moved on, we have some employees, and we've scaled up to 1000 liters. But, it really came out of his PhD work. 

What markets are you looking to branch out to beyond cosmetics?

Glycolic acid is a huge commodity chemical that is used in a lot of different spaces. It can be polymerised into polyglycolic acid, which is used in a lot of packaging. It's a next gen polymer, a lot of food packaging people are interested in that because it is biodegradable and it has a lot of useful properties. It's also used to make solvents. Our core mandate is to reduce the carbon footprint of chemical production. Right now, glycolic acid is made from formaldehyde which is a byproduct of oil and gas, which is not great. A lot of solvents that are used for paints and industrial solvents come from glycolic acid. It's also used as a cleaner and disinfectant. It's one of these chemicals that has a really broad use base, which is part of the reason we went after it. Cosmetics are interesting because consumers are very interested in sourcing, whereas in these other spaces, people are less interested in that, it's more about the bottom line. I think in cosmetics, people have a bit more money and time to spend figuring out where the ingredients in their products come from because they're putting them on their face. There’s maybe a little more of a perception of risk there. The consumers in cosmetics are really driving the green transition in that world, and were working with that movement. 

What does the typical day look like at Phycus Biotechnologies?

It’s tricky because there is not really a typical day. Right now, we are in a bit of a transition because we've run our 1000 liter process, and we've gotten all the information out of that process  that we needed to get. That was a demonstration, it was about producing some product for a couple of smaller customers. It was more about generating information so we can then model the scale up to the next scale. Right now we are preparing for a 10x scale up to a 11000 liter reactor. Our typical days are a little bit boring because we are in the office in spreadsheets, putting together information. This includes technical information for engineering teams at the other site and also information for investors. When we are in full production mode we would have two week cycles. The first week we would be doing the fermentation, and we run it with the help of some technicians here. It runs 24 hours a day for the first three days or so, so that means being on shift. First shift is six to two, then two to ten, and then ten to the next morning, which would typically be me. That's on the plant floor doing technical work, working with this huge reactor that’s two stories tall, monitoring it, sampling, making sure that things don’t go wrong, and when they do go wrong, because that's inevitable, solving those problems. The second week would be taking all the data that we generated, processing it, turning it into meaning, and doing process improvement. Because every run you generate a ton of data, we dedicate that time to take all that information and see what went well, what can we do better next time, what tweaks will we make, doing inventory, and preparing for the next run. The person in charge of the synthetic biology work, he's in the lab manufacturing DNA, making strains, testing those strains. When we’re in production mode, we’re doing less or none of that. So it's a bit dynamic. There's a lot of things going on. There's three of us here and two in Toronto. We do have our areas of expertise here, but because there’s only three of us, we end up overlapping a lot and helping each other out, which is great. Our engineer has learned a lot of biology and our synthetic biologist has really gotten into the process side. I think for students of synthetic biology, startups are great environments. It's crazy, fast paced, and there’s lots of stuff going on, but it's a great opportunity to learn everything from end to end. 

What inspired you to get into synthetic biology?

There’s a bit of a long history there. Coming out of high school I went to the University of Ottawa, and I’m not sure if they still have it, but at the time they had this research scholarship where you got to do research in the summer after highschool, going into first year, and then after first year, going into second year. I didn't know exactly what I wanted to do. I was in the biotech program which is a double degree in chemical engineering and biochemistry.  I chose that because I couldn't decide between science and engineering, so I just decided to do both. I got this scholarship, and on the list of professors accepting people that had this scholarship, Mads Kaern was there. His description seemed interesting to me, as somebody just out of high school with very little understanding of the world. I got put on an iGEM project that summer, one of the first jamborees was that fall and I went to it, and I got really excited with the potential of it. In particular, I saw the potential in terms of emissions reduction in all different sectors, but mostly in chemicals. That was way back in 2008, and I've been involved ever since. I’ve had little breaks where I’ve tried different things, but this is what I’ve wanted to do since then, and here I am doing it.

How would you define synthetic biology?

To me, what it comes down to is doing forward engineering of gene circuits and building a microbe that you're interested in having some function. Synbio started with the toggle switch and the repressilator and these interesting academic exercises in the dynamics that we could produce by building gene circuits. Those early tools that were built are maybe not so useful when you're looking at the industrial scale and actually doing something with them. What we do might look a little bit different. The gene circuits we build are not complex. When you are scaling up to actually produce something, complexity is something you want to minimize, it adds risks to your process. I still think we're doing synthetic biology, even though the cloning work we do is much simpler than these really complex gene circuits that can do all kinds of interesting computations. I think there’s a real scale there of complexity, and you might even say that any GMO falls under the umbrella of synthetic biology. I'm starting to think that this idea of “synthetic” doesn't really make sense at all because humans think of themselves as separate from the rest of the world, but we're not, we’re a part of this world. So our interactions with it aren’t synthetic, they're natural. I understand that we need a name for a field so we can recognize it, but I think that traditional notion of building complex gene circuits is maybe limited, and when we think about synbio we can start to include anything where you're making these deliberate manipulations to get a living system to do what you want it to do. 

Why do you think synthetic biology is an important field? What do you think it adds to the world of science?

To me, it really greases the wheels in terms of translation. I definitely consider myself a scientist through and through. I really love doing research and I think that doing research just to generate knowledge is extremely important. I think what's really cool about synthetic biology is it's given the tools and motivation to people to also take what has been done and turn it into something useful. For us, it's about making chemicals in a way that is better for the world. CRISPR work, which really falls under this world of synthetic biology, has the potential to really change the way we approach health. To me that's really neat and maybe that's what differentiates synbio as a separate field. It bridges the gap between knowledge for the sake of knowledge, which is important, and then also using that to create something that is useful for people. I think in the second half of this century, the vast majority of the products we use will come from biology and that's going to be really important and really powerful. I see that as the future, what the power of synthetic biology can bring for us. 

Where do you see the field going in the next few years?

That one is a bit hard to say because I’m not necessarily doing academic research. So, it's a bit hard to know what is coming down the pipeline. What I'd like to see is a lot more work on what happens after you've designed your circuit. You’ve got your gene circuit, it can do a thing, then let's do some industrial work and figure out what that looks like in terms of a process. So I’d like to see more of that happening. What we're seeing now, especially in Canada, there's a small but really dedicated community bringing synbio projects to the world. There's quite a few startups like ours who are doing good work, and I want to see that continue. I want to see them working with academics and universities to be pushing the research to support that. 

The work of Christian Euler and Phycus Biotechnologies in developing formaldehyde free, bio-based, biome friendly cosmetics and personal care products are contributing to reducing our carbon footprint and progressing the development of sustainable chemical products.

EMMA LINDSAY - AUGUST 23rd, 2022

Kevin Chen is the co-founder and CEO of Hyasynth Bio. He completed his Honors Bachelor of Science in Biochemistry at Queen's University and went on to start up Hyasynth Bio. Hyasynth Bio is a synthetic biology company that specializes in creating strains of yeast that produce cannabinoids. Cannabinoids are naturally occurring compounds found in the cannabis plant, two of the most popular being THC and CBD. Cannabinoids have applications in nutritional, pharmaceutical, and recreational-use products. Since Hyasynth specializes in engineered yeast, their platform is adaptable, efficient, and scalable. The yeast is grown in fermenters and fed sugar and water over the course of a few days, after which the end product is extracted and purified. The cannabinoids can be included in a variety of products including pills, oils, and topical formats. The goal of Hyasynth is to customize combinations of cannabinoids and find rare cannabinoids that can be beneficial for a variety of diseases.

What is Hyasynth?

We are focused on genetic engineering of yeast for the production of natural compounds, but specifically cannabinoids. So instead of growing cannabis to get THC and CBD, we grow yeast. We are able to isolate those interesting ingredients, and do that in a much more efficient and sustainable way than growing cannabis. Right now the cannabis or cannabinoid industry is developing in a very bizarre way where on one hand, the science behind it, the endocannabinoid system, is super relevant to all kinds of human health, for example in cardiovascular and neurological aspects. There's so many things that cannabinoids tie into that is going to be a huge topic to research because of what it can do for human health. But at the same time, this system is tied to the cannabis plant and everything that it’s known for, all this narcotics stuff and there's a lot of noise, so the whole space gets looked at in a bit of a funny way. It's tied to this current supply chain and to this whole idea that you have to grow cannabis. For Hyasynth, we're saying we don't have to make cannabinoids using plants, we can do it using synthetic biology, and biosynthesis, and have a regulated, clean, and scalable supply for these things. We started out from scratch where there wasn't a whole lot of research done on these enzymes or the chemistry or anything about them. So it was a lot of basic research that we had to do in those early days to figure out how we actually biosynthesize cannabinoids inside a yeast cell. And on that journey, we came across some super interesting stuff, we developed some really interesting technology platforms. But in the end what we have are strains of yeast that produce CBD at levels that are competitive to the cannabis plant and that's what we’re on our way to commercializing now. 

What does a day to day look like at Hyasynth?

You show up to work, you know who and what you’re working for. We all understand the purpose of the company and we’re all similarly minded where we all care about the future, the technology, each other, and how we progress ourselves in our career paths. There's a lot of mutual respect and a great team environment to work in where people are supportive of each other. There’s plenty of ways to build your expertise, skill set, try new experiments, and learn about the leading ways you can engineer yeast. My job day to day is to send emails and take phone calls. It's not very exciting. But I do love to meet new investors that are looking at synthetic biology that don't really understand it and want to learn more about it because it's part of an ongoing revolution, and that's exciting for me. I also love to hear about all the technology we develop at Hyasynth when we come up with new ideas or when we find some fun way to engineer yeast. That’s all pretty amazing to hear when we get breakthroughs like that. So I hear about those things and tell investors about how cool we are. That's what I do. 

Is there a benefit to using yeast over other techniques? 

In the end, every host organism has its own properties so yeast is one of the generally accepted ones where people know how to grow it and work with it. The genomic tools are pretty widely available and well understood so it's not like you're troubleshooting and falling more into discovery land. It grows quickly and easily, and it's not super sensitive to certain reactive conditions or contamination. So it makes a pretty good overall picture for a manufacturing system. Every organism will perform differently. There's research being done into new host organisms for other things as well, which is all very cool stuff. But, for at least the cannabinoid pathway, yeast is clearly the most efficient organism to host this pathway, and like I said, more so than cannabis itself. 

How did you get involved with synbio?

I got into synbio through the iGEM competition back in 2011/2012 and at the time I was studying biochemistry at Queen's University. I had a super great experience. It opened my eyes a bit to the world of synbio and genetic engineering, which I was always passionate about ever since [I learned about] the idea of DNA and genomics as a blueprint for living things. The concept was always interesting to me. After doing IGEM, I got to know a couple people who were starting a synthetic biology company in Canada, which at the time was called Synbiota. It was through that experience with that start up company, and with these couple Canadian entrepreneurs that were bold enough to start a synthetic biology company here, that got me interested in the idea of starting a company as opposed to joining the industry or joining academia. I thought that was super awesome because I was coming from this IGEM experience of we’re a team, we’re coming up with our own ideas, we're solving these problems, we're thinking about how this actually exists in reality, and I loved all of those things. It wasn't like I had one thing where I loved technology or science, or I loved the effect on society, or the economics of it. In the end, all of it coming together was what I loved the most, and working as a team was also a big part of what I liked about that. After being connected to the start up I also started my masters degree at McGill University and during that degree was where I felt like I was taking a step back cause the environment was such a contrast to what I was already getting excited about. Once the opportunity came around to start Hyasynth, I knew this was what I really wanted to do, and starting a synthetic biology company is the best thing for me. At the time we were among the first companies in Canada to really focus on synthetic biology. That was in the year 2014, where we kicked things off and that's when we got founded. That was also when I dropped out of my masters degree at McGill and did this full time. 

