Retooling microbes to upcycle CO2

Artwork ©Jennifer Sunami

By Lindsey Doermann

The U.S. Department of Energy has awarded a 5-year, $15 million grant to an interdisciplinary, UW-led team of synthetic biologists to engineer microbial genomes that transform CO2 into high-value chemicals. The project, led by chemical engineering professor James Carothers, brings together expertise in CRISPR gene-expression programs, single-cell RNA sequencing, data-driven design, and carbon-conserving pathway engineering. Its aim is to advance fundamental research into large-scale, bio-based chemical production that is not only greener, but also produces better alternatives to petrochemical-based products.

“This funding supports a high-risk, high-reward program to engineer different microbes to convert CO2 into chemicals,” says Carothers, who is also co-director of UW’s Center for Synthetic Biology and a MolES faculty member. “It will allow a bunch of people who’ve been working on different pieces of the challenge to pull in the same direction for a significant period of time.”

About 15 percent of every barrel of oil goes into making plastics and other ubiquitous products. That means we need new ways to make important products in order to fully give up fossil fuels. Bioproduction holds exciting potential for upcycling materials such as agricultural waste and captured atmospheric CO2 into precursors to plastics and more. The new paradigm could achieve an impressive trifecta of displacing petroleum, sequestering carbon, and making higher-performing products.

Over the past several years, the labs of Carothers and UW chemistry professor Jesse Zalatan have been pioneering CRISPR techniques to control gene expression in cells. So far, they can successfully introduce CRISPR gene expression programs that control 6-7 genes in a cell and direct it to perform different processes. For their current undertaking, however, they figure they’ll need to control at least 25 genes to effectively hack the carbon metabolism of microbes.

With pathway design experts such as Pamela Peralta-Yahya of Georgia Tech, they will explore how to engineer microbes to use all of its CO2 feedstock, as well as convert that carbon into high-value material. Carbon-metabolizing microbes in the wild can waste up to one-third of the carbon they intake as CO2, and the researchers believe they can improve that efficiency in their DNA redesign.

Rewiring cells so extensively is not only far more difficult, but the results can be unpredictable. That’s where new technology for sequencing RNA in a single cell comes in. Co-PIs Georg Seelig of UW’s electrical and computer engineering department and Anna Kuchina of the Institute for Systems Biology will apply this sequencing technique to decode if their re-programmed cells are behaving as intended. “This is an enabling technology that we didn’t really have before,” says Carothers, and it will allow his team to increase the number of programs they both build and test.

Additional machine learning, analysis and modeling expertise from researchers at two national labs and Herbert Sauro’s group in UW’s Department of Bioengineering will allow the team to design, build, test, and learn from a large number of iterations. That scale-up in the number of DNA programs to be investigated is crucial to developing fundamental principles, new tools, and design parameters for CRISPR-regulated genomes in all sorts of microbes.

With this concerted effort on basic research, the next generation of bioproduction — carbon-conserving and versatile — doesn’t have to be relegated to the distant future. “Even things that seemed like science fiction 10 or 15 years ago are realistic today,” Carothers says.

This project is funded through the Biological and Environmental Research program in the U.S. Department of Energy, as part of a $99.7 million investment in microbial biosystems design for the production of biofuels, bioproducts, and biomaterials. The grant includes PIs from the UW departments of chemical engineering, chemistry, bioengineering, and electrical and computer engineering; Pacific Northwest National Laboratory; Lawrence Berkeley National Laboratory; Institute for Systems Biology; and Georgia Institute of Technology.

Unlocking biotechnology with RNA

Jason Fontana (left) and David Sparkman-Yager (right) began working together as molecular engineering graduate students in chemical engineering professor James Carothers’ lab. Photo by Dennis Wise / UW Photography

Imagine if there were drugs that could optimize their dose in real-time, leading to better patient outcomes. Cellular factories that could self-regulate their metabolism, enabling sustainable chemical production. Gene editing tools that could target specific cells, reducing toxic off-target effects. The key to realizing those technological advances, according to University of Washington molecular engineering alums Jason Fontana and David Sparkman-Yager, is RNA.

