Engineering Tunable, Low Latency Spatial Computation with Dual Input Quorum Sensing Promoters

IF 3.7 2区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS ACS Synthetic Biology Pub Date : 2024-05-23 DOI:10.1021/acssynbio.4c00068
Jure Tica, Haobin Chen, Shulei Luo, Manman Chen and Mark Isalan*, 
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Abstract

Quorum sensing signals have evolved for population-level signaling in bacterial communities and are versatile tools for engineering cell–cell signaling in synthetic biology projects. Here, we characterize the spatial diffusion of a palette of quorum sensing signals and find that their diffusion in agar can be predicted from their molecular weight with a simple power law. We also engineer novel dual- and multi-input promoters that respond to quorum-sensing diffusive signals for use in engineered genetic systems. We engineer a promoter scaffold that can be adapted for activation and repression by multiple diffusers simultaneously. Lastly, we combine the knowledge on diffusion dynamics with the novel genetic components to build a new generation of spatial, stripe-forming systems with a simplified design, improved robustness, tuneability, and response time.

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利用双输入法定人数感应促进器设计可调谐、低延迟的空间计算。
法定量感应信号是细菌群落中用于群体级信号传递的进化信号,也是合成生物学项目中用于细胞间信号传递工程的多功能工具。在这里,我们描述了一系列法定人数感应信号的空间扩散特性,并发现它们在琼脂中的扩散可以通过分子量的简单幂律来预测。我们还设计了新型双输入和多输入启动子,它们能响应法定人数感应扩散信号,可用于工程基因系统。我们设计了一种启动子支架,可同时被多个扩散器激活和抑制。最后,我们将扩散动力学知识与新型基因元件相结合,构建了新一代空间条纹形成系统,该系统设计简化,鲁棒性、可调性和响应时间均得到改善。
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来源期刊
CiteScore
8.00
自引率
10.60%
发文量
380
审稿时长
6-12 weeks
期刊介绍: The journal is particularly interested in studies on the design and synthesis of new genetic circuits and gene products; computational methods in the design of systems; and integrative applied approaches to understanding disease and metabolism. Topics may include, but are not limited to: Design and optimization of genetic systems Genetic circuit design and their principles for their organization into programs Computational methods to aid the design of genetic systems Experimental methods to quantify genetic parts, circuits, and metabolic fluxes Genetic parts libraries: their creation, analysis, and ontological representation Protein engineering including computational design Metabolic engineering and cellular manufacturing, including biomass conversion Natural product access, engineering, and production Creative and innovative applications of cellular programming Medical applications, tissue engineering, and the programming of therapeutic cells Minimal cell design and construction Genomics and genome replacement strategies Viral engineering Automated and robotic assembly platforms for synthetic biology DNA synthesis methodologies Metagenomics and synthetic metagenomic analysis Bioinformatics applied to gene discovery, chemoinformatics, and pathway construction Gene optimization Methods for genome-scale measurements of transcription and metabolomics Systems biology and methods to integrate multiple data sources in vitro and cell-free synthetic biology and molecular programming Nucleic acid engineering.
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