Why do you think synthetic biology is such an important field?

Some people define synthetic biology as some kind of sub-sector of biotechnology as a whole but really, think of synthetic biology as anything genetic engineering related or something that is geared by synthetic DNA. Even every mRNA vaccine we've seen to date or DNA-based vaccines that are helping us with COVID stuff, that’s all synthetic biology. How can you look at that and argue that there’s no impact of synthetic biology? Because it clearly defines the world. The investment towards it is super clear from the human health standpoint. Where it also gets interesting is when you look at the agricultural impact as well. Which is a bit more where Hyasynth applies. We're going to replace an agricultural process with a fermentation process and have a massive benefit to the carbon impact and human health by doing so. There's quite a few companies that do lean in the direction of what other parts of manufacturing or society can be improved by synthetic biology. But anywhere where there's a microorganism or a living thing that can be worked with at the DNA level, there's an opportunity for those things to be improved or better understood through the study of synthetic biology. And even beyond that, you can consider very cool things like the use of DNA and data storage as another branch of synbio that is on its way. There's other fun things with aptamers or RNA ribozymes that fall into the category of synthetic biology because they’re still based on synthetic nucleotides. Those are fields where they’ll change things about diagnostics or changing the analytical chemistry that are on their way too. Synbio is already the root of a lot of what we do. It might boil down to a way of thinking around it. This is a point I do want to stress when it comes to a lot of synbio. When you think about the tools that we have to do research, to do science, to solve a problem, that's where the tools are starting to change a bit. Where you might’ve originally had the idea of chemically synthesizing cannabinoids, that would be the easy way to do it, that's the way we can do it scalably, there's no such thing as a yeast that can produce cannabinoids, that's impossible. But these days, it's actually quite possible and quite easy to realize. It becomes clear how to engineer yeast to do these things. Or even the mRNA vaccine where it was super relevant for COVID stuff, but the original story with a lot of the mRNA vaccines was more around oncology. So the platform was transferable. That’s the interesting thing that you can change about the way research is thought about and how these tools are looked at. Once you can synthesize DNA and use that for a problem, that can be reapplied in a lot of different ways and you start to see a lot of platform based approaches on things. Start to think of DNA or RNA as a tool kit or platform that can be engineered or tailored to whatever need you have. I think that's the big difference between biotechnology of yesterday and synthetic biology of today. 

What do you think is the biggest obstacle for synthetic biology research?

In some ways I feel that the barriers come down all the time. DNA used to be too expensive, sequencing used to be too expensive, the equipment used to be expensive. But everything keeps getting better and cheaper and it's becoming more and more competitive to produce the tools for doing this kind of work. You could talk about society and regulations as some type of barrier. But that's not really a barrier because on some level, you and I define the regulations through democracy. You can vote for people who will put the regulations in place that we think make sense, but it's also our responsibility to drive those things at the same time. In some sense, I could say the major barrier of a lot of synthetic biology stuff is not doing more of it or not trying hard enough to look at the barriers that are preventing you from succeeding. Even the idea of critical thinking around what your barriers are. If your barrier is that NSERC won’t give you enough money for this stuff then get a bunch of professors together and write some big letters to NSERC until you convince them otherwise. If your barrier is really about consumer interest or public interest or public perception on GMOs, then put some readers to that, do the work. I think people tend to throw their hands up in the air a bit and say that they’ve hit a barrier, it’s not a barrier, it’s something that you gotta fix. And you’re the ones that got to do it. There’s a lot of work that has to go into it before it becomes a clear, established process. 

Do you have any advice for a student who is looking to get involved with synthetic biology?

Come work for Hyasynth is one. Two would be go join SynBio Canada. Three is to start your own synthetic biology club at school, or join an iGEM team. Just find ways to get involved and dig into it. Start to do it. You could take the traditional approach and find internships or find professors and start working with them but I think in a lot of cases, especially in this field, a lot of these things are going to be things you start from scratch. Even build a lab in your garage. That's the way a lot of people have gotten into synthetic biology. That's what I would recommend for students. 

Submitted by e-mail to the Pan-Canadian Genomics Strategy Secretariat genomics-genomique@ised-isde.gc.ca

SynBio Canada’s Response to the Pan-Canadian Genomics Strategy Survey

 SynBio Canada is a national not-for-profit with the goal to create, strengthen, and advocate for a coordinated community of enthusiasts, trainees, and researchers passionate about synthetic biology.

 The field of synthetic biology is the application of engineering principles to genomics and molecular biology, to create solutions spanning medicine, agriculture, and industry.

Our vision is to ensure Canada’s leadership in the field of synthetic biology through the development and retention of expertise across the country.

 The following is SynBio Canada’s response to the Pan-Canadian Genomics Strategy (PCGS) survey, launched by Innovation, Science and Economic Development (ISED) Canada. Select responses to specific questions from the survey are presented here. We thank ISED for the opportunity to engage, and we look forward to the release of the full PCGS.

From your perspective, please describe the critical opportunities, gaps and challenges within Canada’s genomics landscape related to adoption and commercialization?

 Opportunities:

Canada has the potential to transform its economy into a bioeconomy.  Within the sectors of health, agriculture, and industry, solutions provided by synthetic biology can have a massive economic impact. Synthetic biology solutions can help to meet Canada's commitments to the UN Sustainable Development Goals (SDGs). This the case for every country in the world, but Canada has some unique opportunities:

 - Canada is already a powerhouse in agriculture and therefore has the opportunity to become the world leader in agri-food biotech innovation & commercialization.

 - Canada has a good foundation for attracting highly qualified personnel (HQP) as it has a high quality of living, recognized all around the world. It is especially attractive for HQP in the biotech area, as the commercialisation of biotech is far easier than within the European Union.

 Demand in commercial lab space should be attractive for commercial real estate investors and the industry is beginning to take notice of. For example CBRE Life Sciences, Lab Occupier, and MIP Labs, which are each Canadian solutions to providing this desperately needed lab space. This engagement between the genomics ecosystem and the real estate industry will accelerate investment in developing more lab space. This can further increase the attractiveness for start-ups and foreign HQP.

 Gaps:

There are several issues that, in our opinion, have been addressed by other countries in a better or more concerted way:

 - There is no dedicated funding specific to synthetic biology/engineering biology in Canada, especially for training and to support commercialization. Other countries go farther than this and have whole national strategies for synthetic biology.   

 - There is a lack of public & government awareness of the opportunities presented by synthetic biology, particularly outside of health & medicine. Recent investments in biomanufacturing are centered on medical applications, which ignores the potential for agriculture and industrial applications.

 - Canada is very good at funding scientific infrastructure/equipment for academic purposes. However, there is a scarcity of affordable & equipped commercial lab space, especially for pre-seed & seed startups. Furthermore, there is a lack of support and training for the people who will use the equipment for industrial purposes. 

 - The private sector is too often seen as merely a source of funding. It may be easy for large corporations to match government funds for R&D to be done by academics, but startups, who are the most innovative and fastest-moving players in biotech commercialization, need non-repayable, non-dilutive, non-match-requiring funds if we want them to stay in Canada and succeed in commercializing their high-impact technology

 - Graduate students in the Life Sciences are often not taught whether and how to commercialize their ideas at the beginning of their career. This is often an afterthought, but instead they should be trained and encouraged early on to foster the development of necessary skills and steer research projects towards the generation of commercializable products.

 - There is a lack of support outside mainstream academic innovation & commercialization cycles. Times are changing and academia is no longer the only source of new biotech start-ups. We need to modernize our commercialization support infrastructure to help non-academic innovators, with a focus on students, entrepreneurial drop-outs, and recent grads

 Challenges:

- The public knowledge of genomics is limited, leading to misconceptions and worries about its use. This is especially the case for everything labeled as Genetically Modified Organisms (GMOs). Such misconceptions will prevent the success of biotechnological solutions that are safer, more efficient and more sustainable than current applications. 

 - Academia is still inert towards promoting entrepreneurship. University tech transfer offices are generally very slow to respond and, together with  the equity taken by universities, this frustrates entrepreneurs and makes investors hesitant. The cultural differences between the worlds of academia and entrepreneurship create tension that prevent commercialization. Whilst lip service is often paid, graduate students who pursue entrepreneurship commonly face great resistance from their academic peers & supervisors instead of support & encouragement. Even though most graduate students do not stay in academia, their training, CV and success matrices are defined by professors and departments, which have no incentives to promote non-academic skills and training. Quite the contrary, participation in non-scientific events and workshops is seen as time that the student should spend on doing academic work. Students should get more training about IP and how tech transfer at universities works. Additionally, a bigger focus on industry, entrepreneurship and applications during their graduate career

 - The life sciences community is often siloed into either industry or academic associations/events, making it difficult for students to get exposed to industry and to develop their entrepreneurial skills and spirit. Furthermore, the laboratory space is limited and expensive, making it difficult to commercialize ideas and expand them beyond academia. WIthin academia, students are siloed into different faculties with very minimal inter-faculty and interdisciplinary opportunities meaning that students in the sciences are not exposed to ideas such as design thinking from the engineering faculty or business planning from the Business Faculties. This means that students do not have the cross-disciplinary skills they need to successfully create their own biotech start-up.

 - The Venture Capital (VC) community in Canada is risk averse, in particular regarding life sciences. Non-dilutive government funding could help to de-risk early-stage biotechnology to make it more attractive to Canada’s risk-averse investor community.In this regard, the restrictions of funding organizations like Genome Canada from directly supporting for-profit corporations is counterproductive to their goals of accelerating genomics commercialization.

 - Canada's science policies are often created on the “follow-the-leader” principle, with the US (and sometimes the UK) as examples. As a result, Canada's public and private genomics funding is always 5 years behind, and an order of magnitude too small. We need transformative, visionary funding for talent and ideas. 

How can these opportunities, gaps and challenges be addressed? This could include through the PCGS or other mechanisms.

 - All aspects can be addressed by funding public communication initiatives to clearly communicate the benefits of genomics technologies. Framing investments into biotechnology and synthetic biology as investments in sustainability can overcome the perceived dichotomy between biotechnology on one side and “natural”, “green”, and “organic” solutions on the other. We can replace or enhance the production of most chemicals, foods, medicines via biotechnology, while making their production more sustainable.

- Dedicated funding of at least an additional $50M/year to synthetic biology/engineering biology fundamental research. This is comparable to investments made by the US, UK, and Australia (relative to GDP), which would mean Canada is at least on par. A more significant investment ($100M/year) would mean Canada could win the competition for global HQP. Such funding should include a public investment program similar to the US SBIR program, that provides non-dilutive funding to commercialize transformative genomics technologies, on the order of $200K - $2M per company.

 - A national training program for recruiting graduate students and postdocs, including training on how to commercialize their research and/or start a company. This has been implemented in Australia, which led to a self-sustaining community and further company creations and investment downstream. The programs should focus on biotech entrepreneurship among students instead of reinforcing the traditional profile of tenured research professor spinning out or licensing their academic research. Such a training program should be paired with guidelines for universities on how to commercialize biotechnology, with standard procedures and defined amounts of equity that a university is allowed to take. Of further help would be the creation of a handbook about IP, tech transfer, sources of public funding and programs for commercialization in Canada. All this should be determined by external experts and not only the university administration itself.

 - A recognition that opportunities in life science extend far beyond human health and that in fact many of the easier & higher-impact innovations are in food, agriculture, materials, industrial chemicals, computing/IT, and other non-biomedical applications. In particular, the Canadian biomanufacturing strategy must be expanded beyond medical applications. There is a massive opportunity for food and chemical production using engineered microbes and such products can reach the market faster. A massive investment in biomanufacturing infrastructure that is not exclusive to or even primarily intended for biomedical commercialization could be a first step towards unlocking this potential. Next to the equipment and funding, biomanufacturing training is needed, in particular fermentation scale-up (from 1 - >100 liters). Canada does not only need visionary entrepreneurs, but also HQP that are able to do the scale-up of such visions.