RNA is a molecule with many functions in the cell, from coding proteins to catalyzing chemical reactions. One type of RNA molecule, called an aptamer, detects molecules with high affinity and specificity, similar to how an antibody binds an antigen. In nature, cells use RNA aptamers like sensors to monitor their environment and respond in real time; for example, they can modulate gene expression as a result of changes in the local concentration of small effector molecules.

If scientists could dictate which molecules RNA aptamers bind to, and how the cell responds, they could engineer biology to solve complex problems.

Fontana and Sparkman-Yager have developed a computational platform that allows them to do just that. Their technology is based on research they conducted for their theses under chemical engineering professor James Carothers, and chemistry professor Jesse Zalatan. In January 2021, they started a company, Wayfinder Biosciences, to apply this platform to everything from sustainable biomanufacturing to targeted therapeutics.

“We’ve figured out how to design RNA so that we can control how biology responds, on demand, to the molecules we choose,” said Fontana, who received his Ph.D. in molecular engineering in 2020. “Basically, we pair RNA aptamers with another piece of RNA that does something useful, such as producing a measurable output like light or activating a guide RNA to induce gene editing, only when the aptamer binds its target.”

Wayfinder Biosciences engineers smarter RNAs, controlling where, when and how RNA functions. Image courtesy of Jason Fontana.

“By elucidating the quantitative design rules governing how RNA folds and functions, we can identify aptamer-based switches that are likely to work before even going into the lab,” said Sparkman-Yager, who also received his Ph.D. in molecular engineering in 2020. “This process is much faster and easier than screening thousands of candidates from a large random sequence pool.”

Among the many different applications for this technology, one area Fontana and Sparkman-Yager are currently pursuing is biomanufacturing. Many molecules are colorless and hard to measure, requiring cumbersome and slow analytical methods to quantify. Using their platform, Fontana and Sparkman-Yager can design RNA that emits an easily-measured fluorescent signal upon detecting (and binding to) a specific molecule, effectively allowing the RNA to indirectly measure the concentration of the molecule of interest. The team is engineering such RNA sensors to measure the amount of Human Milk Oligosaccharides (HMOs) – the main component of human milk that is missing from the cow’s milk used in infant formula – within complex mixtures, accelerating biomanufacturing efforts.

Another application Fontana and Sparkman-Yager are particularly excited about is CRISPR. CRISPR-based therapies use what’s known as guide RNAs to direct DNA cutting enzymes to remove and repair specific sequences of DNA in the cell. These therapies have come a long way since CRISPR was first used to edit genes in mammalian cells in 2013, but are still hindered by low specificity and off-target effects. The Wayfinder team is working on developing RNA sensors that can turn CRISPR on and off in response to changes in the local environment.

“By combining RNA aptamers with CRISPR guide RNAs we will be able to target CRISPR such that gene editing is only activated when and where it is needed,” said Sparkman-Yager. “This will help make CRISPR safer and more cost effective.”

Starting a startup

“We’re scientists, not business people,” said Fontana. “We knew that we would need help launching a company. Luckily, there are many resources on campus that we could take advantage of.”

In the spring of 2020, Fontana and Sparkman-Yager participated in the I-Corps program at CoMotion. Funded by the National Science Foundation, the program aims to “accelerate academic research projects that are ready to move toward commercialization.”

“The I-Corps program helped us test the viability of our idea by pushing us to talk to potential customers and figure out if the tech we are developing is something that they actually need or want,” said Fontana. “This was a really great starting point because the stakes were pretty low. As students exploring a business idea, we found that people were very willing to talk with us and give us honest feedback.”

Added Sparkman-Yager, “Our experience in the I-Corps program crystallized for us that there is a market for our technology and that there are real-world problems that we can use our technology to solve. That was a big moment for us.”

