NF-kB信号通路的全新设计与合成

项目名称： NF-kB信号通路的全新设计与合成

项目编号： No.31470819

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 魏平

作者单位： 北京大学

项目金额： 80万元

中文摘要： 真核细胞进化出多种高度保守的信号转导网络，能够对环境的变化做出非常复杂的动态响应，这些动态响应在时间、空间以及数量上的差异决定着不同的细胞命运。尽管这些信号网络的单个组份已经被广泛研究，但是它们如何组织在一起形成复杂的网络结构，精确的、动态的调控生命过程，仍然是从根本上理解生命系统的关键问题。本项目将运用系统与合成生物学方法，在真核生物酵母细胞内，从头设计合成哺乳动物细胞经典NF-kB信号通路，结合理论计算，研究认识信号通路的构建原理与动力学信号调控机制，发展特定动力学功能信号网络的人工设计方法。这种以建易学的研究思路，将帮助我们深入理解信号转导网络的结构与功能的关系。揭示这类网络的设计和进化原理，不仅使我们从根本上理解与这类信号转导网络相关的疾病发生发展的机制，更将赋予我们对天然信号转导网络进行重新设计编程的能力，最终实现客户定制式的信号网络设计合成，并广泛应用到医疗和工业生产中。

中文关键词： 合成生物学；生物网络；信号传导；信号动力学；功能模块

英文摘要： The ability to sense environmental signal and make proper decisions is crucial for biology. A number of highly conserved signaling transduction kinase modules evolved to be able to deal with environmental signals with complicated response dynamics. The spatial, temporal and quantitative changes of signaling dynamics determine cell-fate, such as proliferation, differentiation, and apoptosis. Despite that the individual components of these kinase modules have been widely characterized, it is still a major challenge in biological research to fully understand how intracellular molecular components interact to form complex networks that can precisely and dynamically regulate cellular processes. We propose to combine the recent development of systems biology theory with the experimental exploration of synthetic biology approaches to design and resynthesize human nuclear factor-kappa B (NF-kB) signaling cascades in the budding yeast, to ask how to design signaling cascades with desired signaling dynamics, and how these dynamic signals regulate differential downstream gene expression. Such Learning by Building strategy could enable us to fully understand the relationship of signaling networks' structure and function. Uncovering these synthetic signaling networks' designing and evolutionary principles, would lead us to further understand the mechanism of signaling network related diseases, and also be able to reprogram natural occurring signaling transduction networks, eventually achieve the ability of the customized signaling cascades design, which could greatly benefit extensive therapeutic purpose and biological industry.

英文关键词： Synthetic biology;Signaling Networks;Signaling Transduction;Signaling Dynamics;Signaling Modules