 - An immigration program that attracts life science HQP to Canada. The success of such a program depends on a biotechnological infrastructure, which is addressed in the points mentioned above.

 - Increased focus on developing transferable skills in students during your post-secondary education so that they are better prepared for work outside of academia. This would require providing students with an interdisciplinary education where they are able to easily take classes from other faculties to supplement what they learn in their degree. This could be complemented by programs and events to connect MBAs with life science PhDs. Finally, there should be support for a national network of bio-entrepreneurs (from trainee, to start-up, to SME, to larger company professionals).

How can the PCGS use regional expertise to inform a pan-Canadian approach to genomics that will advance shared national priorities and strengthen Canada’s position in the global bioeconomy?

 Based on a variety of interactions between the synthetic biology community and the regional Genomics Centers, we frankly believe that focusing too much on regional expertise is the wrong strategy.  It will result in a perpetuation of the current economic landscape of Canada. Rather than trying to craft a pan-Canadian approach catered to regional interests, the strategy should be visionary. The PCGS must lead organizations, industries, and people to where we should go. This may be a very different regional landscape than what we have now.

 There is no harm in leveraging regional expertise and diverting it towards the desired future. For example, using the chemical engineering expertise of oil patch workers to develop and lead industrial bioproduction facilities in western Canada. However, we believe that the current specializations of Genomics Centers creates confusion for stakeholders. In the example of industrial bioproduction, entrepreneurs have to figure out to which extend their local Genome Center (e.g., Genome Prairies) or the specialized Genome Center (Genome Ontario in this example) is the right counterpart for their needs. We need to promote & support bottom-up development of the bioeconomy. Individuals and private organizations have the best understanding of the opportunities & challenges in their local areas and need to be incentivized to seize/address them.

What needs to be in place to support stakeholders within the Canadian genomics ecosystem to work better collectively in order to improve adoption/commercialization of genomics across Canada and globally?

- A national biofoundry, or rather a network of biofoundries, that centralize expensive automation equipment and expertise, but make it available to anyone in Canada to use for scaling up their genomics research and developing commercial products. This should include available access to 100L+ fermentation for microbial production upscaling.

 - Non-dilutive funding for:

a) hiring and accessing lab space for startups 

b) accessing or building biomanufacturing infrastructure, for SME biotechs, especially for the deployment of sustainable solutions.

 - There should be incentives for harnessing genomics solutions/products for non-biotech companies. The BioPreferred mandatory federal purchasing system in the US is a good example, but in the Canadian version it should be extended to all private and public enterprises.

What are the strengths and weaknesses of Canada’s genomics-related infrastructure?

 Canada has excellent genomics core facilities, expertise for sequencing and good funding for expensive equipment (initial investments). Additionally, the federal government has recognized the need for improved biomanufacturing. However, the weaknesses Canada should address are:

 - DNA synthesis is the key driver of the modern bioeconomy and Canada does not have any high-volume providers of synthetic DNA. To truly become leaders in genomics & biotech, we need at least one (ideally several) competitive DNA synthesis companies

 - There is a clear lack of fermentation experts and upscaling facilities, leading to many great ideas/companies getting stuck at scaling up past a few litres of production. It is also difficult to find out where in Canada biomanufacturing/fermentation facilities are and what they offer.

What are the challenges and opportunities in accessing and using genomics-related infrastructure? It may be useful to consider different sectors and regions.

 Challenges:

- Lab space at universities is tightly controlled, and very difficult or even impossible to rent. The rentable lab space is also unevenly distributed, localized mostly in the Greater Toronto Area (GTA) and prohibitively expensive.There is only one publicly funded biofoundry offering services to scale up and help commercialize genomics solutions (the Concordia Genome Foundry). This biofoundry does not receive consistent funding from, meaning it is in a boom-bust cycle between grants and funded projects, making it difficult to hire and retain HQPs, purchase and maintain equipment etc.

 - Sequencing technologies are rapidly reducing in cost, both for purchasing the equipment as well as running it. There is a transition to decentralized sequencing, leading to diminishing Return Of Interest (ROI) from sequencing facilities.Therefore, sequencing core facilities are at risk of being replaced and surpassed by decentralized sequencing (i.e. Nanopore). The sequencing core facilities and their funding entities should monitor this development closely and ensure that the facilities specialize in services and technologies that cannot be provided by decentralized sequencing.

Opportunities:

- Nationally funded biofoundries could centralize expensive automation equipment and expertise in local hubs (e.g. provincial capitals), enabling anyone in Canada to access this equipment on a cost-recovery basis. Similar centers exist for pharmaceuticals in Canada (i.e. adMare) but not for applied genomics or synthetic biology. In comparison, the Agile Biofoundry in the USA is directly funded by the US Department of Energy. Competitive grant funding supports innovative companies/projects and enables them access the biofoundry. A similar system should be set up in Canada.

From your perspective, what are the main opportunities and challenges to developing, retaining and attracting genomics-related talent in Canada?

 Opportunities:

- Canada leads the world in standard of living and human rights, making it an attractive place to live.

 - Companies in Canada are very willing to partner with universities/colleges for placements/industry relevant training.

 - The NSERC CREATE grants have spurred new genomics-oriented training, and generally been very successful at recruiting trainees.

  Challenges:

- Wages in the life sciences in Canada are stagnant, and not competitive compared to the US. This is especially true for trainees and postdocs, which leads to an exodus of HQP towards the US, as outlined by a report of the Expert Panel on the Labour Market Transition of PhD Graduates.

 - Publicly funded equipment and facilities are not maintained with additional funding. As a result, equipment falls into disrepair and this undermines the efforts to generate and maintain the expertise to run the equipment moves, preventing the training of highly needed HQP for the bioeconomy. 

What should be done to ensure that, as Canada's genomics ecosystem grows, it is increasingly representative of our diversity and supports equity and inclusion?

 Exposure to genomic sciences and biotechnology should be spread more evenly across Canada instead of being concentrated within only a handful of universities and cities. This leaves many Canadian children, especially from rural areas and First Nation reserves at a disadvantage, as exposure and how genomic sciences can benefit their local community is missing. This could be addressed by university satellite campuses in smaller towns and biomanufacturing programs in colleges, which would also address the lack of fermentation scientists and technicians. 

 A good example of how this issue can be addressed was given in Alberta, where High Schools received funding and support to build their own teams in the iGEM competition, the worldwide student competition in synthetic biology. This exposure led many participating high school students to subsequently pursue a degree within the life sciences. If genomic sciences and the bioeconomy are the future of Canada, then for the next generation(s) the thought of becoming a genomic scientist must at least be at par with the thought of becoming a doctor or an engineer. 

Please describe the strengths and weaknesses of Canada’s genomics-related data infrastructure? To what extent does the current data infrastructure, from data generation to management to utilization, support the data needs of stakeholders?

 Strengths:

- The Compute Canada DataBase (CCDB) offers significant computing resources and excellent training for the academic community. Here, Canada really excels at teaching HQP with a life science background the necessary computer skills to use bioinformatics for their research and product development.

 Weaknesses:

- There is a lack of a standardized knowledge base of what synthesized DNA is available and shareable within the Canadian Academia. Knowing what these sequences are, where they physically exist, and if they can be freely shared is very difficult and delays research efforts or makes them redundant. The nonprofit Addgene and the private company Ginkgo have centralized its management of genomic data, making it available across different stakeholders and fields of research. Such a model could be implemented by publicly funded data.

Given significant advancements in technology development, what can the Government of Canada do further to leverage and optimize the use of genomics data?

 Canada is host to a diverse array of ecosystems and biodiversity. This is a wealth of genomic data that should be part of the public domain. With the decreasing cost of DNA sequencing, every effort should be made to make DNA sequences obtained from the Canadian wilderness public domain, ensuring that anyone can access, learn from, and use these sequences. Ideally, this would lead to a public database of genomic sequences from Canadian ecosystems.

What areas should the PCGS focus on in order to maximize the socioeconomic, health, and environmental benefits for Canada from the commercialization and use of genomics technologies and innovations within Canada and internationally?

 Using the UN SDGs as a framework for investment in genomics technologies and synthetic biology. We published a policy memo on this topic here: https://www.sciencepolicyjournal.org/article_1038126_jspg180106.html

 In particular, there should be major incentives to develop and commercialize technologies for bioproduction of chemicals and products, including food, commodity chemicals, fuels, specialty chemicals, and pharmaceuticals. Bioproduction of these proven chemicals and products will reach the market fastest, while making a major impact on sustainability.

What activities would enable stakeholders within the Canadian genomics ecosystem to better adopt and commercialize genomics technologies and innovations?

 Frequent events to showcase technologies and research, as well as incentives for non-bio-based companies to use genomics-based products.

 What should the Government of Canada and the Canadian genomics ecosystem focus on to better support the commercialization, adoption and utilization of genomics technologies and innovations?

 In general, the Government of Canada and the Canadian genomics ecosystem has made large investments in sequencing technologies. Sequencing technologies are project agnostic, and a useful tool, but they do not directly further the adoption and utilization of genomics technologies. 

 Instead, the focus should be on synthetic biology, which more directly aims to develop products in agriculture, medicine, and industry. Synthetic biology represents a maturation of the fields of genetic engineering and biotechnology. Synthetic biologists design and build biological systems to solve problems. When funding and efforts are put towards applied solutions, there is a more direct path from academic research/funding to a commercial product. 

How can the Canadian genomics ecosystem work better together, including through policy and program supports, to ensure that as genomics technologies and innovations come to fruition, they are adopted by Canadian researchers, businesses, academia, government and the public?

 Public awareness campaigns to clearly explain the benefits of genomics technologies. There was some success with this regarding mRNA vaccines for COVID. Canada should be vocal and proud about the genomics technologies being developed here, and the potential they have for Canada's economy and efforts towards sustainability. 

 What specific gaps, barriers and challenges limit Canada’s ability to be a global leader in genomics technologies and innovation?

 University tech transfer offices are a major barrier to commercializing technologies in Canada. There should be a clearing house for publicly funded innovations that desire to be commercialized by the inventors. This clearing house should entail standard policies on IP, equity taken by universities, etc. for publicly funded innovations.

 In your opinion, which sectors offer the greatest opportunity for the potential adoption of genomics in the near-term (i.e., next five years)?

- Production of foods, food products and additives. This includes the production of alternative proteins and flavorings by microbes

 - Valorization of waste products: converting a waste product or chemical into something more valuable

 - Sustainable industrial biomanufacturing via precision fermentation: engineering microbes to convert sugar into fuels, commodity chemicals, specialty chemicals via fermentation

 What are the next steps needed to achieve their potential?

 1.     Non-dilutive funding for SMEs and entrepreneurs

2.     Lab space for proof-of-concept development

3.     Lab space/biomanufacturing infrastructure  for scaling up/production

Are there any considerations that we have missed or elements we should explore further when addressing the top priorities for the PCGS?

 The Genome Canada enterprise and regional Genome Centres deserve significant acknowledgement for their 20+ year leadership in this space. However, we believe that the regional Centres are not the best model for Canada. The vision and priorities of each Centre are very different. For example, Ontario Genomics has a keen interest in synthetic biology, however the other Centres have not strongly supported the field. Advocacy/lobbying for genomics issues is also disparate and generally unclear across these Genome Centres. Is this their responsibility? If not, who’s is it?

 Rather than having separate Genome Centres, each with competing priorities and initiatives, Genome Canada should function as the sole unifying organization, for funding of genomics research across Canada.

