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Germinating Solutions

April 20, 2020

By Paul Alongi | Photography by Josh Wilson | 

Yeast might be Earth’s most underappreciated lifeform. These single-celled members of the fungi kingdom get plenty of credit for turning barley into beer, grapes into wine and wheat into bread. But their range might not be limited to the blue planet for long.

Mark Blenner, the McQueen-Quattlebaum Associate Professor in the Department of Chemical and Bimolecular Engineering at Clemson University, is engineering yeast to do things nature hasn’t yet figured out.

The potential is wide-ranging. Blenner is helping yeast produce two very different products —omega-3 supplements and polyester — that astronauts could use on missions to Mars. He is also using yeast to explore new ways of developing drugs, and to create sensors that would help search for radiation from nuclear weapons production.

For Blenner, the research is a platform to teach students how to ask and answer critical questions. He also sees his work as a potential catalyst for a cutting-edge industry that South Carolina could lead.

His colleagues are recognizing his work. Last spring, Blenner was named Clemson University Junior Researcher of the Year. He conducted research in the fall at NASA’s Ames Research Center. Over the summer, he received the Presidential Early Career Award for Scientists and Engineers, the nation’s highest honor bestowed on young faculty.

“I use him as an example to my current students,” says Scott Banta, a professor of chemical engineering at Columbia University and Blenner’s former Ph.D. adviser. “If you want to go into academia, this is what it should look like.”

Blenner likens his work to installing software in a computer. He and his students use bacteria to construct DNA — the software — and then install it into the yeast — the hardware — to create the desired molecule.

The scientific community’s advances in DNA sequencing and synthesis over the past 10 years have helped break open the field to new possibilities, Blenner says.

“I think we’re going to see a lot more solutions to problems that are microbial based,” Blenner says. “And I think it’s going to be part of the solution to helping us survive on Mars and other planets.”

YEAST IN SPACE

The work that has earned Blenner the most headlines focuses on how yeast could help astronauts reach Mars and survive once they land. Yeast would act as a recycling center, allowing astronauts to reuse molecules that are plentiful on Earth but will be precious beyond the atmosphere that sustains life.

One area where Blenner sees promise is using yeast to produce omega-3 fatty acids. The essential nutrients are critical to the brain and help prevent heart disease. On Earth, omega-3 fatty acids are a dwindling resource available mostly from fish, and from supplements, such as fish oil, but their shelf life is limited to about two years. Any supplies carried from Earth wouldn’t be sufficient for a mission that lasts longer.

This is where a species of yeast, Yarrowia lipolytica, would come into play. The yeast would be genetically modified to create omega-3 fatty acids and would need two main ingredients to grow: nitrogen and carbon. Astronauts could produce both from their own bodies.

For nitrogen, they could harvest urea from urine. Carbon could come from the carbon dioxide in their own breath or the Martian atmosphere. Put it all together, and astronauts could make their own nutritional supplements to keep themselves healthy planets from home.

Another strain of Yarrowia lipolytica could be engineered to create biopolymer PHA, a type of polyester similar to the kind used to make clothes. But instead of using the polyester to weave double-knit suits, astronauts could feed it into a 3D printer to make tools.

Blenner says the NASA-funded project is progressing well and that his major focus now is on yeast cells themselves: “One of the common ingredients in microbial growth media is something called yeast extract, which is basically partially degraded yeast cells. You need a mountain of cells to get a product from the cells, and that’s a lot of good carbon, nitrogen, phosphorous and oxygen that could be put back into the manufacturing process. I’m evaluating now the chemical composition of the different cell biomasses and seeing how much reusability you can get out of them before perhaps toxic things start to accumulate in that biomass.”

ENGINEERING BETTER MEDICINES

Blenner’s work with yeast could also help tease new drugs out of plants.

Many plants hold promising pharmaceutical compounds but in quantities too small to develop into marketable drugs. Plant growth cycles are slow and subject to seasonal and regional variation in output and quality. Further, land use for the compounds and other natural products often competes with land use for much-needed food.

The antimalarial drug artemisinin, for example, takes over 12 months to produce from planting to extraction, whereas the same can be done in a week with yeast.

