SemiSynBio-III: Hybrid cell-semiconducting polymer systems that decode cytosolic information using RNA-regulated electron transfer

SemiSynBio-III：混合细胞半导体聚合物系统，利用 RNA 调节的电子转移解码胞质信息

• 批准号: 2227526
• 负责人: Jonathan Silberg
• 金额: $ 150万
• 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: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2025-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2227526&HistoricalAwards=false
• 关键词: SemiSynBio; III; Hybrid; cell; semiconducting

Computers use two mechanisms to store data: read-only memory (ROM), which can be written but not erased, and random-access memory (RAM), which can be written and erased multiple times. Cells can also be programmed to store high density read-only data by permanently modifying the genetic code, and they have the potential to be used as sustainable data storage components for digital devices. However, it remains challenging to store high density data in cells using RAM-like approaches that allow for multiple write-read-erase cycles. In addition, there are limited methods to read out stored biological information non-disruptively, without affecting cell viability. To overcome these challenges, this project will code information into different biomolecules within cells, including synthetic RNA, which are retained within cells, and redox-active small molecules, which can diffuse in and out of cells. Outside of cells, the mediators will be detected using semiconducting polymers which represent sustainable bio-materials. All of these components will be assembled to build a hybrid biological-semiconductor system with high storage and communication functionalities. This research will train doctoral students pursuing studies in multiple disciplines to work effectively in interdisciplinary teams, and it will educate scholars at community colleges about research and transfer opportunities. The goal of this research is to create hybrid cell-material systems capable of high-density data storage in cells (100 bytes) using RNA, with facile read out through the bio-production of redox-active chemical mediators. These systems will be created by programming cells to synthesize mediator components, by using a facile low energy electrochemical read out, and by decoding information from living cells in a manner that minimizes cell fitness burdens and data storage failure rates. Additive manufacturing approaches will be developed to achieve scalable and sustainable biohybrid systems. Two novel forms of biological memory elements will be used to create random-access memory that is capable of repetitive write-read-erase data cycles. First, RNA memory will be created that codes data using a highly designable catalytic RNA. Second, mediator memory will be created that can be read out using a semiconductive polymer outside of cells. The proof-of-concept bioelectronic system will be created using the model microbe Escherichia coli. The modularity of the memory elements will then be evaluated in other gram-negative microbes to establish how portable these approaches are across different cellular chassis.This project has been jointly funded by Division of Molecular and Cellular Biosciences (MCB) in the Directorate for Biological Sciences (BIO), Division of Computing and Communication Foundations (CCF) in the Directorate for Computer and Information Science and Engineering (CISE), Division of Electrical, Communications and Cyber Systems (ECCS) in the Directorate for Engineering (ENG), and the Division of Materials Research (DMR) in the Directorate for Mathematical and Physical Sciences (MPS).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.

计算机使用两种机制来存储数据：只读内存（ROM），可以编写但不删除，而随机访问记忆（RAM）可以多次编写和删除。还可以通过永久修改遗传密码来编程细胞以存储高密度读取数据，并且它们有可能用作数字设备的可持续数据存储组件。但是，使用类似RAM的方法将高密度数据存储在单元格中仍然具有挑战性，从而可以进行多种写入读取式循环。此外，没有影响细胞活力的不间断地读取存储的生物学信息的方法有限。为了克服这些挑战，该项目将对细胞内的不同生物分子进行编码，包括保留在细胞内的合成RNA，以及可以扩散在细胞中的氧化还原活性小分子。在细胞之外，将使用代表可持续生物材料的半导体聚合物检测介体。所有这些组件都将组装，以构建具有高存储和通信功能的混合生物学系统。这项研究将培训博士生在多个学科中学习的学生，以有效地在跨学科团队中工作，并将在社区大学教育学者有关研究和转移机会的教育。这项研究的目的是创建能够使用RNA在细胞（100个字节）中进行高密度数据存储的混合细胞材料系统，并通过生物产生氧化还原活性化学介质的生产来读取。这些系统将通过编程单元格，通过使用轻松的低能电化学读取以及以最小化细胞健身负担和数据存储故障率的方式来综合介体组件来创建这些系统。将开发增材制造方法以实现可扩展和可持续的生物杂化系统。两种新型的生物记忆元素形式将用于创建能够重复的写入式启动数据周期的随机记忆。首先，将创建RNA存储器使用高度可设计的催化RNA代码数据。其次，将创建介体存储器，可以使用细胞外的半导体聚合物读取。概念验证的生物电机系统将使用模型微生物大肠杆菌创建。然后，将在其他革兰氏阴性微生物中评估记忆元件的模块化，以确定这些方法如何在不同的细胞底盘范围内进行。该项目已通过分子和细胞生物科学（MCB）在生物科学局的分子和细胞生物科学（MCB）共同资助。 （BIO），计算机和信息科学与工程局（CISE）的计算和通信基金会（CCF），电气，通信和网络系统（ECCS）的工程局（ENG）和部门的电气，通信和网络系统（ECC）材料研究（DMR）在数学和物理科学局（MPS）中。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛影响的评估标准通过评估来支持的。