The team subsequently applied for and received a grant from the Innovation Gap Fund in fall 2020. A partnership between CoMotion and the Washington Research Foundation, the Innovation Gap Fund awards grants to novel projects with promising impact, helping university innovators transition from academic research grants to attracting seed-stage investment. In addition to $50,000 in funds, the program provided the team access to business, IP and technical experts to guide them as they began officially forming their company.

Said Fontana, “Thanks to these UW programs, we not only met some of our current investors and advisors, but we were also able and prepared to pursue other opportunities beyond campus.”

For example, Fontana used part of the $2,500 he received from I-Corps to attend the 2021 Built with Biology conference which brings together investors, engineers, entrepreneurs and others in the synthetic biology community. At the conference, he met someone from IndieBio – an accelerator based in San Francisco that supports early-stage biotechnology companies – and quickly landed a coveted spot in their 12th cohort of startups.

“It’s a big adjustment to go from conducting research in the lab as a scientist to coming up with a business strategy and meeting with potential investors as a founder,” said Fontana. “IndieBio was like an accelerated bootcamp for science entrepreneurs, teaching us how to successfully raise a seed round so that our company can grow, expanding our network through countless introductions and giving us lab space to continue our research.”

Last year, the Wayfinder team was also selected to be part of the first ever Seattle cohort of the Creative Destruction Lab (CDL). CDL is a nonprofit organization that runs startup accelerators around the world. In 2021 they launched an accelerator in Seattle, based at the UW’s Foster School of Business, for early-stage, science-based technology companies. CDL has a unique format: companies are selected to participate in a series of meetings where company founders pitch CDL mentors in the hopes that they will agree to mentor their company for the duration of the program. If no one volunteers to mentor the company, the company founders are not invited back to the next meeting.

“The CDL program sometimes felt like a game show!” said Sparkman-Yager. “It’s been a challenging but really awesome experience. We’ve met lots of people from the Seattle tech and investing communities, who as mentors, have helped us think about how we can use our technology to change the world in meaningful ways.”

Student entrepreneurship

Neither Fontana nor Sparkman-Yager set out to be entrepreneurs when they began pursuing their Ph.D.s, but both jumped at the chance to commercialize their RNA aptamer technology.

“To this day, I am in awe of RNA and excited about programming it to carry out novel functions,” said Sparkman-Yager. “As a graduate student, I spent so much time diving deep on this topic that the idea of graduating and moving on to something else felt like a missed opportunity. In starting a company, not only do I get to continue pursuing this work, but I get to hopefully see it reach its full potential.”

Fontana and Sparkman-Yager attribute the flexibility of the molecular engineering program and the support of their Ph.D. advisors as integral to the development of Wayfinder’s technology.

“As a MolE student I was able to take courses based on what I wanted to learn, not what discipline they were technically tied to, accelerating my research,” said Sparkman-Yager. “I also benefited from James’ mentorship as he allowed me to take on a big research question that no one had an answer for which ultimately led to Wayfinder.”

When asked what advice they have for students interested in becoming entrepreneurs, both Fontana and Sparkman-Yager agreed: don’t do it alone.

“Know your strengths and weaknesses and find people who complement them,” said Fontana. “This will help you to be competent as an entrepreneur, despite not having extensive experience.”

Said Sparkman-Yager, “Don’t become an entrepreneur just to be an entrepreneur. To be successful as an entrepreneur, you must be passionate about the technology. People can tell when you’re pitching something you don’t fully believe in. In my opinion, the right time to become an entrepreneur is when you see science that is not being utilized to its fullest potential and you think you know how to do that.”

When it comes to what you should do: take advantage of the resources UW gives you because there are many.

“In addition to the various programs and competitions available to innovators on campus, there is a thriving startup community to tap into,” said Fontana. “We’ve been fortunate to be able to learn from other synthetic biology startups that have emerged from the UW in recent years, such as A-Alpha Bio and Parse Biosciences. The UW is truly a great place to be an innovator.”

The future is RNA

The Wayfinder team in the lab. Courtesy of Jason Fontana.

