通过可编程基因转移实现基因调控的群体水平放大。
Population-level amplification of gene regulation by programmable gene transfer.
作者信息
Son Hye-In, Hamrick Grayson S, Shende Ashwini R, Kim Kyeri, Yang Kaichun, Huang Tony Jun, You Lingchong
机构信息
Department of Biomedical Engineering, Duke University, Durham, NC, USA.
Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, USA.
出版信息
Nat Chem Biol. 2025 Jan 8. doi: 10.1038/s41589-024-01817-9.
Engineering cells to sense and respond to environmental cues often focuses on maximizing gene regulation at the single-cell level. Inspired by population-level control mechanisms like the immune response, we demonstrate dynamic control and amplification of gene regulation in bacterial populations using programmable plasmid-mediated gene transfer. By regulating plasmid loss rate, transfer rate and fitness effects via Cas9 endonuclease, F conjugation machinery and antibiotic selection, we modulate the fraction of plasmid-carrying cells, serving as an amplification factor for single-cell-level regulation. This approach expands the dynamic range of gene expression and allows orthogonal control across populations. Our platform offers a versatile strategy for dynamically regulating gene expression in engineered microbial communities.
对细胞进行工程改造以感知和响应环境信号,通常侧重于在单细胞水平上最大化基因调控。受免疫反应等群体水平控制机制的启发,我们利用可编程的质粒介导基因转移,展示了细菌群体中基因调控的动态控制和放大。通过Cas9核酸酶、F接合机制和抗生素选择来调节质粒丢失率、转移率和适应性效应,我们调节携带质粒细胞的比例,作为单细胞水平调控的放大因子。这种方法扩展了基因表达的动态范围,并允许对不同群体进行正交控制。我们的平台为动态调节工程微生物群落中的基因表达提供了一种通用策略。