 The PCGS must also recognize the need for an independent, not-for-profit association of synthetic biologists in Canada. SynBio Canada was specifically founded to serve as such, and was recently incorporated as a federal not-for-profit. We seek to create, strengthen, and advocate for a coordinated community of enthusiasts, trainees, and researchers passionate about synthetic biology. Genome Canada does an admirable job funding research across Canada, but lobbying the community's interests is not its priority, and is too often beholden to the politics of the day. Hence, an independent organization run by those in the scientific and entrepreneurial community, can best set a clear vision for the application of genomics technologies in Canada.

What should Canada’s top priority be for the PCGS?

 The PCGS should put a priority on synthetic biology, as it is by definition “applied genomics”. The Canada Synbio conference organized by Genome Ontario highlighted that the synbio community is focused around startups and entrepreneurship. Furthermore, it is cross-disciplinary by nature. For example, in the field of biotechnological production, projects and setups can easily shift between applications in agriculture and medicine, based on demands. A well funded synthetic biology sector is capable of reacting to a multitude of challenges in an agile way. 

 Dedicated, long-term, significant funding for synthetic biology should be a priority, both for discovery-driven research, and non-dilutive funding of SMEs:

1.     Dedicated means that it should clearly targeting synthetic biology research and commercializing applications.

2.     Long-term means a 10+ year commitment.

3.     Significant funding should be in the area of public funding for discovery-driven research at $100M/year and public, non-dilutive funding of SMEs at $500M/year, to be competitive with the Synbio programs of other countries.

Sincerely,

Fabian Rohden, Science Policy Lead

Samir Hamadache, Vice President

Benjamin Scott, President

EMMA LINDSAY - AUGUST 10, 2022

Dr. Brian Ingalls is a professor at the University of Waterloo in the Department of Applied Mathematics. He is also cross appointed to the Departments of Biology and Chemical Engineering. Dr. Ingalls’ research is focused on synthetic and systems biology. His lab is the Ingalls Quantitative Cell Biology Lab at the University of Waterloo, where his group utilizes mathematical and computational tools to build and analyze kinetic models of biomolecular systems. Their focus is on intracellular networks and heterogeneous microbial communities. Currently, their projects are centered on model-based design of synthetic bacterial gene regulatory systems.

How did you get into synbio?

 When I was finishing my PhD, I was working with feedback control systems and my advisor pointed me to some recent stuff that was being done in reverse engineering a biochemical regulation. I went to a talk by Michael Elowitz, who presented the repressilator. I had no biology up to that point, and I was just blown away that it was possible to do that kind of engineering project in that space. And then I got lucky, and I ended up in a postdoc group doing engineering and biology.

What are some of the projects currently going on in your lab?

Bacteria mediated cancer therapy. This is something that most people have never heard of. In the mid 1800’s, it was observed that sometimes cancer patients got bacterial infections and if they survived, sometimes it helped with their cancer. People played around with it, but they did not really understand what was happening. And then, chemotherapy and radiotherapy were developed, and it fell off the radar because people had better ways to address cancer. It's come back a little bit, people are renewing their interest in it because of the means we have now to manipulate the bacteria doing this. The basic idea is that anaerobic bacteria solve in a particular way the targeting problem. In cancer therapy, one of the biggest problems is targeting cancer cells, and not targeting healthy cells. The feature that bacteria mediated cancer therapy was taking advantage of is that a lot of cancers produce these solid tumors, and these solid tumors have trouble being properly oxygenated, so you end up with this mass of cells that have poor access to oxygen. This produces an anaerobic environment inside the person's body. So, if you have cells or spores of anaerobic bacteria, you introduce them into a person. Those cells, if they find their way into the anaerobic core of that tumor, can proliferate and propagate. And if they don’t, they just get cleared since they are inert. So that is an interesting way of solving this targeting problem. People have been looking at this over the last couple of decades in terms of engineering those cells so that they can do different things. Naturally, as they grow, they can chew out some of the cancer cells in the area and elicit an immune response because there's this infection going on so that can help with the cancer remission. But also, you can engineer the production of drugs or prodrugs. We’re looking at the Clostridium species and we're doing some engineering with that to do two things: one is to introduce a quorum sensing mechanism so that the activity can be turned on when they reach a significant population density in this tumor environment and have targeted activity in particular areas; the second thing is we are also looking at increasing their air tolerance so that they can proliferate a little more than they normally could in that environment to have the effect that we need. 

Optimal experimental design. It was established one hundred years ago in the early 20th century for linear descriptions on how experiments depend on the set up of the experiment. The basic idea is that if you have a particular objective for your experiment and you have a limited set of resources that you can expand your project on, then which resources should you choose to address the goal of understanding the system in a particular way? In the linear space this is a nice theory and applies when you make these assumptions about a system's behaviour linearity, which is not typically the kind of thing you see in biomolecular networks. If you take the same theory and try to apply it to more complicated linear scenarios, for example dynamic systems, then you have the same kind of questions. Which experiments should I do? One basic question first is if you’re taking a time series, where do you choose your time points? That's the kind of questions that one can address. So recently we’ve developed tools and some software packages along those lines that essentially allows folks to do that kind of analysis. 

An example of the optimal experimental data. Graph by Nathan Braniff, PhD Candidate

Behaviour of bacterial communities. We're looking at baby versions of bacterial ecology. Bacterial ecology is very complicated and it’s very difficult to characterize what is going on in those systems. What we do in the lab is we set up very simple communities and start with characterizing their behaviours and working towards things that are more complicated. We are looking at things like horizontal gene transfer, phage infections, and more generically inhibition in terms of a diffusible toxin release from cells or a contact dependent effect. The tool we have for characterizing these systems is time lapse fluorescence microscopy. We have a set up that allows us to image the entire population in a single focal plane and we add fluorescent markers to these cells to indicate their state. We can run these experiments for twenty-four hours or more and we can watch the cells propagate and interact. What we have alongside that data is the characterization of the data in terms of these dynamic models. One opportunity is to use this modeling structure to understand how these systems behave, for instance to infer things like conjugation rate, growth rate, and effective conjugational growth. The goal here is to eventually use these models for model-based design of manipulation of these systems. These systems are in lots of different environments and being able to manipulate them sounds promising.

Image by Aaron Yip, PhD student.

You use mathematical and computational tools for your projects. Are these techniques  common in synthetic biology?

The main mathematical tool the group uses is kinetic modeling to characterize system behavior and explore possibilities. That can be either the reverse engineering of systems to better understand what is there, or from a forward engineering perspective, model-based design. We can build models with some degree of accuracy in terms of prediction and that’ll allow us to explore design space much more cheaply than you could running batches and batches of experiments. I would say it's fairly common. There are lots of people that go into life science and have an aversion to computation. That's changing. There was a time when a lot of people in biology spent their whole careers and did very little computational work. The human genome project was a breakthrough for bioinformatics being identified as a key part of molecular biology. This kind of work is a bit more esoteric. Standard bioinformation is about things like genome analysis, sequence alignment, working with static data, and there's a lot of that data available. This kind of work requires more data to put these kinds of descriptions together. That kind of data is hard to collect, it is expensive to run these experiments so it's often not the first thing people do. I like to think it is becoming increasingly more common, but I wouldn't say it's very common. But there are lots of projects where it's an important piece and it's becoming a more valuable tool as people recognize that the data is available. The basic idea is that the systems are very complicated so in every other branch of science when you hit a really complicated system you need to turn to these tools to understand. 

Are there any resources that Canada needs to help strengthen the field of synthetic biology? Where do you think Canada can improve?

Canada's economy is based on resource extraction which comparatively doesn't require a lot of R&D. That's been the basis for the economy since the country was founded. That is in part what has led to a sort of risk aversion in terms of investment, both private and public, so Canada is often lagging when it comes to new technologies and risky technologies. We do have certain strengths for sure. The educational system is great at producing people who can do this sort of work, and who are interested in this sort of thing. I think there's a lot of promise, and there certainly could be more delivery on that promise if we had more investment.

Are there any applications or techniques in the synthetic biology field that you’re excited for?

There's a lot of short term promise in biomanufacturing. Improving biomanufacturing is an iterative improvement, and so that does seem to be an area that the community is continuing to embrace as where there will be lots of impacts of synbio. One of the basic questions is about the release of organisms. So, if you're going to make an organism and you're going to use it, you have to set it free into the environment. People are understandably nervous about that. There are lots of discussions, and I don't think there's going to be any problem there. If you can have your advantage in the lab or the factory, and you never have to have that discussion, then it makes life a lot easier.

Do you have any advice for someone that wants to get involved in synthetic biology?

I could say two things. One is networking. There are groups and communities such as iGEM, and there’s always an opportunity to reach out. There are lots of opportunities to get involved even at the high school level. That’s something people should keep in mind. And the community is very welcoming and happy to have people interested at all stages. The other thing I would suggest in planning an education that could lead in this direction is being open and trying to embrace ideas across disciplines. A lot of educational programs are very siloed and disciplinary. Especially as an undergrad, that's how the program is set up and that's what you do. You take the courses you need to take. Seek out opportunities to expand that toolbox. Given that synbio is a relatively young field and a very interdisciplinary field, the best positioning one can have as a junior researcher, or someone interested in entrepreneurship is to get exposure to as many as those things as possible. So do a little bit of computing or entrepreneurship or life science or bioinformatics. Often one must be proactive about reaching out cause standard programs are typically very siloed and disciplinary. 
Dr. Ingalls’ research in developing mathematical models is important for the field of synthetic biology. These models can help predict behaviours of intracellular networks and cellular communities, help build an understanding of complicated systems, and help further the progress of synthetic biology research

Fabian Rohden (Science Policy Lead) and Dr. Benjamin Scott (President) have published a editorial as part of the Canadian Science Policy Centre’s 2022 series Building Resilience During International Crisis.

The editorial examines the paradox of openness, whereby the openness of nations is both the cause and solution to several ongoing international crises. This paradox also extends to Canada’s bioeconomy, where the openness of genomic data and infrastructure must be carefully considered.

Read our editorial to learn more: Facing the Paradox of Openness to Build Resiliency in Canada’s Bioeconomy.

Hertek Gill - April 22, 2021

Design of the clarifier insert for wastewater treatment tanks created by the BioEnvo team and presented at the cGEM 2020 conference.

COVID-19 has affected the world in many ways but one effect of the lockdown that has hit university students hard was the sudden loss of many summer employment and co-op opportunities. Many students rely on these opportunities to fund their education and to gain vital job experience in their field of study. Due to the lockdown, many traditional student employers were, unfortunately, unable to host students over the summer. It was amidst these unprecedented times that Dr. Mads Kaern of the Faculty of Cellular and Molecular Medicine at the University of Ottawa started the BioExperience program with support from the University of Ottawa and BioTalent Canada. This new program would provide over 50 students the ability to work over the summer as well as the opportunity to gain the experiences and skills needed to initiate a career in biotechnology with an emphasis on the engineering of biological systems at the cellular and molecular level.

The BioExperience program was an interactive and collaborative learning experience in which teams of 6-8 undergraduate students from a wide variety of programs and faculties worked together on various self-guided projects related to synthetic biology. The 2020 BioExperience Program consisted of 7 different teams which investigated various topics ranging from removing microplastics from wastewater to creating a 3D bioprinter.

Students in the program were involved in every step in the research project from formulating the research question, creating a plan, interviewing and hiring other students, organizing and distributing the workload, and summarizing the results into publication-quality reports. This allowed for a large potential for growth as students learned to independently do the various tasks associated with running a research project.

The group setting with fellow undergraduate students created an environment where discovery and trial and error were promoted as everyone was learning how to organize and manage a research project together. This created a very collaborative and encouraging environment where everyone was able to speak during lab meetings and have their ideas considered. The inter-faculty nature of the groups also provided many students with their first exposure to working in interdisciplinary teams as most other group projects at the undergraduate level are done with peers in the same program. This allowed all the students to experience working with people with a completely different knowledge base and using these different backgrounds to the advantage of the group as a whole. This skill set will be very beneficial to all the students in future endeavors where they will have to coordinate with different departments at their place of work.