Thus far, Fontana and Sparkman-Yager have raised over $1.1 million and are currently in the midst of raising a highly sought-after seed round. In February, the Wayfinder team moved into CoMotion’s incubator space in Fluke Hall. They are focused on building out their team – hiring a lab manager, research technicians and scientists with expertise in relevant areas – with the goal of getting their research capabilities up and running as quickly as possible.

“The Fluke Hall incubator space is not only cost effective, but great for recruiting students and staying connected to the UW community,” said Sparkman-Yager. “Moreover, we’re excited to be neighbors with A-Alpha Bio which also has lab space in Fluke.” “This technology has so many potential applications, allowing us to tap into, and hopefully help solve, all sorts of challenging problems,” said Fontana. “We’re looking forward to seeing what the future holds for biotechnology.”

UW BIOFAB: A force for reproducible science

The UW’s Biofabrication Center partners with Agilent Technologies in pursuit of automated, reproducible research

Undergraduate technicians perform common molecular biology tasks to enable the rapid design, construction and testing of genetically reprogrammed organisms for biotechnology applications and research. Dennis Wise / University of Washington

Key to advancing any new scientific discovery is the ability for researchers to independently repeat the experiments that led to it. In science today, particularly biology, the lack of reproducibility between experiments is a major problem that slows scientific progress, wastes resources and time, and erodes the public’s trust in scientific research.

At the University of Washington, researchers have access to the UW Biofabrication Center, or BIOFAB, a unique facility located in the Nanoengineering and Sciences building in which scientific protocols are encoded as computer programs, allowing undergraduate lab technicians to execute experiments according to detailed instructions.

“The BIOFAB is unlike any other lab on campus,” says BIOFAB founder Eric Klavins, Professor and Chair of the UW Electrical and Computer Engineering Department. “In effect, we’ve been able to automate common protocols by using software to assist our student technicians. This ‘human-in-the-loop’ system goes a long way towards improving the replicability of biological research.”

In an effort to expand the lab’s automation capabilities, the BIOFAB has partnered with Agilent Technologies Inc., a life sciences development and manufacturing company based in California’s Silicon Valley. Using state-of-the-art research equipment from Agilent, the BIOFAB will develop high-throughput workflows for common tasks of interest to members of the synthetic biology community.

Programming the biology lab

Computer programmers write code to tell a computer what to do and how to do it. For a given program, the same inputs consistently result in the same outputs.

In contrast, two biology researchers can seemingly carry out the same experiment, but get different results. This is in part because instructions for how the experiment was conducted – whether documented in a lab notebook or published in a journal – are often vague or incomplete, leaving out details that the author may not have realized impacted the experimental outcome.

Aquarium is a web-based software application that allows scientists to build executable protocols, design experimental workflows based on those protocols, manage the execution of protocols in the lab and automatically record the resulting data. Dennis Wise / University of Washington

As a computer scientist turned synthetic biologist, Klavins realized what biologists needed was a more formal way – a programming language – to define how to conduct an experiment. This led to the development of Aquarium, a web-based software application that allows scientists to build executable protocols, design experimental workflows based on those protocols, manage the execution of protocols in the lab and automatically record the resulting data.

“Aquarium provides the means to specify, as precisely as possible, how to obtain a result,” said Klavins.

When it comes to engineering biology – reprogramming cells to produce chemicals or drugs, or perform complex functions like sensing toxic compounds in the environment – reproducibility is paramount. The BIOFAB uses Aquarium to standardize various scientific workflows, generating reliable and highly reproducible results. The BIOFAB is one of a growing number of labs known as biofoundries which are committed to efficiently engineering biological systems and workflows.

BIOFAB operations are overseen by two lab managers, with a dozen or so undergraduate students executing jobs for BIOFAB clients. BIOFAB technicians perform common molecular biology tasks like DNA assembly and purification as a fee-for-service to the scientific community. Since its founding in 2014, the BIOFAB has run over 30,000 jobs for 300+ different clients at the UW and beyond.

