Members of the iGEM team at the University of Rochester used bacterial cultures, pictured here frozen in liquid nitrogen, to create 3D bioprinted bacteria samples as part of their project to replicate chemicals found in plants. Credit: University of Rochester Photo / J. Adam Fenster
Rochester undergraduates have developed a 3D bioprinting system to replicate chemicals found in plants, including those threatened by climate change.
Imagine a world without plants. Although this extreme scenario has not become a reality, Earth is facing a worrying trend: the rapid depletion of potential plant-based medicines. Globally, tens of thousands of flowering plant species play vital roles in medicinal applications, but many of the pharmaceutical products dominating the U.S. market rely heavily on imported plant raw materials that require very specific climatic conditions for optimal growth.
The threat to many plant species is intensified by factors such as climate change, invasive pests and diseases, and agricultural practices that struggle to meet high demand for finished products.
To address these issues, a team of 10 University of Rochester undergraduates developed new technologies to more efficiently replicate useful chemicals found in plants, including those threatened by global climate change. Earth. Calling themselves “Team RoSynth,” the students created an affordable 3D printing system to optimize the production of in-demand plant-based medicines and pharmaceuticals.
In November, the team entered their research into the 2023 International Genetically Engineered Machine (iGEM) Competition, an event in which student-led teams from around the world compete to solve real-world problems using of synthetic biology. Synthetic biology takes advantage of engineering to build biological parts inspired by nature. The Rochester team’s project was nominated for Best Biomanufacturing Project and Best Equipment and received a gold medal, making them the third most recognized team in the United States. The team competed against 402 teams from six continents.
“The RoSynth team’s technology has enormous potential to advance the entire field of synthetic biology, enabling simple and accessible production of new engineered living materials,” says Anne S. Meyer, associate professor in the Department of biology and one of the advisors for the Rochester iGEM team.
An “ingenious” method of bioprinting hydrogels
The RoSynth team designed its 3D bioprinter to print hydrogels, gel-like substances composed of water and polymers that can hold and release biological molecules. The Rochester team’s system is unique because it prints genetically engineered bacteria and yeast into adjacent hydrogels, which are then immersed in a liquid nutrient broth. The complex work of making the final chemical is split between two different types of microbes, making the process easier and faster.
A key innovation is that yeast and bacteria must grow separately to prevent one microbe from growing more quickly and causing the slower-growing microbe to die; however, the two microbes must also be able to exchange molecules to construct the final chemical.
“To solve this tricky problem, the students came up with an ingenious solution,” says Meyer. “Yeast and bacteria were 3D bioprinted in hydrogels, so the microbes were separated from each other, but the molecules they produced could exchange freely.”
The approach results in the synthetic creation of plant-based chemicals, without the use of actual plants.
As a test, the team biochemically synthesized rosmarinic acid (RA). RA is commonly extracted from plants such as rosemary, sage and fern. It is used as a flavoring and in cosmetics and has also been shown to have antioxidant and anti-inflammatory properties. Although rosmarinic acid is not dangerous in itself, it was an ideal extract to test.
“Rosmarinic acid is a popular plant compound, but its production was neither toxic nor dangerous to the students,” says Meyer. “In addition, the manufacturing process is quite complex and consists of a large number of enzymes that act sequentially.”
A response to climate change
The team, entirely student-led with several faculty members as advisors, began brainstorming project ideas in early 2023. Inspired by the COVID-19 pandemic, climate change and location of Rochester near New York’s agricultural hubs, the team prioritized addressing climate impacts on plant-based chemical supplies.
“Since we are located in Rochester, which is adjacent to the Finger Lakes region, a major agricultural area of New York State, we thought about how the impact of climate change would cause crop yields to decline over the coming years and would have an impact on local supplies of plants and plant-based compounds,” explains Catherine Xie, specialist in molecular genetics.
Bioprinted bacteria created by Rochester undergraduates contain green fluorescent proteins that glow under ultraviolet light. Credit: University of Rochester Photo / J. Adam Fenster
Medha Pan, also a specialist in molecular genetics, adds: “Our iGEM team was focused on the climate crisis and agricultural shortages we face, especially in the COVID era. We have seen for ourselves the importance of having accessible and reliable medicines.
Examples of specific drugs that could benefit from the methods and technologies developed by the RoSynth team include aspirin, derived from willow bark, and taxol, an anticancer drug, developed by yew species that have been identified as needing protection.
An affordable bioprinter
Part of the team’s mission was to create an affordable bioprinter with an open source design to allow others to explore the synthetic creation of plant-based chemicals.
“A typical bioprinter costs more than $10,000, but we designed one for less than $500,” says biomedical engineering specialist Allie Tay. “We wanted to have a 3D bioprinter that would be accessible to laboratories to carry out this proof of concept with the molecules of their choice.”
The project is such that other scientists can modify the genes and genetic pathways of bacteria and yeast to produce virtually any plant-based chemical. The bioprinter design itself is available on the team’s Wiki page and includes a guide on how to build and use the printer so others can create and adapt the technology for various uses .
By combining nature and cutting-edge technology, the team has proven that undergraduate students can carry out groundbreaking projects in record time.
“Projects like these typically take years to develop for doctoral or graduate students,” Tay says, “and the fact that we are undergraduates and received from February to November – I think it’s a pretty big undertaking.”
Provided by the University of Rochester
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