Bio-QuBIC: Designer Gene Networks for Biocomputing Applications

Bio-QuBIC：用于生物计算应用的设计基因网络

• 批准号: 0130331
• 负责人: James Collins
• 金额: $ 50万
• 依托单位: Trustees of Boston University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-15 至 2005-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0130331&HistoricalAwards=false
• 关键词: Bio; QuBIC; Designer; Gene; Networks

EIA-0130331James.J. CollinsBoston UniversityTitle: Designer Gene Networks for Biocomputing ApplicationsMany fundamental cellular processes are governed by genetic networks which employ protein-DNA interactions in regulating function. The biochemistry of the feedback loops associated with protein-DNA interactions leads to nonlinear effects, and the tools of nonlinear analysis become invaluable. This project involves the use of techniques from nonlinear dynamics and molecular biology to model, design and construct synthetic gene networks for biocomputing applications. Here biocomputing is defined as representing the ability of cells to make decisions based on external stimuli, and in this context, synthetic gene networks can be viewed as "controllers" for living cells. In this project, a rapidly switching genetic toggle switch is being modeled and constructed in bacterial cells. The genetic toggle switch, which is a fundamental unit of biocomputing memory storage, can be flipped between two stable expression states using transient chemical or thermal stimuli. In addition, as part of this project, synthetic gene networks based on more complicated logic gates (i.e., AND and OR gates) are being designed, modeled and constructed in bacterial cells. These circuits can function as sensors of multiple transient signals, and form the basis for general control schemes requiring an "if/then" structure.Synthetic gene networks represent a first step towards logical cellular control, whereby biological processes can be manipulated or monitored at the DNA level. Ultimately, synthetic gene circuits encoded into DNA, might be "downloaded" into cells creating, in effect, a "wet" nano-robot. These cellular robots could be utilized for a variety of functions, including in vivo biosensing, autonomously synthesizing complex biomaterials, executing programmed cell death, and interfacing with microelectronic circuits by transducing biochemical events to and from the electronics.

生物计算应用的设计者基因网络许多基本的细胞过程是由基因网络控制的，基因网络利用蛋白质-DNA相互作用来调节功能。与蛋白质-DNA相互作用相关的反馈回路的生物化学导致非线性效应，非线性分析工具变得非常宝贵。该项目涉及使用非线性动力学和分子生物学技术来建模，设计和构建用于生物计算应用的合成基因网络。 在这里，生物计算被定义为代表细胞根据外部刺激做出决定的能力，在这种情况下，合成基因网络可以被视为活细胞的“控制器”。 在这个项目中，一个快速切换的遗传拨动开关正在细菌细胞中建模和构建。 遗传切换开关是生物计算记忆存储的基本单元，可以使用瞬时化学或热刺激在两个稳定表达状态之间翻转。 此外，作为该项目的一部分，基于更复杂逻辑门的合成基因网络（即，AND和OR门）正在细菌细胞中设计、建模和构建。 这些电路可以作为多个瞬态信号的传感器，并形成需要“如果/那么”结构的一般控制方案的基础。合成基因网络代表了逻辑细胞控制的第一步，从而可以在DNA水平上操纵或监测生物过程。最终，编码到DNA中的合成基因电路可能会被“下载”到细胞中，从而产生一个“湿”纳米机器人。 这些细胞机器人可以用于各种功能，包括体内生物传感，自主合成复杂的生物材料，执行程序化细胞死亡，以及通过将生化事件转换到电子设备和从电子设备转换来与微电子电路接口。