2025/04/15 by Ling-Wei Kong, Wenjia Shi, Xiao‐Jun Tian +1 · 1 voice
Biochemistry, Genetics and Molecular Biology · #Gene Regulatory Network Analysis #Receptor Mechanisms and Signaling #Single-cell and spatial transcriptomics
paper · doi:10.7554/elife.89170.3
openalex publication_date 2025/04/15 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
The successful integration of engineered gene circuits into host cells remains a significant challenge in synthetic biology due to circuit–host interactions, such as growth feedback, where the circuit influences cell growth and vice versa. Understanding the dynamics of circuit failures and identifying topologies resilient to growth feedback are crucial for both fundamental and applied research. Utilizing transcriptional regulation circuits with adaptation as a paradigm, we systematically study more than 400 topological structures and uncover various categories of failures. Three dynamical mechanisms of circuit failures are identified: continuous deformation of the response curve, strengthened or induced oscillations, and sudden switching to coexisting attractors. Our extensive computations also uncover a scaling law between a circuit robustness measure and the strength of growth feedback. Despite the negative effects of growth feedback on the majority of circuit topologies, we identify several circuits that maintain optimal performance as designed, a feature important for applications.