Noncoding RNA based platforms for in vivo biosensors

基于非编码 RNA 的体内生物传感器平台

• 批准号: 7155755
• 负责人: KEVIN G HOFF
• 金额: $ 5.04万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7155755
• 关键词: Saccharomyces cerevisiae; biological signal transduction; biomedical equipment development; biosensor device; biotechnology; fluorescence resonance energy transfer; fungal proteins; gene expression; gene induction /repression; genetic regulation; genetic regulatory element; high throughput technology; intracellular; ligands; metabolism; mitogen activated protein kinase; molecular dynamics; nanotechnology; postdoctoral investigator; ribozymes; small interfering RNA; small molecule

DESCRIPTION (provided by applicant): In vivo monitoring of cellular signaling and metabolite flux is an essential tool to study the dynamics of cellular networks and the effects of re-engineering these networks. The aims of this proposal are the development and use of a modular, tunable, allosterically controlled biosensor platform that can simultaneously monitor and re-engineer cellular pathways. Small, noncoding RNA molecules (allosteric ribozymes, riboswitches and antiswitches) will be the basis of these biosensors and will be developed to control a fluorescent resonant energy transfer event in response to small molecule ligands or cellular signalling events. In addition, sensor components will be engineered to allow for simultaneous control of expression of endogenous cellular transcripts. A mitogen activated protein kinase pathway from S. cerevisiae will serve as a model system for biosensor development, adaptation, and translational control. These studies are predicted to establish a biosensor platform with rapid detection kinetics that is easily evolvable, modular, and capable of allosteric control of mRNA expression.

描述（由申请人提供）：细胞信号传导和代谢物通量的体内监测是研究细胞网络动力学以及重新设计这些网络的效果的重要工具。该提案的目的是开发和使用模块化，可调，变构控制的生物传感器平台，该平台可以同时监视和重新设计细胞途径。小的，非编码的RNA分子（变构核酶，核糖开关和反开关）将是这些生物传感器的基础，并将开发以控制荧光共振能量转移事件，以响应小分子配体或细胞信号事件。此外，将设计传感器组件以同时控制内源性细胞转录本的表达。酿酒酵母的有丝分裂原活化的蛋白激酶途径将作为生物传感器开发，适应和转化控制的模型系统。预计这些研究将建立具有快速检测动力学的生物传感器平台，该平台易于转化，模块化且能够对mRNA表达的变构控制。