Another aspect of the program that was very influential in making the experience rewarding were the various training sessions held throughout the summer on topics such as doing research using the library’s virtual resources and how to cite work. These workshops helped teach important skills in an environment where they would be immediately applied, allowing students the opportunity to use and refine the skills without forgetting them.

COVID-19 testing kit designed by the COVID-ENG Team.

Throughout the summer each student conducted both self and peer-assessments of their fellow teammates. These assessments allowed students to understand their strengths and weaknesses so that they could understand what they could work on improving over the summer. Self-reflections were important as they allowed the students to think about what they have accomplished so far and what they personally see as their next steps. Students were then able to compare their reflection with the anonymous assessments their peers made of them to understand if they missed something. These moments of reflection ensured that everyone stayed on course over the summer and could utilize the remaining time to improve themselves as much as possible.

At the end of the 4-month program, every team submitted their work in a series of reports, schematics, and diagrams. The final day of the BioExperience Program was the Closing Ceremony. This one-day event featured presentations from each team, speaker panels as well as prizes for the various teams. This event was a culmination of everyone’s hard work and allowed everyone to showcase their work to their peers, faculty, and family.

 After the summer, one of the BioExperience teams was chosen to present their work at the first annual Canadian Genetically Engineered Machines. Here the BioEnvo team was able to capture a gold medal and the award for the “Best Collaboration” for their close discussion with experts in the field, other research groups, and universities. The BioEnvo team consisted of 3 subteams which each worked on a different aspect of the project. The three sub-teams included the Microplastic Filtration sub-team, which designed a clarifier insert for wastewater treatment tanks; the Microplastic Remediation sub-team, which determined the necessary steps to process the collected microplastics, and the Microplastics Biodegradation sub-team, which focused on enzymatic processes to degrade microplastics. The final product of this project was a theoretical system that can remove microplastics from wastewater, using magnetite powder to create magnetic clumps of microplastics, which could then be easily collected. These collected microplastics would then be taken to a separate facility where they could be degraded by PETase enzymes inside a specifically designed Bioreactor facility.

The team not only focused on the science behind the project but also developed a viable business plan and pitch presentation to show potential investors. The pitch focused on the business aspect of the BioEnvo project and the benefits, both environmental and financial, that would come from the implementation of this project to remediate and recycle microplastics from the Ottawa River.

In the end, the BioExperience program was an experience like nothing else a student at the undergraduate level experiences in university. This program’s blend of problem-based learning with collaboration amongst an interdisciplinary team allowed every single student to develop many skills that will be vital to them in the job market. This program provided an experience that will have a profound impact on how students perceive the job market and their place within it. As a student who has experienced the first iteration of the BioExperience program, I would strongly encourage students to take the opportunity to be a part of this program as it will help them improve a multitude of skills and will leave them better prepared for anything that lies ahead. If your university does not offer such a program, strongly consider discussing this with the administration as a BioExperience-like program would be very beneficial to all students in terms of the experiences it provides to its participants.

Ammielle Wambo Becker - April 22, 2021

Despair and anxiety are not uncommon feelings among young people these days. As high school students, we deal with many sources of stress, from parental pressure and high expectations to mounting workloads. It's not easy to juggle all this, not to mention the growing concerns about the future, whether it's because of the climate crisis or the coronavirus. But I am optimistic about one thing: synthetic biology.

https://pixabay.com/users/qimono-1962238/

I learned about synthetic biology in September 2020. Over the summer, I first learned to code in Python, then in JavaScript, and now in Java. I enjoy the creativity of debugging code and solving problems and the collaboration of participating in hackathons and competing as a team. When I first heard about the development and application of computer science techniques to biology, I was hooked. The exciting idea of programming a cell with the code of life, DNA, as I would with any other programming language, led me to biological computing.

Biological computing is concerned with the creation of biocomputers, i.e. biomolecules capable of performing calculations. I dove into DNA digital data storage and synthetic biological circuits as a way of demonstrating the computer-like properties of biological systems. Although I didn't know it at the time, I was just covering a small area of the field of synthetic biology.

I don't really know what about synbio is special to me. Maybe the field is just so emerging and I feel I can make a real impact. Maybe it's such a multidisciplinary and broad field that I don't have to choose a specialty yet. Maybe it's really a matter of optimism: synthetic biology shows great promise. Or it is a blend of all these reasons and more. I can see myself tinkering and engineering with biological elements for a long time.

I think the COVID-19 lockdowns have been both a blessing and a curse for my learning journey. On the one hand, more synthetic biology webinars and conferences are being held virtually than ever before, and thus I don't have to worry about cost or travel distance. I can gain invaluable insights and meet other people through Zoom! On the other hand, although I would love to gain the technical experience of working in a wet lab, I have never set foot in one. I’ve learned everything I know from articles, papers, and videos, as well as from insightful conversations with researchers and professionals. 

It is often discouraging that so many opportunities and courses are reserved for post-secondary students, but I understand why. Because we lack the experience and knowledge to participate in technical courses and challenging events, high school students are rarely the target audience. Yet I always wonder why there are hardly any opportunities for us to get involved in biotechnology, to gain this necessary experience and knowledge. Few people around me (and even fewer people my age) have ever heard of CRISPR or synthetic biology. Despite the online learning content for beginners, entering this space can still seem intimidating and daunting to many. And even after taking the huge first step of outreach and awareness, I think that presenting enrichment materials and opportunities for a strong and diverse future biotech workforce is often missing. Even if young people know what synthetic biology is, how can they foster their interests? How can they pursue these fields beyond the classroom?

A good start would be to provide young people with mentorship and advice from researchers. I also think that research projects and placements play a key role in exposing students to potential career paths and supporting their interests. And why not launch courses with live lessons and virtual communities for young biotech enthusiasts across Canada to connect with others and share interesting articles and papers? Why not hold biotech challenges, case studies, or sprint-like events for students of all levels? While I cannot speak to the logistical or financial requirements of providing such opportunities, they could only empower young people to engage responsibly with synbio, to express diverse perspectives, to take an interdisciplinary approach, and to pursue careers in the Canadian bioeconomy. 

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Thanks for reading my article! I’m Ammielle Wambo Becker, a Grade 10 student in Ontario, interested in the intersection of biology,  technology, and society. Feel free to connect with me on LinkedIn, check out my website, or follow me on Twitter :)

A policy memo drafted by members of the SynBio Canada Executive Team was recently published in the Journal of Science Policy and Governance. The memo entitled “Invest in Canadian Synthetic Biology to Meet Commitments to Sustainable Development and Support Economic Recovery” adds to the chorus of calls for dedicated funding of synthetic biology in Canada.

The memo was initially written before the COVID-19 pandemic, then updated many times to stress how important synthetic biology is for our future.

Abstract: Canadian post-COVID-19 economic recovery efforts have been framed around values aligned with Canada's commitments to the United Nations Sustainable Development Goals (SDGs), primarily concerning environmental sustainability. The field of synthetic biology (synbio) offers many innovative ways to achieve these goals while growing the economy. Here, we discuss the opportunity for Canada to become a leader in clean technology applications of synbio. Investments in synthetic biology, which has traditionally been underfunded compared to other countries, will have beneficial impacts on the environment while driving Canada's post-pandemic economic recovery.

Direct link: https://www.sciencepolicyjournal.org/uploads/5/4/3/4/5434385/grue_etal_jspg_v18.1.pdf

Fatima Sheikh - January 26, 2021

While the cGEM 2020 conference provided a platform for Canadian iGEM teams to showcase their work, this event also fostered conversations on many aspects of synthetic biology with students, industry leaders, and academic professionals. The conference was kicked-off by Dr. Bettina Hamelin from Ontario Genomics discussing the biological innovations that are being pushed forward as a result of the COVID-19 crisis. This inspiring keynote set the tone for what was 2 days filled with many different talks and important discussions on the vast applications of synthetic biology in Canada. 

On day one there were a series of interactive workshops  that allowed students to explore different avenues/aspects/components, important in the field of synthetic biology. The After iGEM team, directly from iGEM HQ, held an important workshop on scientific communication! To put it simply, research does not matter without effective communication. Scientific communication is required at every level of research whether it be in the beginning when acquiring funding, throughout while recording results, and especially at the end when relaying this information to stakeholders and the public. A strong emphasis in this workshop was put on knowing your audience. Is this information being presented to other professionals in the field, or is it being relayed to the public? Breaking down the language used is critical to ensure understanding of the material and knowing your audience can ensure that there are no misunderstandings. As members of the growing synthetic biology community, part of our responsibility is to ensure proper engagement of the public and this was highlighted by the After iGEM team and discussed throughout the remainder of the conference.

On day 2 we began with a series of fireside chats, one which included Dr. Benjamin Scott (SynBio Canada) along with Avalyne Diotte and Pierre Oliver (Policy Horizons) discussing what they’ve learned from the ongoing biodigital convergence webinar series. Together, they answered a number of questions and ultimately highlighted the potential of synthetic biology techniques and approaches that can be used to build on existing knowledge and infrastructure within Canada. But, how do we make this transition to the use of synthetic biology and its different applications in a way that engages all the important stakeholders? They suggested that part of it will come down to good science communication and with the recent pandemic, health and innovation are at the forefront of public discussion, providing scientists of all disciplines an important learning opportunity.

Later on during the day, a series of panels were held, one of which covered the topic of synthetic biology education. This conversation was moderated by Bi-ru Amy Yeung (cGEM co-director and co-founder), and included expert voices from Patrick Diep (CSBERG co-director and founder), Dr. Vincent Martin (Concordia), Magda Pop (MindFuel), and Orly Weinberg (Concordia). They highlighted the synbio education landscape in different regions of Canada and the progress that has been made over the past few years both at the high school and the post-secondary level. Moving forward, they encouraged the integration of project-based learning and re-framing human practices, referring to the social and ethical impacts of research, to improve integration with other domains of synthetic biology research. With students being an important part of the synthetic biology community future, a strong emphasis on educational programs that highlights both the technical skills along with other important aspects, such as science communication, will equip synthetic biologists with the tools to contribute to the bioeconomy.

This recap of the cGEM conference wouldn’t be complete without a discussion on the Equity, Diversity, and Inclusion in Synthetic Biology panel. It featured Dr. Trevor Charles (Waterloo), Kelcie Miller-Anderson (MycoRemedy), Dr. Nika Shakiba (UBC), and Peivand Sadat Mousavi (University of Toronto)  and was moderated by Dr. Rebecca Shapiro (Guelph). Together, they fostered a discussion on roadblocks experienced by minorities and how each of them overcame their own obstacles. These individuals are inspirational, to say the least, with their stories providing proof that  anything is possible with a strong support system. Suggested advice to young students and prospective synthetic biologists included making connections early and finding supportive mentors. Mentors can provide insights into how to elevate your career but are also important for navigating potential barriers. While there are strong efforts toward making the field of synthetic biology more diverse and inclusive, there is still a lot of work that needs to be done and will require each of us to do our part in creating a more equitable and diverse community. 

This conference was wrapped up with a keynote by Dr. Ryan Pillipe from Genome Canada, where he shared insights into how students can  contribute to the Canadian bioeconomy, followed by reflections from Amy Yeung (UofT), Jehoshua Sharma (Guelph), and Luana Langolis (Western) on the conference and future of synthetic biology. We think it’s safe to say this year's conference was a success, and while we only highlighted a few sessions from the conference, every session had fostered important discussions between students, researchers and industry professionals. As we continue to grow this community and leverage synthetic biology to improve society, effective knowledge translation and engagement of the public as well as active efforts to create a more equitable and diverse community, are going to be important drivers of this growth.