“The BIOFAB has been absolutely instrumental in establishing and executing robust Aquarium driven protocols for a major portion of our de novo design minibinder pipeline,” said Lance Stewart, Chief Strategy and Operations Officer at the UW’s Institute for Protein Design (IPD). IPD researchers use computers to design millions of minibinders – small, stable proteins that bind with high affinity to targets of interest – that must be produced and tested in the lab. IPD uses the BIOFAB to screen minibinder candidates for protein stability and protein:protein interactions, which involves constructing yeast libraries from chip synthesized oligonucleotide genes encoding minibinder designs and carrying out large scale fluorescence activated cell sorting and next generation DNA sequencing.

“By handing off time-consuming wet lab work to our technicians, BIOFAB clients like IPD can focus more on the design and data analysis aspects of their experiments,” said Klavins.

Learning by doing

On any given day, the BIOFAB is buzzing with undergraduate technicians working together in harmony to complete an assortment of experiments for BIOFAB clients. Most technicians start working in the BIOFAB as freshman or sophomores, and for many, it’s their first real lab experience.

BIOFAB technician Nicole Roullier. Dennis Wise / University of Washington

Upon joining the lab, BIOFAB lab managers teach students basic lab skills, such as pipetting and sterile technique, and orient them to the lab. Armed with this foundational knowledge, BIOFAB technicians can begin executing a variety of different protocols by following the step-by-step instructions provided through Aquarium. Students become adept at performing complicated experimental workflows involving complex equipment through the process of doing them over and over again.

“Aquarium allows us to effectively train many students simultaneously and get them working in the lab relatively quickly,” said Aza Allen, a lab manager at the BIOFAB. “Aquarium’s technician interface makes it easy to get undergraduate students, who do not necessarily know much about molecular biology when they start, to perform experiments reliably.”

“I have learned so much beyond what could possibly be taught in a classroom setting,” said BIOFAB technician Nicole Roullier, a UW biochemistry senior. “Most undergraduates don’t have the opportunity to work with such sophisticated equipment and master advanced techniques like qPCR and next-generation sequencing (NGS). This hands-on training has built up my confidence in the lab in preparation for graduate school.”

A promising partnership

The BIOFAB provides critical automation and analytics infrastructure dedicated to enabling the rapid design, construction and testing of genetically reprogrammed organisms for biotechnology applications and research. Through its partnership with Agilent, the BIOFAB aims to offer new high-throughput capabilities that will further speed up and scale up synthetic biology research.

“We’re thrilled to be partnering with Agilent,” said Klavins. “Their support will not only accelerate the development of innovative technologies, but will help us educate students using cutting-edge equipment, bolstering our ability to prepare students for success in their own future research and career.”

“We think this is the start of an exciting collaboration,” said Kevin Meldrum, General Manager and Vice President of Genomics at Agilent. “We are pleased to be able to support researchers at the UW and the educational mission of the university through the BIOFAB. We see this as an investment in the future of our field.”

Agilent’s state-of-the-art liquid-handling robot, the Bravo Automated Liquid Handling platform will help speed up and scale up synthetic biology research. Dennis Wise / University of Washington

As a result of this partnership, the BIOFAB has acquired several valuable pieces of equipment, including Agilent’s state-of-the-art liquid-handling robot, the Bravo Automated Liquid Handling platform. While the Bravo can be used to automate sample preparation for a variety of different applications, the BIOFAB plans to initially use it to expedite its workflow for NGS. In addition to the Bravo, the BIOFAB has also acquired the AriaMx Real-Time PCR System, and the 5200 Fragment Analyzer System, a parallel capillary electrophoresis system.  

“Library preparation for high-throughput NGS is a tedious, labor-intensive process,” said Klavins. “Agilent’s Bravo will help make this workflow more efficient and reduce pipetting errors that make results less consistent, while also freeing up time for our technicians to work on less repetitive tasks. We know that there are certainly other workflows that would benefit from the use of Bravo, and we plan to engage BIOFAB users to identify which ones to pursue. We are thrilled to be able to bring this resource to the UW community, and are excited to see the compelling science that comes out as a result.”

