In the realm of modern science, the synthesis of complex biological systems has always posed a challenge to researchers. However, Steve Abel, an esteemed associate professor in the Department of Chemical and Biomolecular Engineering at the University of Tennessee, Knoxville, is redefining the boundaries of this field. With a keen focus on cell-free biomanufacturing solutions, he seeks to simplify the intricacies of biological processes by stripping away the complexities of living cells. This innovative approach is becoming increasingly relevant in a landscape where traditional methods have fallen short in producing high-value biochemical products.
For over a decade, Abel has been at the forefront of utilizing computational and theoretical methodologies to unravel the fundamental physical interactions that govern molecular behavior in cell biology. His work is significant, as it not only helps in understanding these processes more clearly but also lays the groundwork for developing applications that can directly impact various industries—from pharmaceuticals to agriculture. Abel emphasizes that by employing simpler, cell-free systems, researchers can gain more definitive insights into biological processes without the overhead of cellular obstructions.
Abel’s groundbreaking research aligns seamlessly with the National Science Foundation’s (NSF) initiative known as Advancing Cell-Free Systems Toward Increased Range of Use-Inspired Applications (CFIRE). This initiative was designed to encourage collaborative efforts among experts from diverse fields to catalyze advancements in cell-free biomanufacturing technologies. In 2024, Abel applied to CFIRE and was notably one of the select 37 specialists invited to contribute. This exclusivity is a testament to his significant expertise and innovative approach to biomanufacturing.
Within the CFIRE workshop, Abel was instrumental in the development of not one, but two successful research proposals. The NSF recognized the innovative potential of these projects, providing Abel and his collaborators with a combined funding amount that underscores the significance of their work in the future of biomanufacturing. One of these ambitious projects is a $7.6 million initiative, led by the University of California, Irvine (UCI), that aims to leverage liquid phase separation to engineer specialized environments tailored for various enzymes within a single bioreactor.
In another impressive endeavor, Abel is also a participant in a larger CFIRE project steered by the Georgia Institute of Technology (Georgia Tech), which has attracted a whopping $9.2 million in funding. The project’s goal is to design modular metabolic reaction networks capable of facilitating the cell-free production of a diverse array of molecules. Collectively, these projects signify a tidal shift toward more efficient biomanufacturing techniques which hold vast implications for industries reliant on chemical production.
Abel and his team will receive a substantial $1.7 million funding slice over the next three years, reflecting the profound implications their research promises. He articulates the essence of collaborative effort within these projects, noting, “I like to work with people and be collaborative—it’s central to how I do science and research.” His collaborative spirit was evident in how seamlessly the various expertise of his colleagues merged to form a cohesive research strategy.
The first of Abel’s projects draws upon a physical principle rooted in the everyday experience of making salad dressing. This phenomenon, known as liquid-liquid phase coexistence, allows two immiscible liquids to exist together, separated by an interface. Abel elucidates this concept with a metaphor familiar to everyone: “It’s the technical term for how a salad dressing has droplets of oil suspended in vinegar.” By harnessing this principle, Abel’s team aims to create localized environments that enhance specific reactions crucial for synthesizing high-value molecules that are otherwise notoriously difficult to produce within traditional systems.
This pioneering approach aims to develop precursor molecules vital for the manufacture of valuable agrichemicals and pharmaceuticals by employing innovative techniques. Collaborators from other institutions, such as UCI’s Associate Professor Samanvaya Srivastava, will utilize synthetic polymers to fabricate two liquid phases that maintain stability. This multi-institutional collaboration is impressive, showcasing how interdisciplinary cooperation can lead to breakthroughs that institute changes in traditional manufacturing paradigms.
Meanwhile, Abel’s second project addresses an even larger challenge in biomanufacturing. The conventional process, which necessitates the translation of DNA into messenger RNA before being converted to proteins within a living cell, is inefficient. Living cells allocate a significant amount of their energy resources to growth and maintenance, while the desired products must be painstakingly isolated from a myriad of other biomolecules. This inefficiency can be a bottleneck for industries seeking to produce high-value biological compounds.
Ingenuity meets necessity in Abel’s collaboration with Georgia Tech Professor Mark Styczynski, which will lead to the development of eight modular cell-free reaction network units capable of enabling processes like transcription and translation. These modules would allow researchers to inventively combine and recombine them to formulate new and efficient biomanufacturing pathways. By returning the focus from live cells to tailored reaction networks, Abel’s work represents a paradigm shift toward greater efficiency in producing valuable products.
One of the remarkable aspects of this research is the mix of molecular components within these reaction modules. The reactor tank would house an intricate ‘soup’ of hundreds to thousands of different molecular structures, a daunting thought for many but an exciting prospect for Abel’s research team. Abel stresses that the ability to conceptualize and model such complex interactions is the key differentiator in effectively unlocking the potential of these biomanufacturing approaches.
With such convoluted systems, the role of computational modeling becomes indispensable. Abel’s expertise in mathematical modeling empowers his team to simulate these intricate interactions, thus enabling them to identify pivotal enzymes with significant influence across various parameters of reactor efficiency and yield. By understanding these interconnections, researchers gain insights that would be prohibitively costly or verging on impossible to acquire through traditional experimental means.
By integrating sophisticated mathematical models with experimental data, Abel and his team can streamline biomanufacturing processes, accentuating the most critical components and diminishing unnecessary complexities. In the landscape of biomanufacturing, such synergies contribute to a more nuanced understanding of the systems at play, pointing toward more feasible solutions for industrial challenges.
In summary, the work that Steve Abel and his collaborators are undertaking marks a significant crossroads in biomanufacturing research. With a commitment to deploying computational and theoretical frameworks alongside innovative experimental techniques, they are addressing fundamental inefficiencies in bio-production processes. As industries move toward a future that increasingly demands efficiency and sustainability, Abel’s research could very well pave the way for transformative solutions in how biomanufacturing is conceptualized and executed. His excitement for the collaborative nature of these projects is palpable, reflecting a broader vision of a scientific community united in tackling urgent global challenges.
Subject of Research: Cell-Free Biomanufacturing Technologies
Article Title: A New Frontier in Biomanufacturing: Pioneering Cell-Free Solutions
News Publication Date: October 2023
Web References: University of Tennessee, Georgia Institute of Technology, University of California, Irvine
References: Not applicable
Image Credits: University of Tennessee
Keywords
Life sciences, Cell biology, Applied sciences and engineering, Agriculture, Agricultural chemistry, Drug design, Biochemistry, Pharmacology, Drug development, Computational chemistry