Thank you to everyone who attended this conference, if you missed any of the amazing sessions you can find the recordings on the cGEM Youtube Channel. Be sure to keep an eye out for next years events and initiatives by following @cGEM_2020

List of cGEM 2020 Workshops

• Pitch Fundamentals by Forest City SynBio

• Scientific Communication by After iGEM

• Scientific communication is extremely important with 6 main keys

  • Stakeholders: people depending on the research

  • Scientific method: this includes disseminating results

  • Public perception 

  • Funding

  • Communication skills

  • Sustainability 

• Lean Business Model Canvas by Danielle Rose from SynBio Canada

• Translational Synbio by Synlogic

• Inscripta Keynote by Chad Whitman

• Biodesigning our Future by Ginkgo Bioworks

• Digital Bioconvergence by Synbio Canada and Policy Horizons

• Community Science by Open Science Network

• Equity, Diversity, and Inclusion in SynBio Panel

• Environmental Sustainability in SynBio Panel

• Canadian Start-Ups in SynBio Panel

• Canadian Education in SynBio Panel

• Genome Canada Keynote by Ryan Philippe

• cGEM Keynote by Jehoshua Sharma, Amy Yeung, and Luana Langlois

Nicole Leblanc - October 29, 2020

While many events and conferences were cancelled this year due to the pandemic, the first-ever Canadian iGEM (cGEM) conference was held on October 3rd and 4th. With over 240 participants registered, 10 iGEM teams presenting, 4 workshops, multiple panels, and keynote speakers, this event fostered important synthetic biology discussions. This inaugural trainee-led conference was organized by iGEM members across the country, led by  iGEM alumni and synthetic biology enthusiasts, Jehoshua Sharma, Bi-ru Amy Yeung, and Luana Langlois who saw a need for a trainee-focused synthetic biology conference.

The year of 2020 will certainly be remembered for generations to come as the time when ‘unprecedented circumstances’ interfered with plans for the future on a global scale. This was no different for Canadian iGEM teams as many were forced to make the difficult decision to not participate in the (rather expensive) international competition this year. 

Having recognized the educational value of the experiential learning opportunity facilitated by the iGEM competition, the cGEM steering committee sought to develop an all-Canadian version of the competition at no cost, which aims to contribute to the creation of training opportunities for young trainees in the country and better reflects the organization’s values: academic ingenuity, entrepreneurship, fostering public trust, and promoting interdisciplinary action. To this end, the organizers developed their own judging criteria, which placed a stronger emphasis on entrepreneurship. Also, many teams were unable to access labs as they normally would and so the cGEM competition criteria was focused on project design, collaboration, and peer review. 

The cGEM criteria was used to judge the teams not participating in the iGEM competition, while the teams  attending the online iGEM jamboree were judged by the iGEM Medal criteria so as to minimize the duplication of efforts for the latter teams. From the teams that are not participating in the iGEM competition this year, three teams were awarded a gold medal, the University of Guelph, the University of Ottawa, and the University of British Columbia, one team was awarded a silver medal, McMaster University, and one team awarded a bronze medal, the University of Toronto.

Of the teams that are participating in the iGEM competition this year, there were 2 teams awarded a gold medal, the University of Waterloo and Queen’s University, one team awarded a silver medal, Lethbridge Collegiate, and two teams awarded a bronze medal, University of Calgary and Lethbridge high school.  In addition to medals 4 special awards were given out including best academic innovation to McMaster University, best entrepreneurship exploration and best scientific communication to University of British Columbia, and best collaboration to the University of Ottawa

With synthetic biology-based projects ranging from engineering various crops to developing software to help predict vaccine targets, the iGEM teams demonstrated a breadth of knowledge that can be readily applied to address imminent global and local issues, leaving all of the attendees nothing but impressed. Have a look below to see what each team worked on! More information including project presentations can be found at the cgem2020.ca website.

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The Teams

McMaster: Built a mathematical model of a bacterial population carrying antibiotic resistance genes subjected to sustained antibiotic pressure due to the antisense oligonucleotide (ASO)-mediated silencing of antibiotic resistance genes! They also worked on validating the time to failure, frequency of specific and non-specific mutations that lead to resistance and explored clinical trials to better understand ASO cytotoxicity and patient adherence.

Guelph: CRISPR for Climate Resistance. They are working on controlling the expression of plant genes such as cold tolerance genes or drought resistance genes to enable the plant to survive in harsh conditions. Also, in an attempt to democratize science, they have designed an affordable shaking incubator and with further testing, intend to make this model available to other iGEM teams so they can build their own too.

Ottawa: Developing a solution to remediate plastic pollution in freshwater environments. By developing a bioreactor and utilizing a plastic degrading enzyme, PETase, water from wastewater treatment plants can be more thoroughly processed and plastic extraction can be improved. The broken down plastic could be recycled and used to make biogas or more plastic products.

Toronto: Generating more efficient plastic-degrading enzymes by combining rational design and machine learning. The team has proposed a bioreactor for textile recycling in Toronto, diverting them from landfills, by generating more stable and efficient variants of current plastic degrading enzymes, such as PETase, MHETase, and LLC, and integrating these into E. coli.

UBC: Designed VPRE (Viral Predictor for mRNA Evolution), a software tool that simulates evolution to predict genetic mutations in viruses. Applying this software to emerging viruses, the evolution of protein sequences can be predicted and can help inform pre-emptive vaccine development that targets conserved viral proteins. 

Lethbridge Collegiate: Engineering potatoes to express antimicrobial peptides as a solution to problems concerning agriculture. Having potatoes express antimicrobial peptides effective against Fusarium fungi, would eliminate the issue of infections during potato storage. Another possibility is to express antimicrobial peptides with known health benefits to help boost consumers' immune systems, increasing public resilience in the event of a pandemic.

Calgary: Developed, OVIITA, a food-safe beta-carotene rich strain of yeast that is modified to secrete enzymes to increase beta-carotene production and to help combat poor vitamin absorption for the prevention of Vitamin A deficiency. This would empower communities to cultivate their own renewable source of vitamin A locally. The team has also developed the Randle cell, a portable Vitamin A deficiency diagnostic device.

Lethbridge High School: Designed tPectinACE, Targeting Pectin to Accelerate Compost Enzymatically, a synthetic system to accelerate compost degradation. The team aims to create a system that can be utilized in households and in large-scale composting facilities to help eliminate the methane gas produced from composting which contributes to climate change.

Queens: Developed a biosensor for the quantification of chronic kidney disease (CKD) biomarkers such as parathyroid hormone and fibroblast growth factor 23. The current monitoring method in Canada is through blood samples every 6 weeks and this time frame makes it difficult to provide patient-specific treatments. The biosensor would allow for frequent monitoring and early CKD detection, leading to better patient outcomes.

Waterloo: Designed REMINE, a column bioreactor with metal-binding proteins to remove toxic heavy metals from electronic manufacturing wastewater. This also allows for heavy metal recycling as they are very valuable. REMINE system can be customized to target specific metals, making it adaptable to the environment it is used in.

Best of luck to Queen’s, Waterloo, Lethbridge Collegiate and high school, and Calgary upcoming iGEM competition, we know you will make us all proud! And make sure to keep an eye out for Part II of our cGEM summary coming soon.

Danielle Serra - February 27, 2020

During my K-12 education subjects such as mathematics, biology, and art were always taught separately, with little interaction between them. But in the real world, problems and projects are rarely so focused on a single discipline, which is why interdisciplinary teaching and problem solving serves as a unique and important opportunity for students well before they enter post-secondary school. Synthetic biology tools are well suited to interdisciplinary teaching in classrooms, as they intersect many areas of study such as life sciences, engineering, and design.

Figure 1: BioBits™ Bright is a synthetic biology learning kit that provides exposure to molecular biology and engineering techniques at a beginner level of understanding (Reprinted from [Science Advances] Stark et al 2018).

The creation of an educational biology kit, jointly worked on by University of Toronto synthetic biologist Dr. Keith Pardee, will enrich a student’s educational experience by exposing them to biological engineering techniques. BioBits™ Bright, is a just-add-water synthetic biology kit where cell-free reactions are used to express fluorescent compounds as visual stimulation. Classrooms are typically limited in the projects that can be performed such as due to biosafety regulations, cost, or availability of equipment. By addressing such limitations, students can further their engagement in biology by using this kit.

BioBits™ Bright

This educational kit offers a low-cost opportunity for schools to implement synthetic biology into their curriculum. Designed to be user-friendly for any untrained operator, BioBits™ Bright uses FD-CF (Freeze-dried, cell free) reactions which synthesize protein in vitro. FD-CF reactions work by introducing freeze-dried pellets that contain many of the biological components that exist in living cells such as RNA polymerase or translation initiation factors, without the need for actual living cells. FD-CF reactions are also stable and can be performed at room temperature without compromising the results of the experiment. A library of 6 main fluorescent protein variants as seen in Figure 1(A), were chosen as the main fluorescent colours for individual expression. Students are then able to visually link molecular concepts and ask deeper questions as to how they may occur.

Two modules were developed for use with the FD-CF reactions and the fluorescent variants as the core components for BioBits™ Bright.

Module I: Changing the level of fluorescence

This first module helps students to understand protein synthesis. As seen in Figure 1(B), various concentrations of DNA template are titrated to the FD-CF reactions. By allowing the students experiment with the different concentrations of DNA template, they should come to the conclusion that there is a link between the amount of DNA template and the level of florescence that is ultimately produced. This experiment allows students to better grasp the idea of the central dogma in molecular biology by conceptualizing the idea that DNA template may act to initiate protein synthesis. The levels of florescence as the outcome for Module I, qualitatively teaches students that DNA plays an important role in the ability to produce protein.

Module II: Designing, building, and testing

Using BioBitsTM Bright, the design, build, and test cycle is implemented to create unique designs using varying levels of fluorescence (Reprinted from [Science Advances] Stark et al 2018).

Module II next enables students to build upon their knowledge from Module I and create their own in vitro project. Introducing the design, build, and test (DBT) cycle, it will introduce students to synthetic biology and engineering concepts (Figure 1(C)). Students will be able to rehydrate the FD-CF reactions with any of the 6 main fluorescence variants and any desired amount of DNA template in order to produce the required fluorescence to build their project. During the first trails of Module II, participants were given the creative freedom to construct their own in vitro program. As seen in Figure 2, some participants created designs resembling things like the rainbow, the periodic table, or even Connect Four®!

Built for accessibility, BioBits™ Bright will help engage students in the classroom and introduce them to the field of synthetic biology. By allowing the student to produce a project of their interest, the end result will combine biology with art and creativity.

For more information about BioBits™ Bright, check out https://www.mybiobits.org

 References

Stark JC, Huang A, Nguyen PQ, et al. BioBits™ Bright: A fluorescent synthetic biology education kit. Science Advances. 2018; 4(8). https://advances.sciencemag.org/content/4/8/eaat5107

Danielle Rose - February 3, 2020

Group photo of Bio SynSys attendees - photo by Danielle Rose

If you want to learn about cell free, Bio SynSys is the place to be.

In November I had the opportunity to attend Bio SynSys in Bordeaux, France as the representative for SynBio Canada. We were invited to participate in a panel discussion featuring members from a number of Synthetic Biology Organizations (including France, Europe, Germany, and the UK). Bio SynSys is a joint effort between the German and French SynBio Organizations (including the Max Planck SynBio research group and SynBio France) to showcase the exciting research going on in these two countries. 

Backdropped by beautiful French architecture ensued 3 days of inspiring talks on topics ranging from microfluidics to re-designing the plant photosynthetic pathway. Thanks to the Max Planck Institute’s focus on bottom up biology, I got a crash course in cell free systems and the awesome opportunities they open up with regards to rapid pathway optimization.

