ORNL: Carrie Eckert: Tackling big problems using tiny organisms

Carrie Eckert applies her skills as a synthetic biologist at Oak Ridge National Laboratory to turn microorganisms into tiny factories that produce a variety of valuable fuels, chemicals and materials for the growing bioeconomy.

As lead for the laboratory’s Synthetic Biology Group, Eckert brings her passion for developing tools that accelerate bioengineering to a team focused on designing plants and microbes for a range of applications.

Eckert’s work puts her at the center of many Department of Energy projects with diverse goals. She leads the Rapid Genomics team for the Center for Bioenergy Innovation, or CBI, where scientists focus on creating hardier bioenergy crops and modifying microbes to convert plant material into biofuels and bioproducts. She contributes to many other efforts, including working with soil microbes to improve plant and ecosystem productivity, engineering microorganisms to breakdown and upcycle plastics, and assisting industry with modifying their organisms of choice to produce products.

She finds the variety energizing.

“If you look at the number of organisms I’ve worked with, it’s very many,” Eckert said. “I actually enjoy that because it keeps the research interesting.”

The common thread running through these projects is the need to connect genes with desirable traits and behaviors. To optimize characteristics such as a microbe’s tolerance for ethanol, Eckert and her colleagues must first identify the genetic fingerprint of that particular trait. A characteristic of interest can be tied to a change in the building blocks that make up DNA, such as a single nucleotide, or it could result from interactions between many genes.

“Gene function identification is one of the grand challenges in biology,” said Eckert. “We have easy access to DNA sequences, but connecting genotypes to phenotypes [or traits] is often a complex and time-consuming process.”

She is working with the laboratory’s experts in computational biology to apply machine learning and high-performance computing to speed the discovery process. The interdisciplinary team is also developing faster machine learning methods to guide development of gene editing tools.

Because each microbe requires unique genetic tools, much of Eckert’s work is focused on tailoring CRISPR-Cas technology for use in a variety of bacteria and fungi. CRISPR-Cas acts like a pair of tiny molecular scissors that snip and replace segments of DNA. It has quickly become the primary tool for bioengineering. Most CRISPR design tool development has concentrated on mammalian systems, so Eckert and her colleagues are creating new design rules and tools for its use in various wild microbes.

As part of her work for CBI, Eckert collaborated with other scientists to develop a CRISPR system for the bacteria Clostridium thermocellum. These microbes are naturally able to digest plant material, including lignin, a hard-to-break-down component that is often discarded as a waste byproduct of the plant-to-fuel conversion process. Being able to use the carbon-rich lignin to make more fuel would improve the economics of biofuel production.

There were no CRISPR systems available that worked at the high temperatures C. thermocellum favors, so Eckert and her colleagues developed one and identified other genes that improve the integration of DNA edits into the microbe’s genome. They cut the time to modify the organism in half and are working to improve C. thermocellum and other microbes’ efficiency at producing biofuels.

“We can make mutations in genomes that you would never see arise by chance,” Eckert said. “That allows us to get to the answers quite a bit faster.”

Brewing up success

Eckert has always loved science and learning about how things work. She entered college around the time that Dolly, the cloned sheep, was born, and that sparked her fascination with genetics. As she began her graduate studies at the University of Colorado, she considered a career in medical research. Her hands-on laboratory experiences during school sent her down a different path.

As an undergrad, Eckert worked with corn plants. She examined the genetic factors that make some crops more heat tolerant than others. She studied chromosomes using yeast and the cell cycle using frog eggs while pursuing her doctorate in molecular biology. She enjoyed the yeast far more than the frogs. That spurred her to look for other opportunities to work with microbes.

Eckert’s interest in yeast spilled over into her hobbies as well, and she has become an avid home brewer. One of her brews was chosen recently as best overall in a competition, winning her the chance to work with a brewery to scale it up and enter it into the Great American Beer Festival. Her recipe was inspired by a beer identified through mass spectrometry of an urn from an Egyptian tomb.

Cyanobacteria became Eckert’s focus after grad school when she accepted a postdoctoral position with the National Renewable Energy Laboratory, where she later transitioned to a staff position. Also known as blue-green algae, cyanobacteria are found in all types of water and thrive through photosynthesis like plants. Eckert’s initial project harnessed these organisms to produce hydrogen using carbon dioxide and light.

She continued to branch out while at NREL. She worked with diverse microbes and accepted a joint appointment with the University of Colorado Boulder, which led to a leadership role at the Renewable and Sustainable Energy Institute. She mentored research students at the university and was a strong supporter of their Women in Science and Engineering mentorship program.

“It can be difficult to be a woman in fields of science and engineering, so I think it is really important for women to have support,” said Eckert, a mother of two who started her family while in undergrad. “Knowing how to balance work life is important.”

Eckert was excited to accept a new position with ORNL and move to Tennessee this past summer. It was the opportunity to lead a group focused on synthetic biology and to work more closely with colleagues she’d collaborated with through CBI, the Secure Ecosystem Engineering and Design Science Focus Area, and other projects that drew her to Oak Ridge. She joined the staff in July and enjoys applying the laboratory’s world-class capabilities to developing biological solutions for complex problems such as the plastics crisis.

“Synthetic biology is dipping its toes in many areas, from bioenergy to drug discovery,” Eckert said. “As we develop genetic tools, we learn how to do things that are transferrable across many different problems and applications.”