Model-guided gene circuit design for engineering genetically stable cell populations in diverse applications

Journal of The Royal Society Interface, Journal Year: 2025, Volume and Issue: 22(223)

Published: Feb. 1, 2025

Maintaining engineered cell populations’ genetic stability is a key challenge in synthetic biology. Synthetic constructs compete with host cell’s native genes for expression resources, burdening the and impairing its growth. This creates selective pressure favouring mutations which alleviate this growth defect by removing gene expression. Non-functional mutants thus spread populations, eventually making them lose functions. Past work has attempted to limit mutation coupling survival. However, these approaches are highly context-dependent must be tailor-made each particular circuit retained. By contrast, we develop analyse biomolecular controller depresses mutant independently of mutated gene’s identity. Modelling shows how our design can deployed alongside various circuits without any re-engineering components, outperforming extant gene-specific mitigation strategies. Our controller’s performance evaluated using novel simulation approach leverages resource-aware modelling directly link circuit’s parameters population-level behaviour. design’s adaptability promises mitigate an expanded range applications, while analyses provide blueprint models design.

Language: Английский

Modern, Efficient, and Differentiable Transport Equation Models Using JAX: Applications to Population Balance Equations

Industrial & Engineering Chemistry Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 14, 2025

Language: Английский