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Paul Abraham: From exploring proteins to informing biosystems design

Topic: Materials

Systems biologist Paul Abraham uses his fascination with proteins, the molecular machines of nature, to explore new ways to engineer more productive ecosystems and hardier bioenergy crops.

Proteins were Abraham’s first love when he came to Oak Ridge National Laboratory as an undergraduate seeking research experience while pursuing pre-med at the University of Tennessee.

“The genome of an organism gives clues to its potential behaviors and traits, but the proteins — the products of that genome — are where the rubber really meets the road,” Abraham said. “By studying proteins and characterizing them, we gain fundamental knowledge that allows us to redesign proteins, so they perform new functions or serve new purposes.”

Abraham has special expertise, built over his years working with colleagues at the laboratory, that he uses to unlock new knowledge about proteins and their functions. The group employs state-of-the-art mass spectrometry, a technology that accurately measures the identities and fragmentation of molecules at very high resolution. This technology is instrumental in studying how proteins influence the physiology and behaviors of plants and microbes as individuals or communities.

When Abraham first applied to the laboratory after seeing a flier for an ORNL undergraduate study program hanging outside his classroom, he had only heard of mass spectrometry in connection with forensic investigations. Little did he know that this capability would put him at the center of many major research programs, such as the Center for Bioenergy Innovation and the Plant-Microbe Interfaces Science Focus Area led by ORNL.

Collaborating across disciplines

Abraham collaborates regularly with plant biologists, microbiologists, ecologists, geneticists, engineers, and computational scientists on challenging scientific questions. His measurements provide critical data to inform and test new hypotheses on how plants and microbes adapt to changing environments.

“I get a lot of joy out of running these measurements on a daily basis, but I feel most accomplished when we take that one measurement and integrate it across a lot of different scientific disciplines,” Abraham said. “I think that's what ORNL is all about: making new discoveries through interdisciplinary research and collaboration.”

He and his colleagues are currently developing new tools for an emerging field focused on micro proteins, which are proteins made of 100 amino acids or less. The science is evolving to show these tiny proteins can have a big impact on biological systems. Abraham recently demonstrated a method to reliably recover micro proteins and accurately quantify them.

“That was fun,” he said. “I really enjoy chances like this to pioneer new techniques in emerging fields.”

Abraham’s fascination with proteins and the scope and variety of the research has kept him engaged at the laboratory throughout his graduate and postdoctoral studies and now as a staff researcher in the Biological Mass Spectrometry group. A Knoxville native, he has occasionally wondered if he should work a stint in a different locale, but he’s always dismissed the idea. “At least for this technology that we’re using in our research, I don’t feel I could make as big an impact anywhere but ORNL,” Abraham said.

Branching into biodesign, biosecurity

Abraham describes ORNL as a “place full of opportunities.” He grabbed one such chance as a new staff member by submitting a research proposal to receive Laboratory Directed Research and Development funds. The laboratory approved his idea, and Abraham along with a small team of researchers have successfully parlayed that effort into a bigger pilot scale project and a new Science Focus Area for the Department of Energy.

The effort focuses on secure ecosystem engineering and design, and it began with a small LDRD project called Lock and Key. Abraham and his team created a method to trigger the now widely used CRISPR/Cas9 genome editing tool to target itself and self-destruct. By adding an additional step to the process, this lock-and-key system can also be turned off if there is a desire to further optimize a genome using CRISPR/Cas9. Recently, his team created a way to detect, in real-time, whether the CRISPR tool is active in a cell.

Abraham and his colleagues are using these biodesign tools along with mass spectrometry and high-performance computing to advance our fundamental understanding of biological systems and explore ways to engineer more safe, reliable, and productive ecosystems.

His expanding focus on biodesign includes working with colleagues to examine the barriers that prevent new organisms from entering an ecosystem. The research aims to create ways of safely and securely introducing new microbes into managed ecosystems to achieve beneficial effects such as improving the drought tolerance and resilience of bioenergy crops.

Understanding how microbial pests enter ecosystems and developing ways to strengthen the barriers against them is another aspect of this research. Abraham and team are studying a fungal pathogen called Septoria that has migrated across the United States and now threatens poplar plantations throughout the Pacific Northwest.

In thinking about the way his science focus has evolved, Abraham credits ORNL and the LDRD program for giving him opportunities to “step outside my comfort zone and explore new science.”

In his spare time, Abraham and his family enjoy the nearby Smoky Mountains where he shares his love of the outdoors with his two young children.

UT-Battelle manages ORNL for DOE’s Office of Science. The single largest supporter of basic research in the physical sciences in the United States, the Office of Science is working to address some of the most pressing challenges of our time. For more information, please visit https://www.energy.gov/science.