Chen Ming-Tang, Weiss Ron
Department of Electrical Engineering, Princeton University, J319, Engineering Quadrangle, Olden Street, Princeton, New Jersey 08544, USA.
Nat Biotechnol. 2005 Dec;23(12):1551-5. doi: 10.1038/nbt1162. Epub 2005 Nov 20.
The construction of synthetic cell-cell communication networks can improve our quantitative understanding of naturally occurring signaling pathways and enhance our capabilities to engineer coordinated cellular behavior in cell populations. Towards accomplishing these goals in eukaryotes, we developed and analyzed two artificial cell-cell communication systems in yeast. We integrated Arabidopsis thaliana signal synthesis and receptor components with yeast endogenous protein phosphorylation elements and new response promoters. In the first system, engineered yeast 'sender' cells synthesize the plant hormone cytokinin, which diffuses into the environment and activates a hybrid exogenous/endogenous phosphorylation signaling pathway in nearby engineered yeast 'receiver' cells. For the second system, the sender network was integrated into the receivers under positive-feedback regulation, resulting in population density-dependent gene expression (that is, quorum sensing). The combined experimental work and mathematical modeling of the systems presented here can benefit various biotechnology applications for yeast and higher level eukaryotes, including fermentation processes, biomaterial fabrication and tissue engineering.
合成细胞间通信网络的构建能够增进我们对自然发生的信号通路的定量理解,并提升我们在细胞群体中设计协调细胞行为的能力。为了在真核生物中实现这些目标,我们在酵母中开发并分析了两种人工细胞间通信系统。我们将拟南芥信号合成和受体组件与酵母内源性蛋白质磷酸化元件及新的响应启动子整合在一起。在第一个系统中,经过工程改造的酵母“发送”细胞合成植物激素细胞分裂素,该激素扩散到环境中并激活附近经过工程改造的酵母“接收”细胞中的外源/内源混合磷酸化信号通路。对于第二个系统,发送网络在正反馈调节下被整合到接收细胞中,从而导致群体密度依赖性基因表达(即群体感应)。此处展示的系统的实验工作与数学建模相结合,可使酵母和高等真核生物的各种生物技术应用受益,包括发酵过程、生物材料制造和组织工程。