Blenner says that placing a plant gene in yeast can be done inexpensively. However, the yeast often fails to make protein correctly, and the critical challenge in the new research is to figure out why, he says. The team plans to analyze the genetically modified yeast with bioinformatics — computer algorithms that help researchers understand large sets of biological data.

“In this case, we’re looking at changes in the number of different RNA molecules that are made in each cell,” Blenner says. “RNA molecules are the precursor to making protein. We can use bioinformatics tools to count the number of RNA molecules for each gene in the entire genome of the cell, and if we know what most of those genes do, we can start to understand what the cell does in response to making new proteins.”

The antimalarial drug artemisinin, for example, takes over 12 months to produce from planting to extraction, whereas the same can be done in a week with yeast.

SEARCHING FOR NUCLEAR WEAPONS

The Blenner team is also collaborating on research aimed at creating devices that sound like they could have come out of the latest James Bond epic. The devices would be disguised, maybe as leaves, and search for evidence of nuclear-weapons production.

But before it’s ready for the real-life 007, researchers need to show the approach could work. They are now developing some very simple sensors that will show how yeast and bacteria respond to different types of radiation sources, such as plutonium and a type of radioactive nickel. Then they need to see if the information they are gathering can be put together to tell the difference between natural radiation and weapons material.

“I was pleasantly surprised to see we’re getting very unique signatures from the couple of different radioactive isotopes we’ve tried so far,” Blenner says. “I think that has a lot of potential for being transitioned to an end user. Certainly, the findings are important for developing the feasibility of the approach.”

SPARKING NEW INDUSTRY

Blenner is now starting to experiment with a species of yeast, Cutaneotrichosporon oleaginosus, that remains largely unexplored. It has similar properties as Yarrowia lipolytica but has a set of additional capabilities, according to Blenner.

“It grows under a wider range of conditions, it grows faster, it makes more lipids,” he says. “It’s bigger, better, stronger, faster than Yarrowia lipolytica. We’ve even shown it can degrade some of nature’s toughest biopolymers — something called lignin.”

Lignin, the substance that gives trees their strength, ends up as a byproduct of wood-processing with few uses, other than burning it, Blenner says. But it could be possible to engineer Cutaneotrichosporon oleaginosus to turn lignin into omega-3 fatty acids, biofuel or biopolymers.

Blenner took leave from his Clemson duties in fall 2019 to conduct research at NASA’s Ames Research Center in Silicon Valley. While his efforts were directed at the stars for a few months, he still had some ideas brewing for his work back in South Carolina.

Blenner says his research has the potential to catalyze a center dedicated to biomanufacturing and synthetic biology, involving a small group of faculty at Clemson already focused on the field.

“I think South Carolina is poised to transform into a microbial-industrial-biotech hub,” he says. “I think all the components are there — the right governmental policies, the workforce. We need some kind of sustained effort to build on the successes we’ve had and catalyze this new industry and industrial growth in the region.”

David Bruce, chair of the Department of Chemical and Biomolecular Engineering, says the quality he likes best about Blenner is that he is forward-thinking:

“Mark Blenner is constantly thinking about how he can do the next experiment, how he can teach his class better, what the students are going to need tomorrow and where the research in the field is going. He’s constantly trying to stay ahead of the game — and that’s impressive.”

INVESTING IN THE NEXT GENERATION

Mark Blenner oversees one of the biggest labs in Clemson’s College of Engineering, Computing and Applied Sciences: 16 undergraduates, one master’s student, nine doctoral students and four postdoctoral researchers.

Blenner says that when he works with undergraduates, he tries to be empathetic to their needs and stresses, yet maintain high expectations: “In some places, undergraduates clean glassware in the lab, and that’s all. I want students to feel like they have a purpose and know what their work is going to contribute to the group and the scientific community.”

Blenner’s work with students is also planting the seeds for a more diverse future in chemical engineering. A team he led recruited eight Ph.D. students from groups underrepresented in engineering, including women and African Americans.

Those students are now working toward doctoral degrees in chemical engineering and plan to pursue careers in education and research, with a goal of being role models for others who follow them.

“If you develop six faculty members, you’re making six people who are going to influence about 100 students a year for the next 30 or 40 years,” Blenner says. “The initial investment creates 4,000 engineers for each faculty. You’re basically investing in better preparing the next generation of engineers and scientists.”



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