Building real-time control for engineered biological systems
Dr. Chelsea Hu is developing new tools that combine real-time feedback, device engineering and mathematical modeling to help scientists better understand and control engineered biological systems
Scientists can engineer living cells to perform useful tasks, from producing medicines and sustainable chemicals to detecting disease. Unlike traditional engineered systems, living cells are constantly changing as they grow, making their behavior difficult to predict and control.
Dr. Chelsea Hu, assistant professor in the Artie McFerrin Department of Chemical Engineering at Texas A&M University, is developing new tools that help researchers better understand and control these dynamic biological systems.
When engineered cells — cells that have gone through gene editing — grow and divide, they naturally change how they function. Because of these changes, the same external signal can produce different biological responses over time, making it difficult for scientists to consistently direct cell behavior or optimize biological production processes.
Hu’s research combines device engineering, real-time feedback control and mathematical modeling to address this challenge, giving researchers practical tools to study how engineered cells behave and design more reliable biological systems.
The approach applies optogenetics, a technique that uses light to control specific activities inside living cells. While researchers have developed optogenetic systems that allow cells to respond to light, continuously measuring those responses and automatically adjusting the light in real time — a strategy known as closed-loop control — has remained technically challenging and often requires specialized equipment.
In a recent study, Hu and her team developed LED-Embedded Microplate for Optogenetic Studies (LEMOS), a laboratory platform that makes real-time optogenetic feedback control more accessible to synthetic biology researchers.
The system combines programmable LED lights with continuous measurements of cell growth and gene expression — the process by which cells use genetic information to produce proteins and carry out biological functions.
Rather than applying a fixed light pattern throughout an experiment, LEMOS continuously measures how cells respond and automatically adjusts the light in real time, allowing researchers to maintain more consistent control as cells grow.
“We can use light to regulate gene expression inside living cells,” Hu said. “This could eventually help improve production yield, reduce stress on the cells and make biological manufacturing more reliable.”
Hu’s team also developed Gene Expression Across Growth Stages (GEAGS), a mathematical modeling framework that explains how changes in cell growth influence gene expression and, ultimately, the performance of feedback control systems.
“As cells grow, they naturally change how they express genes,” Hu said. “That means the same light input can produce different cellular responses at different stages of growth. To design effective feedback control systems, we needed a model that accounts for those changes.”
LEMOS and GEAGS provide complementary tools for studying engineered cells in dynamic environments. By combining real-time feedback with mathematical models that account for how cells change as they grow, the research addresses one of synthetic biology’s central challenges: Living systems are constantly changing, so effective control strategies must adapt with them.
The work could improve the reliability and efficiency of biological manufacturing, where engineered cells are used to produce products such as medicines, fuels and specialty chemicals. The same control principles could also help researchers design therapeutic cells that respond dynamically to changes inside the human body.
By Raven Wuebker, Artie McFerrin Department of Chemical Engineering, Texas A&M University
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Journal
ACS Synthetic Biology
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