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非线性网络控制在合成基因网络上的实验实现

已有 2377 次阅读 2017-3-11 07:46 |个人分类:科研笔记|系统分类:科研笔记| 合成生物学, 网络控制, 多稳态控制

今天刚刚收到邮件,一个做了四年的工作被elife 接收了。我们利用合成基因网络上实现了一个多稳态的系统,并利用顺序诱导的方法实现了多稳态共存。这个平台实际上是我们之前Nature Comm的实验实现和验证。



Engineeringof a synthetic quadrastable gene network to approach Waddington landscape andcell fate determination

Fuqing Wu,1 Ri-QiSu,1,2Ying-Cheng Lai,2,3,4 XiaoWang1*

Abstract

The process of cell fatedetermination has been depicted intuitively as cells travelling and resting ona rugged landscape, which has been probed by various theoretical studies.However, few studies have experimentally demonstrated how underlying gene regulatorynetworks shape the landscape and hence orchestrate cellular decision-making inthe presence of both signal and noise. Here we tested different topologies andverified a synthetic gene circuit with mutual inhibition and auto-activationsto be quadrastable, which enables direct study of quadruple cell fatedetermination on an engineered landscape. We show that cells indeed gravitatetowards local minima and signal inductions dictate cell fates throughmodulating the shape of the multistable landscape. Experiments, guided by modelpredictions, reveal that sequential inductions generate distinct cell fates bychanging landscape in sequence and hence navigating cells to different finalstates. This work provides a synthetic biology framework to approach cell fatedetermination and suggests a landscape-based explanation of fixed inductionsequences for targeted differentiation.  

Keywords   synthetic gene network; quadrastability; cellfate programming; sequential induction; Waddington landscape




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