UW synthetic biologist James Carothers wins ARPA-E award to develop new CO2 bioconversion process

An interdisciplinary research team led by University of Washington chemical engineering associate professor James Carothers received $1.7 million in funding from the U.S. Department of Energy’s Advanced Research Projects Agency-Energy (ARPA-E). The funding will be used to develop scalable, cell-free platforms that enable the capture and conversion of carbon dioxide (CO2) into industrial chemicals, providing manufacturers with a cheaper, more efficient and sustainable means of chemical production.

James Carothers
James Carothers

“Cell-free systems have the potential to revolutionize biomanufacturing; however, it has been challenging to integrate the large number of disparate functionalities required for complex processes,” said Carothers, who is also member faculty at the UW’s Molecular Engineering & Sciences Institute and the Center for Synthetic Biology. “We are developing technologies that could be used to assemble novel biocatalytic pathways, paving the way for the robust transformation of greenhouse gases like CO2 to desirable chemical products.”

Building a functional multi-enzyme system from the bottom up requires a vast array of expertise. The team includes Dr. Alex Beliaev, a microbial physiology expert and senior staff scientist at the Pacific Northwest National Laboratory, professor Neha Kamat, membrane-based biomaterials expert at Northwestern University, professor Vincent Noireaux, a pioneer of cell-free transcription-translation systems at the University of Minnesota, and Georgia Tech professor Pamela Peralta-Yahya, a metabolic engineer specializing in the production of advanced biofuels and commodity chemicals.

Carothers received this competitive award from ARPA-E’s Energy and Carbon Optimized Synthesis for the Bioeconomy (ECOSynBio) program, which focuses on developing advanced synthetic biology tools to engineer novel biomass conversion platforms and systems that are more efficient and produce less emissions than current fermentation processes widely used in biorefining.

The team’s initial goal is to develop a cell-free system to convert CO2 into malic acid. Malic acid can be made into a variety of chemicals, including maleic anhydride which had a 2018 market size of $2.77 billion and is used to make everything from plastics for cars and boats, to water treatment detergents, insecticides and fungicides, and pharmaceuticals. Malic acid – like most commodity chemicals – is made using fossil fuels, generating significant CO2 emissions in the process. Despite the urgent need to reduce our reliance on fossil fuels, alternative approaches have not yet been adopted due to lack of scalability and cost.

Instead of going through the inefficient and costly process of independently producing and purifying every enzyme needed to convert CO2 to malic acid, the team will use the cell’s own machinery – in the form of cell lysates – to synthesize scalable quantities of enzymes from DNA templates in a reaction mixture outside of the cell. To further optimize the bioconversion of CO2, researchers will engineer technologies to control the timing and expression level of different enzymes. This cell-free system will also include a biosynthetic module that regenerates cofactors – non-protein chemical compounds required for an enzyme’s catalytic activity – reducing the need for expensive cofactor supplements.

“Our platform will not only slash CO2 emissions compared to petroleum-based maleic anhydride production, but will actually sequester one ton of CO2 for each ton of product that it makes,” said Carothers. “The potential greenhouse gas savings here are significant.”

By enabling the industrial-scale, carbon-negative synthesis of high-value chemicals, this promising platform could help make a robust and sustainable bioeconomy a reality.

Read the full press release from DOE here.

How to build a network of pharmaceutical biofactories

By Lindsey Doermann | Originally published on the UW Chemical Engineering website

Advances in synthetic biology and biomaterials open up exciting prospects for distributed manufacturing of drugs, food products, and other commodities

illustration of pills filled with network pattern

During the world wars, American factories that ordinarily made cars and appliances changed up their production lines to manufacture guns, tanks, and aircraft in support of the war effort.

Fast forward to today when we’re facing a different fight, the adversary being a novel virus. When a disease spreads, certain drugs and their precursors can suddenly become as valuable as tanks and body armor. Is there a way re-tool pharmaceutical manufacturing, as industries did during the war, to help meet demand for valuable molecules? 

