Dr. Cong Trinh
Department of Chemistry and Biomolecular Engineering
University of Tennessee, Knoxville

MODULAR CELL DESIGN PRINCIPLES: THEORY, COMPUTATION, AND EXPERIMENTAL DEMONSTRATIONS

ABSTRACT: Modular design is a governing principle in natural and engineered systems, enabling rapid, efficient, and reproducible construction and maintenance. While the theory and application of modular design are developed in non-biological engineering disciplines, the field is still at a nascent stage to understand and harness modular design across biological scales. In this talk, I present our recent research progress on the development of theory, mathematical formulation and computation, and experimental validation of modular biosystems design. Microorganisms can be engineered to function as microbial cell factories to produce a large space of fuels, chemicals, and materials in a sustainable and renewable manner. The current technology for microbial biocatalyst development, however, remains laborious and costly to implement, precluding its widespread adoption. To overcome this roadblock, we propose to adapt the principles of modular design that drive innovation, efficiency, and predictability across modern engineering disciplines to the fields of synthetic biology and metabolic engineering for microbial biocatalyst development. These microbial biocatalysts can be rapidly and systematically built from a modular (chassis) cell strongly coupled with exchangeable pathway modules that enable programmed functions for overproduction of desirable chemicals with minimal requirement of iterative strain optimization cycles. We formulate a mathematical and computational framework that enables systematic design of modular cells based on the metabolic pathway analysis and Pareto optimization theory for tenths to hundreds of modules in various organisms. Using Escherichia coli as a testbed, we demonstrate it is feasible to design a modular cell(s) capable of synthesizing in a large, biochemically diverse library of molecules at high yields and rates with minimal tradeoff of modularity, efficiency, and robustness. By identifying reaction usage patterns for different modules in the modular cell, we elucidate modular organization of the designed cells, defining the interfaces between a modular cell and its production modules. Our analysis reveals the broad pathway compatibility of the designed modular cell is enabled by the natural modularity and flexible flux capacity of endogenous core metabolism. To validate the modular cell design experimentally, we design and create an E. coli modular cell for switchable efficient biosynthesis of designer alcohols and esters from fermentable sugars that have broad utility as fragrances, flavors, solvents, and fuels. We demonstrate metabolic coupling between the modular cell and production modules can be modulated to enhance target product production and have important implications for enzyme pathway selection and evolution.

BIO:  Dr. Cong T. Trinh is an Associate Professor in the Department of Chemical and Biomolecular Engineering at The University of Tennessee, Knoxville. Dr. Trinh earned his B.S in Chemical Engineering (summa cum laude, honors thesis) with minors in Chemistry and Mathematics from The University of Houston and his PhD in Chemical Engineering from The University of Minnesota-Twin Cities with Prof. Friedrich Srienc. He then worked as a postdoctoral scholar with Profs. Douglas Clark and Harvey Blanch at The University of California, Berkeley. 

Dr. Trinh works in the areas of systems and synthetic biology, metabolic and biochemical engineering, and microbial physiology. His research aims to fundamentally understand complex cellular systems and to develop novel experimental and computational tools to control these systems for biotechnological applications. Research thrust 1 is to understand the principles of modular design in biological systems and develop the transformative MODCELL (Modular Cell) technology to engineer modular chassis cells for rapid development of novel microbial biocatalysts for industrial biocatalysis.  Research thrust 2 is to understand the mechanisms to inactivate pathogens and develop the transformative ViPaRe (Virulent Pathogen Resistance) technology to effectively combat rapidly evolving and resistant pathogens. Research thrust 3 is to understand the mechanisms of cellular robustness against environmental perturbation and develop effective defensive tools to boost cellular robustness for applications from disease prevention to novel biocatalysis.

Dr. Trinh has co-authored > 50 peer-reviewed papers, 1 patent, and several pending and provisional patents and co-edited one book. He received several awards including Thomas & Ruth Clark Excellence in Chemical Engineering Award (2021), DARPA’s YFA Director Fellowship (2019), TCE Teaching Fellow Award (2019), Chancellor Research & Creative Achievement/Professional Promise (2018), TCE Professional Promise in Research Award (2018), Ferguson Faculty Fellow (2018-present), DARPA YFA Award (2017), ASEE New Researcher Award (2017), CBE Outstanding Teaching Award (2014, 2017), NSF CAREER Award (2016), Thomas & Ruth Clark Chemical Engineering Excellence in Teaching Award (2016), CoE Professional Promise in Research Award (2016), and Professional Development Award (2014).

Dr. Trinh is a board member for several peer-reviewed journals including Frontiers in Systems Microbiology; Frontiers in Microbial Physiology and Metabolism; Biochemical Engineering Journal, Processes, and BioDesign Research. He is an active member of the International Metabolic Pathway Analysis (MPA) Conference since 2015 and served as the chair of 2021 MPA conference.