不连贯的合并网络,用于强大的比率基因表达反应。
Incoherent merger network for robust ratiometric gene expression response.
发表日期:2023 Feb 25
作者:
Ukjin Kwon, Hsin-Ho Huang, Jorge L Chávez, Kathryn Beabout, Svetlana Harbaugh, Domitilla Del Vecchio
来源:
NUCLEIC ACIDS RESEARCH
摘要:
比例响应输出与两个输入值的大小比例成正比。比例计算在自然界中已被观察到,并且在智能益生菌和组织细胞发展中也需要。在这里,我们利用不一致合并网络在大肠杆菌中实现了比例基因表达响应。在该网络中,一个输入分子激活了输出蛋白的表达,而另一个分子激活了一个增强输出降解的中间蛋白。当降解速率为一阶且比稀释速率更快时,输出响应在广泛的输入分子水平比例范围内呈线性,并且R2接近1.响应灵敏度可以通过改变输出的翻译速率来定量调节。此外,比例响应对影响基因表达的细胞组分的全局扰动具有鲁棒性,因为此类扰动通过不一致的前馈回路对输出产生影响。这项工作展示了一种新的分子信号处理机制,适用于对细胞内环境具有鲁棒性的多重感知和响应电路。© 作者(2023)。由牛津大学出版社代表核酸研究出版。
A ratiometric response gives an output that is proportional to the ratio between the magnitudes of two inputs. Ratio computation has been observed in nature and is also needed in the development of smart probiotics and organoids. Here, we achieve ratiometric gene expression response in bacteria Escherichia coli with the incoherent merger network. In this network, one input molecule activates expression of the output protein while the other molecule activates an intermediate protein that enhances the output's degradation. When degradation rate is first order and faster than dilution, the output responds linearly to the ratio between the input molecules' levels over a wide range with R2 close to 1. Response sensitivity can be quantitatively tuned by varying the output's translation rate. Furthermore, ratiometric responses are robust to global perturbations in cellular components that influence gene expression because such perturbations affect the output through an incoherent feedforward loop. This work demonstrates a new molecular signal processing mechanism for multiplexed sense-and-respond circuits that are robust to intra-cellular context.© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.