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Engineering Advanced Logical Operations for Gene Control

基因控制的工程高级逻辑运算

基本信息

批准号：
1804639
负责人：
Corey Wilson
金额：
$ 33.38万
依托单位：
Georgia Tech Research Corporation
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2022-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1804639&HistoricalAwards=false
关键词：
Engineering Advanced Logical Operations Gene

项目摘要

Living systems respond to stimuli in the environment. Personalized medicine and bio-industrial applications are made possible by this trait. An obstacle to developing these applications is a lack of regulators (i.e., switches that can turn genes on or off) that can facilitate complex operations. This project will attempt to create a new class of gene regulators that can perform fundamental logical operations (i.e., AND, OR, NOT). These regulators can be combined in sequences that mimic a computer program. These biological programs will direct the cell to fulfill specific functions. One example might be the following: if compounds E (AND) F are detected, then turn on gene G; if E (OR) F are present individually, then NOT G. This project will be complemented by outreach activities aimed at educating students from underrepresented groups in state-of-the-art biological engineering. This initiative will contribute to the development of a diverse engaged science and engineering workforce, building a firm foundation for a lifetime of contributions to research, education and their integration. The goal of this project is to develop combinational logic gates (programs) in cells to implement multiple input signal control over gene transcription. The biological programming envisioned will require the creation of a new class of DNA-binding transcription factors. Successful completion of the project will result in a new class of orthogonal and modular DNA-binding transcription factors that work as logical systems. The resulting system will allow programmable microbial decision making, where different combinations of signal inputs result in distinctive combinations of genetic outputs. These transcription factors can be directly introduced into existing genetic circuits at any position where transcription is regulated by a DNA binding protein (or system of transcription factors). Successful completion of this project will result in a significant enhancement in biological computing capacity, which will enable the construction of synthetic regulatory networks at the scale of natural networks in bacteria.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

生命系统对环境中的刺激作出反应。个性化的医疗和生物工业应用是可能的，这一特点。开发这些应用的障碍是缺乏监管机构（即，可以打开或关闭基因的开关），可以促进复杂的操作。该项目将试图创建一类新的基因调节器，可以执行基本的逻辑操作（即，AND，OR，NOT）。这些调节器可以按照模拟计算机程序的顺序组合。这些生物程序将指导细胞完成特定的功能。例如：如果检测到化合物E（AND）F，则开启基因G;如果单独存在E（OR）F，则不开启基因G。这一项目将辅之以外联活动，旨在教育代表性不足群体的学生掌握最先进的生物工程。这一举措将有助于发展一支多元化的科学和工程队伍，为终身为研究、教育及其整合做出贡献奠定坚实的基础。本计画的目标是在细胞中发展组合逻辑闸（程式），以实现基因转录的多重输入讯号控制。设想的生物编程将需要创建一类新的DNA结合转录因子。该项目的成功完成将导致一类新的正交和模块化的DNA结合转录因子，作为逻辑系统工作。由此产生的系统将允许可编程的微生物决策，其中信号输入的不同组合导致遗传输出的独特组合。这些转录因子可以直接引入到现有的遗传电路中的任何位置，其中转录由DNA结合蛋白（或转录因子系统）调节。该项目的成功完成将导致生物计算能力的显著增强，这将使细菌天然网络规模的合成监管网络的构建成为可能。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。