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<p>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.</p><p></p>

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Population-level amplification of gene regulation by programmable gene transfer

  • 期刊论文

  • 发表日期：

    2025年1月8日

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  • Hye-In Son,
  • Grayson S. Hamrick,
  • Ashwini R. Shende,
  • Kyeri Kim,
  • Kaichun Yang,
  • Tony Jun Huang,
  • Lingchong You

摘要

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.