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Marika Ziesack on Circe

The Humans of the Wyss (HOW) series features members of the Wyss community discussing their work, the influences that shape them as scientists, and their collaborations at the Wyss Institute and beyond. 

Marika Ziesack on Circe
Marika Ziesack, Research Scientist. Credit: Wyss Institute at Harvard University

It’s been more than 20 years since Marika Ziesack’s first Taekwon-Do class, and now she says it has become a lifestyle to her. As with all martial arts, attention to detail and perseverance are two of the keys to success. She believes these same skills are directly applicable to her career as a scientist. Attention to detail is vital when performing and analyzing experiments. Perseverance has been essential as Marika has grown at the Wyss from a Ph.D. candidate to a Research Scientist co-leading her own project. Now, Marika is working to spin out Circe, a system that uses microbes to turn greenhouse gases into specific polymers with applications in bioplastics and dairy alternatives. Learn more about Marika and her work in this month’s Humans of the Wyss.

What are you working on?

I am co-leading the Circe project with Shannon Nangle. Circe is a system that uses microbes to turn greenhouse gases into tailored polymers with applications in packaging, personal care products, and dairy alternatives. The system consists of three parts: a CO2 point source, a fermentation system, and a downstream processing unit. The CO2 point source can be any manufacturing facility that emits CO2, from a small craft brewery to a power plant. We would co-locate with them and take their CO2, producing the other feedstock gas (hydrogen) on site using water electrolysis, a process that breaks down water using the passage of an electric current. These gases are then fed into our fermentation system, which is where we have the actual vessel for fermentation. That’s where the microbes are cultured and the tailored polymers are developed. Finally, once the microbes have produced what we want, they go to a downstream processing unit where we take out the product and prepare it to be sold as ingredients for different kinds of industries.

Marika Ziesack on Circe
The Circe process begins with a CO2 point source, moves to a fermentation system, and ends at a downstream processing unit. Credit: Wyss Institute at Harvard University

The first product classes that the Circe system will produce are PHAs (polyhydroxyalkanoates) which are bioplastics, and TAGs (triacylglycerols) which can replace milk fats. PHAs have applications in packaging, textiles, and as personal care ingredients. Our materials are completely biodegradable, so if they ended up in the ocean or in terrestrial environments, they’d just be eaten up by microbes, unlike the polluting petrochemicals currently used to make these materials. With PHAs, we have accomplished a proof of concept, we’ve made some tailored polymers, and we’re in the process of scaling up. We started with a 100mL lab scale production and now we’re working on a 4L actual fermentation system.

More recently, we’ve started looking into the food sector where we could use TAGs to make milk fat replacements. Surprisingly, the biology of these two products is very similar. We’re able to use our genetic engineering knowledge and the tools we’ve developed to produce milk fats that directly mimic what a cow does, just without the cow. This means our carbon footprint is lower, we need less water, and we won’t rely on industrial farming. If you’ve ever had vegan cheese, you probably know how awful it is. We’re hoping to bring the taste and texture back into plant-based cheeses and butters. This product class is still in the proof-of-concept stage.

What real-world problem does Circe solve?

Marika Ziesack on Circe
Using microbes that feed on greenhouse gases, Circe would make the manufacturing process more sustainable. Credit: Wyss Institute at Harvard University

We see Circe as once piece of the puzzle towards a circular and more environmentally friendly manufacturing industry. Right now, most manufacturing processes emit CO2 as waste. While it doesn’t really cost those industries anything, it definitely costs the environment and our future. We want to end the notion that CO2 is a waste and start using it as a resource.  A key aspect of Circe is that we employ microbes to turn simple and abundant feedstock into complex chemicals. From our research we have developed the knowledge and tools to be able to direct these microbes into producing materials with desirable properties. Our vision is for the Circe process to integrate with existing manufacturing processes to help them emit less CO2, use their resources more efficiently, and give them an economic advantage.

Most manufacturing processes emit CO2 as waste. While it doesn’t really cost those industries anything, it definitely costs the environment and our future. We want to end the notion that CO2 is a waste and start using it as a resource.

Marika Ziesack

Circe is an Institute Project. How has that helped you towards your translation goals?

Marika Ziesack on Circe
Marika Ziesack (right) and the other co-leader of the Circe project, Shannon Nangle (left). Credit: Wyss Institute at Harvard University

The experience with the Institute Project has been awesome. Before we knew about the Institute Project, Shannon and I had been thinking about how to bring this technology to market for a few months. We had spoken to a couple of investors and even accelerator programs. We consulted with other startups to help develop our business model. As our postdocs came to an end, we had to figure out our next step, and that’s when we learned about the Institute Project. It was perfect! It was exactly what we needed. The Institute Project program aims to take technology developed in the lab and prepare it for commercialization. We got help responding to customer and investor feedback that we collected. Based on that, we set and are working to complete technical and business milestones to prepare for seed funding.

Our technical milestones involve prototyping, building predictive techno-economic models, and constructing a lab-scale gas fermentation system. We are sending materials out to potential customers to allow them to try our materials in their processes and products in return for their feedback, which will be very useful. We’re also building a techno-economic model, which is basically a financial projection that also strongly considers the technical aspects. We’ve been building out the fermentation system and demonstrating scale-up. The addition of the TAGs as a second target product class was another milestone. These are exactly the things that we need in order to go back to investors and say, “Hey, we’re ready.”

These are exactly the things that we need in order to go back to investors and say, ‘Hey, we’re ready.’

