The ability to control gene expression across a wide range is crucial for many fields, including bioengineering, disease detection, and environmental monitoring. Research led by Lingchong You, PhD, professor of biomedical engineering and molecular genetics and microbiology, developed a system to better regulate gene expression that could be applied to biosensors, toxin production, and metabolic pathway regulation.
Inspired by the immune system, You and team’s ADEPT system (Amplification of Dynamic gene Expression by Programmable gene Transfer) amplifies or suppresses specific cell populations in response to environmental cues.
The system works by regulating the behavior of plasmids, which are small, circular DNA molecules, Plasmids are used in molecular biology to build gene circuits because they are easy to modify and can boost gene expression. However, plasmid copy numbers can fluctuate, causing inconsistent gene expression within bacterial populations.
By balancing CRISPR-Cas-mediated cutting and gene transfer, ADEPT dynamically controls both the plasmid copy number within individual cells and the fraction of plasmid-carrying cells in a population, thereby tuning collective gene expression with an amplified dynamic range.
ADEPT can control gene expression in microbial communities by regulating plasmid behavior, such as their transfer, loss, and influence on cell function. Unlike traditional methods that operate at the single-cell level, ADEPT enables gene expression control across entire populations, allowing for much greater flexibility and scalability.
“Stable gene circuits enhance the reliability of biosensors, bioproduction processes, and therapeutic applications,” You said. “ADEPT achieves this by lowering plasmid loss rates and reducing the metabolic burden on host cells.”
ADEPT has already demonstrated its effectiveness in regulating gene expression and has been tested on a tetrathionate (TTR) biosensor, a diagnostic tool relevant to inflammatory bowel disease. This highlights ADEPT’s potential for tuning gene expression in real-world applications. As research progresses, ADEPT could be expanded to engineer complex microbial communities, providing a powerful tool for synthetic biology, environmental monitoring, and biomedicine.
“The flexibility of ADEPT opens up many possibilities,” You said.