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New research institute will utilize cell-free systems for global needs

Northwestern and U.S. Army collaborate to develop point-of-need products
cell-free biology
PNAS illustration by Dave Cutler.

Northwestern University has established a new basic science research institute, the Cell-Free Biomanufacturing Institute, in partnership with the U.S. Army. Its goal is to accelerate the development of synthetic biology technologies for the creation of on-demand and point-of-need products useful to both society and the Army.

With a focus on cell-free systems, the interdisciplinary institute will develop a powerful infrastructure to design, create and manufacture molecules, materials and sensors that are unattainable through traditional approaches. It also will train the next generation of scientists and engineers and act as an engine for entrepreneurial growth in Illinois in the area of synthetic biology, a relatively young discipline that uses tools and concepts from physics, engineering and computer science to build new biological systems.

“There is an emerging and growing interest in being able to partner with biology to make what is needed, where and when it is needed, on a sustainable and renewable basis,” said Northwestern’s Michael Jewett, an expert in synthetic biology and director of the new institute. 

“This includes everything from medicines to sustainable products to materials we might use every day,” he said. “This opportunity, enabled by synthetic biology and the ability to program the living world, is really what this new partnership with the Army’s Chemical Biological Center is about.” 

Jewett is the Walter P. Murphy Professor of Chemical and Biological Engineering in the McCormick School of Engineering and director of Northwestern’s Center for Synthetic Biology, one of about 40 University research institutes and centers (URICs) attracting talent from across multiple Northwestern schools.

In an effort that builds off Northwestern’s strengths collaborating at the intersection of disciplines and institutionally supported centers, Jewett’s team of 12 Northwestern faculty from McCormick and the Weinberg College of Arts and Sciences will work with a team led by research biologists Patricia Buckley and Matthew Lux of the U.S. Army Combat Capabilities Development Command Chemical Biological Center Research & Technology Directorate. 

“We’re excited by the opportunity to work with Northwestern on developing a biomanufacturing capability that can lead to the ability to produce materials critical to the Army mission quickly and close to the theater of operations,” said Buckley, who serves as the biochemistry branch chief for the Chemical Biological Center. “This is a partnership that can change the way Department of Defense (DoD) provides critical materials to its personnel.”

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We are using the components of the cell but not a living organism to make things we need.

Michael Jewett

“Biomanufacturing allows for agility and diversity that cannot be achieved in traditional petrochemical production,” said Jared DeCoste, a research chemist with the Chemical Biological Center. “For the DoD, there’s a need to produce small-batch specialty chemicals, which means we may be producing one chemical or material today but need to shift quickly to something else. With biomanufacturing you can turn over your equipment quickly and introduce a new genetically modified organism to produce your desired product.”

The collaborative research institute is focused on developing a specific type of biomanufacturing, called cell-free biomanufacturing. This approach offers a new production model without the constraints of working with living organisms. Instead of manufacturing in a living cell, as is done to produce insulin from yeast, for example, cell-free biology activates basic cellular processes to make desired products without live intact cells. 

mRNA vaccines — now familiar around the world due to the pandemic — are made using a cell-free biomanufacturing process, but not many products have been made using this approach yet. Researchers with the new institute are eager to explore new applications of cell-free systems that could potentially transform the bioeconomy.

The Department of Defense is particularly interested in developing materials, diagnostics and sensors. Examples include optical materials for adaptive camouflage and cell-free sensors for diagnostics for environmental sampling, such as water or food quality.

“We are using the components of the cell but not a living organism to make things we need,” Jewett said. “Cell-free systems provide an unprecedented and otherwise unattainable freedom of design to modify and control biological systems.”

Some of the key limitations to developing cell-free biomanufacturing approaches have been cost and scale, Jewett said, areas which the research institute will address. Other focus areas include bolstering domestic supply chains, devising strategies to create novel functional materials, new diagnostics and sensing technologies, and developing a robust synthetic biology workforce. In addition, some of the cell-free technologies may facilitate equitable access to biomanufacturing across the world in ways that haven’t been possible before.

“I’m excited about the opportunity to change the paradigm with which we manufacture products using cell-free systems,” Jewett said. “It opens up the possibility of decentralized manufacturing approaches, to allow people to make products where and when they are needed. Biology is everywhere. It’s the ultimate decentralized technology.”

In addition to Jewett, the Northwestern team includes chemical engineer Linda Broadbelt, chemist Omar Farha, materials chemist Nathan Gianneschi, biological engineers Neha Kamat and Ashty Karim, synthetic biologist Julius Lucks, applied mathematician Niall Mangan, biochemist Milan Mrksich, computational scientist Monica Olvera de la Cruz, protein engineer Danielle Tullman-Ercek and metabolic engineer Keith Tyo.

The DoD team includes Buckley, Lux and DeCoste, as well as chemical engineer Marilyn Lee and research biologist Aleksandr Miklos.