Marika Ziesack

We have a lot of support from other parts of the Wyss Institute. Jessica McDonough from Business Development helps us make connections and counterchecks our ideas. Jim Niemi and Hani Sallum from the Advanced Technology Team have been a big help with our fermentation system, given the collective experience in product development they bring from working in industry. It’s not just the monetary support we value, it’s also being able to grow and continue to develop our idea in an environment we’re familiar with that’s especially designed for this type of technology translation.

What inspired you to get into this field?

Marika Ziesack on Circe
Marika Ziesack and her iGEM team from Heidelberg in 2008. Credit: Marika Ziesack

One thing that really started my path towards synthetic biology and engineering microbes was the iGEM (International Genetically Engineered Machine) competition. iGEM is a competition where students around the world work in teams to address different challenges using synthetic biology. In my second year of college, I was part of the iGEM team in Heidelberg, Germany. The program culminates in a large event, which was the first time I came to the United States. Everyone was super excited about their science. People were more daring and there were new types of innovations that I’d never seen in Germany. When I saw all of that, I decided I definitely wanted to come here to do my Ph.D. iGEM also made me realize how much potential microbes have to become useful tools for society. They can live everywhere. They can do all kinds of chemical reactions and they are simple enough that we can understand and modify them.

Since I always liked nature and animals, I wanted to apply bacteria to preserve the environment, which led me to Wyss Core Faculty member Pam Silver’s lab for my Ph.D. Towards the end of my Ph.D. thesis Shannon joined the lab, and the rest is history.

What continues to motivate and excite you?

The vision keeps me motivated in a macro sense. I think the Circe system has the potential to fundamentally change how we do manufacturing, which would have a huge positive impact. I believe that Circe is part of a fundamental change to industry that includes many approaches to build a more sustainable and circular economy with cleaner manufacturing. That’s a future I am happy to be working towards. On a daily basis, I just enjoy doing lab work. I just love being in the lab. It’s a combination of the big vision and enjoying the small successes on a daily basis.

What are some of the challenges that you face?

I think the biggest challenge is juggling lab work and business development. I want to stay up to date and be sure I’m making enough progress. Sometimes I worry that I’m missing something because so much needs to be done. I need to be meticulous in how I manage my time. In the end, I think this motivates me to be rigorous on both sides and continue learning.

How have your previous experiences shaped your approach to your work today?

Marika Ziesack on Circe
Marika examining microbes during her Ph.D., a time when she learned a lot that still influences her work today. Credit: Wyss Institute at Harvard University

I learned a lot during my Ph.D. that has shaped my approach today. I was on a DARPA project and those government agencies have strict milestones, so I got used to following specific timelines. That’s how I learned important organizational and planning skills. When you’re starting a company, you need to be thinking in that way. You have to be on target. There’s only so much money and time.

Back then, getting things synthesized was pretty expensive and not so prevalent. There was a lot of DNA cloning involved in what I was doing, and I had to do everything myself. Having gone through that, I realize how long it takes and how inefficient it is. Now that there are less expensive and more reliable services, I’ve learned to outsource certain processes in order to make myself more efficient.

During my Ph.D. work, I did fundamental work on biofuels, so I was very aware of what was going on in that space. I observed multiple companies start out as biofuel companies and pivot to producing flavors and fragrances because there was more of a market for those products. I realized that a lot of these companies used a technology push rather than a market pull approach, so that is what we’re trying to avoid for Circe. It’s important to produce what the market wants.

When not in the lab, and not social distancing, how do you like to spend your time?

Marika Ziesack on Circe
Marika has been doing Taekwon-Do for more than twenty years. At this point, she sees it as a lifestyle. Credit: Marika Ziesack

I need to be active, that’s the way I reset. Taekwon-Do is the best way for me to do that. My mother signed me up for a class when I was nine years old and I’ve been practicing ever since. I’ve still been able to keep it up during the pandemic by converting my balcony into a gym with some equipment and a target. The group that I am part of has Zoom classes, and I set my own goals. It’s different than practicing with someone else, but I am hoping to come back stronger in some aspects than I was before.

I see a lot of similarities between doing Taekwon-Do and being a scientist. With both, no matter how long you do it, there’s always more to learn and ways you can improve. Another parallel is that as in any martial art, it’s all about being detailed in your technique and practicing with perseverance. If you mind the details and practice skills over and over, you’ll succeed and win a tournament or pass your belt test. In science, you have to mind the details and bringing a project to completion can take a long time and requires persistence.

In any martial art, it’s all about being detailed in your technique and practicing with perseverance. If you mind the details and practice skills, you’ll succeed. In science, you have to mind the details and bringing a project to completion can take a long time and requires persistence.

Marika Ziesack

Other ways I stay active are running, rock climbing, and biking. I love to read science fiction and fantasy books. I also have a guitar. I’m not an artist, but singing is how I learned most of my English pronunciation. 

If you had to choose an entirely different career path, what would it be?

I would have either been a stunt woman or a veterinarian at a zoo, since those were the other two career paths I thought about before choosing to be a scientist. When I was in high school, I had a motorcycle and I did two different types of martial arts, Wing Chun and, of course, Taekwon-Do. There was a program in Munich where you could study stunt mechanics, and I looked into it, but it involved a lot of physics and I didn’t like physics as much back then. My dad was a vet, and I always liked all things nature, so going into veterinary medicine was definitely something I considered. But, at some point during high school I got to do an internship at a university lab and I just fell in love with science.

What does it feel like to be working on cutting-edge technology that has the potential to have a real and significant impact on people’s lives and society?

I’m doing exactly what I wanted to do; I feel like I am contributing to progress. I feel extremely lucky and privileged to be able to do this, and I’m thankful to all the people in my life that have supported me to get to this point. I’m going to do the best I can to actually make a positive impact on society.

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