Developing orthogonal synthetic signaling cascades

开发正交合成信号级联

• 批准号: DP150100936
• 负责人: Prof Kirill Alexandrov
• 金额: $ 37.06万
• 依托单位: The University of Queensland
• 依托单位国家: 澳大利亚
• 项目类别: Discovery Projects
• 财政年份: 2015
• 资助国家: 澳大利亚
• 起止时间: 2015-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://dataportal.arc.gov.au/RGS/Web/Grants/DP150100936
• 关键词: Developing; orthogonal; synthetic; signaling; cascades

This project proposes a generic approach for the construction of molecular switches based on artificially autoinhibited proteases. The bottom-up design of protein-based signaling networks is a key goal of synthetic biology. Yet, this remains elusive due to our inability to tailor-make signal transducers and receptors that can be readily compiled into defined signaling networks. Using structure-guided design and directed protein evolution, a set of protease-based signal transducers and ligand activated allosteric receptors will be created. The developed components are intended to be used to construct artificial signaling networks in mammalian cells that are orthogonal to the endogenous signaling cascades.

本计画提出一种以人工抑制蛋白酶为基础的分子开关建构的一般方法。自下而上设计基于蛋白质的信号网络是合成生物学的一个关键目标。然而，由于我们无法定制可以轻松编译成定义的信号网络的信号转换器和受体，因此这仍然难以捉摸。利用结构导向设计和定向蛋白质进化，将创建一组基于蛋白酶的信号传导器和配体激活的变构受体。开发的组件旨在用于在哺乳动物细胞中构建与内源性信号级联正交的人工信号网络。