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

计算机使用两种机制来存储数据：只读存储器(ROM)和随机存取存储器(RAM)，只读存储器可以写入但不能擦除，随机存取存储器可以多次写入和擦除。细胞也可以通过永久修改遗传密码来存储高密度只读数据，它们有可能被用作数字设备的可持续数据存储组件。然而，使用允许多个写入-读取-擦除周期的类似RAM的方法在单元中存储高密度数据仍然具有挑战性。此外，在不影响细胞活力的情况下，无中断地读出存储的生物信息的方法有限。为了克服这些挑战，该项目将把信息编码到细胞内的不同生物分子中，包括保留在细胞内的合成RNA，以及可以在细胞内外扩散的氧化还原活性小分子。在细胞外，将使用代表可持续生物材料的半导体聚合物来检测介体。所有这些组件将被组装成一个具有高存储和通信功能的生物-半导体混合系统。这项研究将培训攻读多个学科的博士生在跨学科团队中有效地工作，并将教育社区学院的学者关于研究和转移机会。这项研究的目标是创建混合细胞-材料系统，能够使用RNA在细胞中高密度存储数据(100字节)，并通过氧化还原活性化学介质的生物生产轻松读出。这些系统将通过对细胞编程以合成介体成分，通过使用简单的低能量电化学读出，并通过以最小化细胞健康负担和数据存储失败率的方式解码来自活细胞的信息来创建。将开发添加剂制造方法，以实现可扩展和可持续的生物混合系统。将使用两种新形式的生物存储元件来创建能够重复写入-读取-擦除数据周期的随机存取存储器。首先，将创建RNA存储器，使用高度可设计的催化RNA对数据进行编码。其次，将创建可以在细胞外使用半导体聚合物读出的介体存储器。概念验证生物电子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存储元件的模块化程度，以确定这些方法在不同细胞机箱中的便携性。该项目由生物科学局(BIO)的分子和细胞生物科学部(MCB)、计算机和信息科学与工程局(CEISE)的计算和通信基础部(CCF)、工程局(ENG)的电气、通信和网络系统(ECCS)共同资助，这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.