An interdisciplinary research team that includes UW engineers thinks so — by employing a synthetic-biology take on wartime manufacturing. Their goal is to design flexible, plug-and-play modules that produce valuable products within existing fermentation equipment. Put another way, breweries, distilleries, and other fermentation facilities could adapt their “peacetime” operations to start churning out pharmaceuticals in response to public health emergencies.

The group is led by soft-materials specialists Lilo Pozzo of ChemE and Alshakim Nelson of Chemistry; synthetic-biology experts James Carothers of ChemE and Hal Alper of University of Texas, and small-scale automation expert Nadya Peek of HCDE. The team recently received NSF funding to develop the technology and prototype modules for distributed chemical manufacturing. Here’s how it would work.

Many of our drugs or drug precursors derive from plants. Aspirin originally came from tree bark, opiates have been farmed from poppy flowers, and the anti-cancer agent Taxol was derived from the bark of the Pacific Yew tree. The anti-malarial artemisinin is still largely sourced from the leaves of sweet wormwood trees farmed in Asia and Africa.

But when it comes to pharmaceutical production, Pozzo points out, “plants are inefficient because the component you want to isolate may exist in very, very small quantities.” Thanks to synthetic biology (SynBio), researchers can hack this process by genetically modifying bacteria and yeast cells to overproduce desired chemicals. Think of it as a sophisticated form of brewing beer.

3d printed hydrogel lattice
A 3D-printed hydrogel lattice. Photo courtesy of Trevor Johnston/Nelson Lab.

In a February Nature Communications paper, Nelson and Alper reported a major step toward making SynBio systems portable and adaptable. They discovered how to embed genetically-modified microbial “factories” within a 3D printed hydrogel. In this configuration, they can constrain chemical production to within the gel (as opposed to dispersed in a large fermenter), run reactions continuously, and even grow more than one microbe within a bioreactor.

Now, chemical engineers can help move the ball further. In the new project, the ChemE’s will focus on developing new materials that optimize the transport of both the nutrients into the system and the chemical product out. Extracting the end product efficiently has long plagued this technology. But now, with the hydrogel framework and chemical engineers at the ready to solve some transport problems, it has new potential.

In parallel with the ChemE work, HCDE’s Nadya Peek will take the lead on designing the human-centered automation workflows for the modules. “You have to think about the human aspect of this,” says Pozzo. “Users may not have the same levels of expertise.” To be successful, the team needs to create a system that’s plug-and-play, works within existing infrastructure, and doesn’t require PhD-level training to operate.

The multifaceted project offers exciting opportunities for students, as well. Pozzo is developing design projects for ChemE undergraduates that look at the economics of different products that could be made by the SynBio systems. Students could consider not only chemical production aspects — e.g. how hard is it to make a given molecule? what are the yields using current methods? — but also the demand and market forces. The researchers view the modules as a flexible platform, and Pozzo thinks the students can help reveal just how flexible it can be.

In fact, she thinks the pharmaceutical materials are only the beginning. If you can make plant-derived drugs this way, why not other plant or even animal-based products? In the burgeoning field of cellular agriculture, microbial “factories” can replace some traditional farming operations to produce our food. In farming, animals serve as rather inefficient bioreactors to produce meat, milk, and eggs. But cells in SynBio systems are capable of producing the same things in a climate-friendlier manner, bypassing animals altogether.

Factories are traditionally designed to make one product. Reconfiguring an auto plant to produce ventilators, however critical, is a big undertaking. But think: if your factory is a cell, then reconfigurations occur on the micro scale. “You wouldn’t need to have large-scale manufacturing if you could design a cartridge, for example, that you could plug into existing fermentation equipment,” says Pozzo.

Breweries, distilleries, and commodity chemical producers exist all over the country. What if they became a network of “farms” for food or pharmaceutical products that can adapt to emergency shortages? What if microbial factories could supply some of the food we eat every day? It turns out that a big idea for a new way of manufacturing may actually be microscopic.

This work is funded through the National Science Foundation’s Emerging Frontiers in Research and Innovation (EFRI) program, which invests in high-risk, high-reward multidisciplinary research.