As the conference continued, I got to hear some amazing talks, but one in particular has still stuck with me. Every once in awhile when you attend an event like this you hear a talk that make you giddy with excitement at the amazing new potentials for the field that have appeared before your very eyes. The talk by Marieke Scheffen from the Max Planck Institute for Terrestrial Microbiology was without a doubt one of these. Through her presentation she brought us through the steps her team had taken to engineer a completely novel carboxylase not found in nature in order to develop a new biosynthetic pathway. And, if this wasn’t cool enough, the newly developed tartronyl-CoA (TaCo) pathway is already being used by a partner company to improve the way that plants conduct photosynthesis, eliminating carbon waste.

It was really cool to share what we are working on in Canada at an international conference, and it was exciting to see all of the work being done across the world by other SynBio organizations. Our panel discussion resulted in an interesting chat about what is needed in the years to come with regards to education for those wishing to pursue a career in SynBio. The debate mainly came down to whether or not it was better to have a program specifically designed for engineering biology, or if the field was too multidisciplinary and broad for this to work and if we should just focus more on fostering independent learning through easier to access materials online.

As the conference drew to a close I said au revoir to the new friends I had made and headed back to Canada, armed with new ideas on how to improve our synbio community. As different as our countries are it's exciting to see how similar the synbio community is across the world, and it really inspires me for what we will be able to accomplish in the years to come.

Danielle presenting on SynBio Canada - photo provided by Alicia Magnanon

SynBio organization panelists - photo provided by Alicia Magnanon

Making new friends over croissants and SynBio - photo by Danielle Rose

Large scale active-learning-guided exploration to maximize protein expression in vitro - Angelo Cardoso Batista, photo by Danielle Rose

Patrick Diep - December 13, 2019

The Canadian Synthetic Biology Education Research Group (CSBERG) logo - contributed by Patrick Diep

I believe it was on Twitter when I saw someone tweet that synthetic biology (synbio) was a subject that should stay within the realm of graduate students and postdocs in academic research labs because it was “too hard for undergrads”. This is a common sentiment in synbio, and it wasn’t my first time hearing it, but it struck a nerve because I was heading to Boston in a few months for my third time judging for iGEM (International Genetically Engineered Machine, an annual synthetic biology design competition) . I thought about how iGEM was my entry point for research during my undergraduate studies and about how awesome some of these iGEM projects can become. I’ve attended five iGEM jamborees now and have had the chance to witness how synthetic biology projects flourish from high school, undergraduate, and overgraduate (i.e. graduate student-based) teams. Synbio is not too hard for undergrads.

Gatekeeping synthetic biology hampers its big promises to help tackle a variety of issues in fundamental science and real-world issues. I understand the opinion that one needs to enter synbio with their own expertise in order to more effectively work with other experts, and having a specialized undergraduate program helps with that. But instead of restricting access because of the “too hard for undergrads” notion, maybe we can consider whether there is anything we can change at the undergraduate level to make the transition to synbio graduate work and industry more streamlined. Not multidisciplinarity, but interdisciplinarity.

So, I asked myself a big question: how does one teach a highly interdisciplinary subject to a mixed audience composed of undergraduates from experimental, computational, engineering, social sciences, and humanities backgrounds? Participating in the iGEM competition provides students with a strong situated learning experience where students from all these backgrounds must work together to fulfill the iGEM competition medal criteria, but there is limited research that explores the learning dynamics in iGEM design teams. Based on conversations with iGEM judges and professors, and my own observations, iGEM undergraduate alum become excellent graduate students. How can these success stories be translated into elements of synbio curriculum design within and beyond iGEM?

The CSBERG Instructor Team - contributed by Patrick Diep

I decided to investigate this big question, but I knew I could not do it alone. With Katariina Jaenes’ help, a colleague and friend from Professor Keith Pardee’s lab, we created and delivered an introductory synbio workshop to the undergraduate iGEM Toronto design team at UofT, in May 2019. It was well-received, but we learned very fast that teaching synthetic biology requires a team of experts, and that two experimentalists like us could not pull it all off. So, I later formed the Canadian Synthetic Biology Education Research Group (CSBERG) in August to investigate this question. CSBERG is a graduate student-led “teaching R&D” program for synthetic biology at the undergraduate level. We consist of iGEM Toronto/Calgary/Waterloo alum (many now graduate students), BioZone graduate students, and colleagues from multiple universities in Ontario and Québec.

CSBERG has a clear deliverable that everyone on this team is working toward: a 1-month intensive workshop series (May-June 2020) to teach a mixed audience the knowledge and tools required to plan and execute a synthetic biology design challenge. Based on our collective understanding of synbio at the graduate level and from previous iGEM competition experience, we are placing a special emphasis on developing leadership, teamwork, communication, and collaborative skills to empower the students to work better in groups. We are also placing a special emphasis on integrating the various topics that we will be teaching so that students can understand how tools in other disciplines are used. To guide us in developing the specific workshop content, we are conducting a survey of all 2019 Canadian iGEM design teams to identify educational gaps that we could address in our workshop series. Finally, to gauge our teaching effectiveness, we are designing educational experiments with assistance from OISE (Ontario Institute of Studies). All this work will go through the Office of Research Ethics (at UofT) for approval, and we hope to publish our findings for our stakeholders.

Overall, CSBERG’s existence is a response to the notion that synbio is “too hard for undergrads” – it’s not. More time and concerted effort must be put into critically breaking apart traditional pedagogy for related disciplines (e.g. biochemistry, molecular biology, bioethics, chemical engineering, etc.) and re-building it with contemporary teaching strategies and integrated feedback from relevant stakeholders. We envision our work informing the development of upper-year courses that help senior undergraduate students interface their speciality knowledge and tools with those of other experts in order to address synthetic biology design challenges from an interdisciplinary approach.

To keep up to date with our work, we encourage you to follow us on Twitter. CSBERG values far-fetched untested teaching ideas (we literally have a document for this), so if you’re especially passionate about teaching courses/content related to synbio, we invite you to message us at csberg.biozone@gmail.com for support, or perhaps a collaboration! We are also looking for financial sponsors and advisors (i.e. principle investigators) to support the growth of CSBERG, so please e-mail us if you are interested.

Cheers,

Patrick

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Patrick Diep is a 3rd year PhD student under Professors Krishna Mahadevan and Alexander Yakunin in BioZone, a bioengineering cluster in the Department of Chemical Engineering and Applied Chemistry at the University of Toronto. He is genetically engineering microbes to remove and recover heavy metals from mine wastewater and is program director for CSBERG, which also provides oversight for the revitalized iGEM Toronto design team.

Kenza Samlali - December 12, 2019

iGEM 2019 Judging Panel. (Picture: iGEM Foundation, Justin Knight)

How many biology degrees offer students an opportunity to collaborate with other disciplines, or design and perform lab group work at all? I know that during my undergrad I never had the chance to design my own experiments, let alone collaborate with students from other faculties. This is traditionally reserved for your Masters thesis or PhD work.

But what happens if you build a support network for (under)graduate students from all over the world who wish to do so? The field of synthetic biology seems to be the ideal testing ground for such an activity, covering engineering principles, characterization, standardization, safety and human practices. 

Luckily, I’m about 16 years late with this idea, and the reason why synthetic biology is built on these elements, is partially thanks to groups of students taking part in iGEM. Since its inception in 2003, the iGEM organization (international genetically engineered machine), has played an important role in the education and structure of the field of synthetic biology, turning the focus on multidisciplinarity and engineering principles to address critical problems in our community with synthetic biology. With a yearly competition - the international genetically engineered machines (iGEM) competition - iGEM stimulates hundreds of (under)graduate and high school students worldwide to complement their education with a self chosen self-directed project.

The importance of iGEM in the field of synthetic biology can’t be understated. The freedom an iGEM project hands to undergraduate students leads them to learn design thinking strategies, fundraising, marketing, hardware and software design, communication skills and long-term planning. The methods of teaching and training promoted by iGEM, in the shape of a fully student-run multidisciplinary project, develop sharp minded students with soft skills a traditional scientific education would never offer them. Many companies originated from iGEM projects, and the ‘AfteriGEM’ network has been able to send ex-iGEMers to important international conferences where the iGEM community is invited, being experts in the field.

Calgary’s excitement after the announcement of their finalist prize. (Picture: iGEM Foundation, Justin Knight)

This year, 14 Canadian collegiate teams and 1 Canadian high school team were accepted to participate in the iGEM Giant Jamboree at the Hynes Convention Center in Boston, a gathering of teams from all over the world marking the end of the yearly competition. From October 31st to November 3rd, the teams presented their work to fellow iGEMers and an expert judging panel. Again, this year I had the pleasure to be part of this judging panel. In total, nine Gold medals, two silver medals, two bronze medals, 4 awards and numerous additional nominations were awarded to the Canadian teams. This is also the first time in history a Canadian team is a finalist - Calgary being first runner up in the undergraduate division. Canada has never performed this well at a Jamboree!

Our Canadian iGEM projects are mostly self-funded, and completely extra-curricular, with passionate students who clearly want more than sitting behind their desks. Something is happening and students can’t sit still anymore. We want to build, invent, run companies, collaborate, and be believed in. This is what iGEM has given our students, from fifteen Canadian institutions. Canadian students want to shake up the way they learn, leaving an impact on our communities. I’m extremely excited thinking about how far this generation will move the field of SynBio, with a little bit of flexibility and increasing support from our education system.

Congrats to all teams!

UBC students explaining their project to a judge during poster sessions. (Picture: iGEM Foundation, Justin Knight)

Award Summary 

1 Finalist

9 Gold, 2 Silver, 2 Bronze medals

Best Food and Nutrition Project, Best New Application, Best Software Tool, Best Integrated Human Practices Undergraduate

Teams Overview

British_Columbia

Medal: Gold

Project: UBC developed a method to prevent paralytic shellfish poisoning (PSP) - a neurotoxic illness that has devastated coastal indigenous families that rely on seafood as a main diet.

Calgary during their final presentation on stage - (Picture: iGEM Foundation, Justin Knight)

BrockU

Project: Flip recombinase activity is binary and thus cannot be precisely activated in time and space. Utilizing light-sensitive protein interaction domains termed “magnets”, the Brock University iGEM team has developed a light-sensitive optogenetic variant of Flip recombinase that can be controlled in Escherichia coli with exquisite spatiotemporal precision.

Calgary

Finalist, first runner up, Undergraduate

Awards: Best Food and Nutrition Project, Best Software Tool, Best Integrated Human Practices Undergraduate

Award Nominations: Best New Basic Part, Best, New Part Collection, Best Model, Best Poster, Best Presentation, Best Supporting Entrepreneurship, Best Wiki

Medal: Gold

Project: Calgary addressed the green seed problem - a big problem in the Canola oil industry. Green canola seeds causes financial harm to farmers and oil producers. The team tackled several parts of the Canola oil manufacturing pipeline: improving seed production with a weather predicting program,  improving grading practices with hardware to calculate seed grade, produced 6GIX enzymes for extraction of chlorophyll and designed improved variants, and designed several enzymes to convert chlorophyll into an anti-fungal peptide.

Concordia-Montreal

Awards Nomination: Best Presentation

Medal: Gold

Project: The Concordia team set their eye on Fentanyl, an opioid painkiller, and the leading cause of accidental opioid overdose as many recreational drugs users are unaware that their drugs are laced with it. Quantifen, as the Concordia team calls it, is a non-invasive wearable biosensor based on a yeast biosensor, for the detection of fentanyl in sweat.

Guelph

Medal: Gold

Project: Team Guelph University developed an antibiotic biosensor as to measure Tetracycline in animal products, to tackle the problem of antibiotic use in the livestock industry. E. coli was used as a model organism, turning pink upon the detection of tetracyclin.

