Sentinels: A plug-and-play RNA sensing technology platform for surveillance and response to emerging viral diseases

Sentinels：即插即用的 RNA 传感技术平台，用于监测和应对新出现的病毒性疾病

• 批准号: 2128370
• 负责人: James Chappell
• 金额: $ 67.39万
• 依托单位: William Marsh Rice University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2128370&HistoricalAwards=false
• 关键词: Sentinels; plug; play; RNA; sensing

Cells can be programmed to sense infectious agents and, in response, actuate biomolecular programs to alert, protect the host, or destroy the pathogenic target. Engineering cells in this manner would provide a transformative approach to address the threat of emerging viral diseases. The goal of this project is to develop a novel pathogen detection platform that can be easily reprogrammed to sense new threats, and in response, produce any protein output. This technology will forward our ability to engineer sentinel cells for diverse diagnostics and therapeutic applications. This project will also provide educational and training opportunities aimed at increasing the number and diversity of high school students and undergraduates pursuing careers in biomolecular and cellular engineering, and related STEM fields. As part of this project open-source web-based design tools for designing sentinel cells will be created through a student-led initiative.RNA-based sensors present a particularly attractive option for programming cells to detect pathogens because they rely on designable RNA base pairing interactions and enable detection of RNA encoded genomes (genotypes) and mRNAs (phenotypes) of both the pathogen and host, allowing for potentially more accurate readouts of the infection status. However, there is currently a lack of genetically-encoded RNA detection platforms that can interface RNA inputs to biomolecular outputs, precluding the design of cellular devices that execute sentinel programs in response to specific RNA signatures. To address this, biomolecular and synthetic biology strategies to create plug-and-play RNA sense-and-respond platforms will be explored. Devices will be created that detect different virus associated RNA molecules, and, in response, activate diverse biomolecular programs to alert and destroy viruses. This will find direct applications for sentinel cell design and could be easily utilized for other applications in basic science, synthetic biology, and metabolic engineering.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.

细胞可以被编程来感知感染因子，并作为响应启动生物分子程序来警报、保护宿主或破坏致病目标。以这种方式改造细胞将为解决新出现的病毒性疾病的威胁提供一种变革性的方法。该项目的目标是开发一种新型病原体检测平台，该平台可以轻松地重新编程以感知新的威胁，并作为响应产生任何蛋白质输出。这项技术将提高我们设计前哨细胞以用于各种诊断和治疗应用的能力。该项目还将提供教育和培训机会，旨在增加从事生物分子和细胞工程以及相关 STEM 领域职业的高中生和本科生的数量和多样性。作为该项目的一部分，将通过学生主导的项目创建用于设计前哨细胞的开源网络设计工具。基于 RNA 的传感器为编程细胞检测病原体提供了一个特别有吸引力的选择，因为它们依赖于可设计的 RNA 碱基配对相互作用并能够检测病原体和宿主的 RNA 编码基因组（基因型）和 mRNA（表型），从而可以更准确地读出感染状态。然而，目前缺乏能够将 RNA 输入与生物分子输出连接起来的基因编码 RNA 检测平台，从而阻碍了执行响应特定 RNA 特征的哨兵程序的细胞设备的设计。为了解决这个问题，将探索生物分子和合成生物学策略来创建即插即用的 RNA 感知和响应平台。将创建检测不同病毒相关 RNA 分子的设备，并作为响应激活不同的生物分子程序来警报和消灭病毒。这将为前哨细胞设计找到直接应用，并可轻松用于基础科学、合成生物学和代谢工程中的其他应用。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力优势和更广泛的评估进行评估，被认为值得支持。影响审查标准。