Lethbridge

Medal: Gold

Project: Lethbridge tackled a problem the pharmaceutical industry has dealt with for a long time: oral delivery of insulin. By using a microalgae called C. merolae, the team was able to solve this problem. By engineer an insulin metaboilic pathway in it, these acid pH resistant algae can now be ingested.

Lethbridge_HS

Students of Lethbridge High school explaining their project. (Picture: iGEM Foundation, Justin Knight)

Medal: Silver

Project: Canada’s only high school team decided to use CRISPR to build a diagnostic system that could identify pathogens and provide accurate antibiotic treatments, thus decreasing the misdiagnosis and spread of antibiotic resistant bacterial strains.

Northern_BC

Project: Northern British Columbia team is the second team this year that decided to chose to address the opioid crisis. They built an opioid biosensor in Saccharomyces cerevisiae that can be used to test non-opioid recreational drugs for opioid contamination prior to consumption.

Queens_Canada

Awards Nomination: Best Diagnostics Project

Medal: Gold

Project: The Queens team designed a novel portable immunoassay to detect tetrahydrocannabinol (THC) – the active ingredient in marijuana. They used recombinantly expressed antibody fragments, which are conjugated to fluorescent molecules.

Toronto

Awards Nomination: Best Manufacturing Project

Medal: Gold

Project: Toronto designed circularised PETase enzymes for PET hydrolysis into environmentally-harmless terephthalic acid (TPA) and ethylene glycol (EG) outside the cell. They additionally developed new methods to generate thermostable PETasemutants.

UAlberta

Medal: Bronze

Project: The UAlberta iGEM team created a portable detection system to replace the current time consuming detection method of Nosema ceranae disease in honey bees. They did so by designing a system comprised of M13 phage labelled with a chromoprotein and displaying a ligand specific to N. ceranae spores. Based on the colour intensity of the diagnostic paper strip, the severity of the hive infection can be assessed, thus democratizing diagnosis and facilitating effective treatment of N. ceranae.

ULaval

Awards: Best New Application

Award Nomination: Best Model

Medal: Gold

Project: Team ULaval created a device, called A.D.N. (Airborne Detector for Nucleic acids, DNA in French) to rapidly detect small concentrations of airborne pathogens. The device relies on a novel microfluidics-based DNA extraction method, and detection of target DNA sequences by molecular sensors. 

uOttawa

Medal: Gold

Project: The University of Ottawa team wished to tackle the obstacles of the lack of expertise and financial constraints many iGEM teams have. They have produced easy-to-read and video protocols, and multiple BioBrick library that offer compatibility with E.coli and yeast, or Golden Gate assembly.

Waterloo

Medal: Silver

Project: The Waterloo team engineered rhizospheric soil bacteria Bradyrhizobium diazoefficiens USDA110 to have the ability to form root nodules with soybeans in the presence of the herbicide linuron. Usually, herbicides have a negative effect on rhizobia, which offer nitrogen delivery to most farmed plants, reducing the need for fertilizers.

Western_Canada

Medal: Bronze

Project: At Western, students developed a versatile platform for the degradation of a wide range of emerging contaminants consistently found in wastewater. They did this using a self-assembling catalytic bacterial biofilm capable of degrading these contaminants.

Check out last year’s Canadian team’s performance in our blog post here.

Laura Prochazka - October 28, 2019

Medicine is entering a new era where chemicals will be replaced with engineered cells that perform human defined functions; where transplants from human donors will be replaced with de novo (in the laboratory) engineered tissues and organs; where damaged tissues and organs will be regenerated inside our body; where diagnostics will detect diseased states prior to appearance of symptoms; and where our genome is edited to prevent incurable genetic diseases. Medicines are going to be precise, safe, preventative and curative. Medicines are going to be made by design and synthetic biology is going to be a key enabler to realize these new approaches in medicine.

Figure 1: Medicine by Design banner. Photo credit: Neil Ta

Medicine by Design Invests in Synthetic Biology 

Figure 2: (a) Attendees of the MbD Synthetic Biology Discussion Group and (b) how they define / think about synthetic biology

Medicine by Design is not only a promising concept; it is also the name of an initiative at the University of Toronto (U of T) that aims to accelerate this new era of medicine. Medicine by Design is funding early-stage and translational projects in primarily regenerative medicine. It also sponsors post-doctoral fellowships and travel awards, offers communication-, career- and commercialization workshops, and much more. Importantly, the initiative also invests in synthetic biology. For example, it helped launch the Medicine by Design Synthetic Biology Discussion Group, which takes place once per month alongside the Single Cell, Organoid and Computational Discussion Group meetings. The Medicine by Design Synthetic Biology Discussion Group has more than 140 subscribers, including students, post-doctoral fellows and professors at U of T, as well as professionals from industry and government (Figure 2). The event offers a space to present work, discuss synthetic biology-related topics, start collaborations and, not to forget, enjoy Medicine by Design sponsored pizza. For more information, please see below the summary of past discussion group meetings. It gives a good overview of synthetic biology-related work that is currently happening at U of T.

Other efforts include bringing synthetic biology closer to high-school students with booths at the Regenerative Medicine Expo or financial support of the U of T’s iGEM team. Medicine by Design has also supported the hiring of several new faculty members with expertise in synthetic biology, including Prof. Keith Pardee in the Leslie Dan Faculty of Pharmacy (cell-free synthetic biology), and Prof. Leo Chou (DNA nanotechnology) and Prof. Michael Garton (mammalian synthetic biology) at the Institute of Biomaterials & Biomedical Engineering. Finally, Medicine  by Design is funding interdisciplinary projects that integrate the expertise of those new faculty and more senior synthetic biology faculty, including Prof. Krishna Mahadevan (Metabolic Systems Engineering).

A short summary of previous and future MbD Synthetic Biology Discussion Group meetings:

2018 

February 28th Dr. Benjamin Scott, former PhD student Belinda Chang lab, current postdoctoral associate at the National Institute of Standards and Technology (NIST) in Washington DC “Studies of Human GPCRs Using Yeast” & “The Goals of SynBio Canada”

March 27th Dr. Trevor McKee, Group leader at the Computational Pathology core facility at STARR “Moving from Images to Data: Resources and expertise in computational pathology at the STTARR core facility”

April 24th Dr. Brendan Hussey, former PhD student David McMillen lab, current postdoc “Programmable T7-based synthetic transcription factors”

June 26th Aaron Trotman-Grant (MSc Student Dana Philpott lab) & Laura Prochazka (Postdoc Peter Zandstra lab) “Trends in Mammalian Synbio: Take home massages from the 5th International Mammalian Synbio Conference”

July 31th Ashton Trotman-Grant, PhD student Juan Carlos Zuñika-Pflücker lab “Designing ‘Smart’ Immune Cells to Expand Therapeutic Capabilities”

August 28th Christian Euler, PhD student Krishna Mahadevan lab “Reverse and Forward Engineering: Modeling Real and Synthetic Systems”

October 30th Kaushik Raj, PhD student Krishna Mahadevan lab “Emergent properties in gene regulation”

Figure 3: Self-identification and interest in synthetic biology among the participants of the MbD Synthetic Biology Discussion Group

November 27th Dr. Keith Pardee, Assistant Professor at Leslie Dan Pharmacy Faculty “Rapid, Low-cost Tools for Human Health”

2019

March 26th Dr. Leo Chou, Assistant Professor Institute of Biomaterials and Biomedical Engineering (IBBME) “What can DNA nanotechnology do for synthetic biology”

April 30th Lyla El-Fayomi, MSc student Derek van der Kooy lab “Science at the Speed of Light: Optogenetics 101”

May 28th Dr. Michael Garton, Assistant Professor Institute of Biomaterials and Biomedical Engineering (IBBME) “Bringing protein interface design to the synthetic biology party”

July30th Jenise Chen (PhD Student Shana Kelley lab)“A multiplexed, electrochemical interface for cell-free synthetic toehold-mediated gene networks”

October 29th Dr. Michael Aregger (Postdoc Moffat lab) “Global mapping of human genetic interactions using CRISPR-Cas screens”

More Synthetic Biology at the University of Toronto

Medicine by Designs’ investment in synthetic biology has been great, but medicine is certainly not the only application where the field is going to make a difference. In fact, U of T  has been in the synthetic biology game long before Medicine by Design existed. For example, the centre for Applied Bioscience and Engineering (BioZone) at U of T was created to promote work at the interface of biology and engineering. BioZone is integrating expertise in computational modeling, genomics, enzyme-, metabolic- and process engineering with a focus on production of biofuels, bioremediation, wastewater treatment, and microbiome-related health applications. There is also the Synthetic Biology Innovation Cluster founded in 2013 by U of Ts’ Impact Centre, led by Prof. David McMillen and Stanley Wong. The cluster aims to connect industry and academics in Ontario and has hosted several successful summer programs to help train the next generation of synthetic biologists. Importantly, U of Ts’ innovative research in synthetic biology combined with Toronto’s start-up scene has already led to the creation of synbio startups including Phycus Biotechnologies, Spindle Biotech, and Ranomics.

U of T is also a leading institution in genomics, systems biology and artificial intelligence, which are areas that are certainly becoming more integrated with synthetic biology. Examples are the laboratories of Prof. Alán Aspuru-Guzik (AI, lab automation, material & drug discovery), Prof. Brendan Frey (AI, Systems Genomics) with company DeepGenomics, Prof. Charles Boone & Prof. Tim Hughes (functional genomics), and Prof. Jason Moffat (genome editing, systems biology). (and yes, the list could go on and on, so please forgive me for stopping here, missing many other excellent labs.)

Finally, U of T has a highly active and well organized iGEM team that has operated since 2007, and with every year the number of interested students and their success at the international iGEM competition increases. Last but not least, let’s not forget the numerous proactive U of T students who, despite the lack of formal synbio programs and, until now, sparse numbers of synbio laboratories, follow their passion and conduct synbio related projects in non-synbio labs, engage in the Medicine by Design discussion group meetings and help create a U of T and Canadian synthetic biology community (highlighting U of T alumni, Dr. Benjamin Scott who created synbiocanada.org).

Opportunity Biology by Design

With that I want to close, and hope that this post was somewhat useful, in particular for current and future students and postdocs at U of T who aim to pursue a career in synthetic biology, for those who feel a little lost in the giant U of T system and for those who are looking for a program and appropriate training in synthetic biology.  As a side note, the number of students in the latter category is probably larger than we think. This is supported by the fact that U of Ts’ iGEM team had more than 200 applicants last year, and by the number of students who indicated that they are interested in synthetic biology but don’t conduct work in the area on the synthetic biology discussion group survey (Figure 3).

Certainly, dedicated programs and funding are very much needed but until then, I believe, there are numerous ways to work in, transition to or engage in synthetic biology at U of T. In the end, synthetic biology is just a term. Synthetic biology is molecular biology, computational biology, systems biology, cell biology, genetics, engineering, creativity, design, ideas, dedication…. it is the learning of how to create biological devices and systems so we can make medicines by design, agriculture by design, food by design, remediation by design, energy by design. So we can make biology by design. So we can eventually make everything (well almost) of biology! Thus, regardless of your department, lab or program, you can always create your own “synbio mind” and sooner or later become part of the solutions that allow us to take care of our health and the environment. I am convinced there are plentiful ways to do that at U of T and at any other institution in Canada.

Thanks for reading and please feel free to drop some comments below or send me or info@synbiocanada.org a message.

Acknowledgements

I want to thank Dr. Benjamin Scott (President of SynbioCanda.org) and Ann Perry (Manager, Strategic Communications & Operations at Medicine by Design) for proofreading and editing. Medicine by Design supports me with a Medicine by Design postdoctoral fellow award and is funded in part by a $114-million award from the Canada First Research Excellence Fund (CRFEF). I am further supported by CIHR. Finally, I want to thank Prof. Dr. Peter Zandstra for continuous support and mentorship.

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.