GOALI: SemiSynBio-III: Moving Millions of Droplets at Megahertz Speeds: DNA Computing, DNA Storage, and Synthetic Biology on an Industrial Platform for Digital Microfluidics

目标：SemiSynBio-III：以兆赫兹速度移动数百万个液滴：数字微流体工业平台上的 DNA 计算、DNA 存储和合成生物学

• 批准号: 2227578
• 负责人: Marc Riedel
• 金额: $ 100万
• 依托单位: University of Minnesota-Twin Cities
• 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: 2022-10-01 至 2025-09-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2227578&HistoricalAwards=false
• 关键词: GOALI; SemiSynBio; III; Moving; Millions

Ever since Watson and Crick first described the molecular structure of DNA, its information-bearing potential has been apparent to computer scientists. With each nucleotide in the sequence drawn from the four-valued alphabet of A, T, C, and G, a molecule of DNA with n nucleotides stores 4 to the power of n bits of data. In principle, DNA could provide a storage medium that is many orders of magnitude denser than conventional media. Spurred by the biotech and pharma industries, the technology for both sequencing (reading) and synthesizing (writing) DNA has progressed rapidly. Nevertheless, a large gap remains between what is theoretically possible in terms of reading/writing speed and what has been demonstrated in practice. The industrial partner in this research, Seagate, is developing an electronic platform to close the gap. The goal of the academic team is to explore alternate applications of the technology that Seagate is developing. These range from novel ways of performing computation on data stored in DNA, to manipulating synthetic cells, to engineering bioreactors. Throughout, the academic team will strive for a high level of public engagement. Planned activities include initiating policy discussions, particularly regarding artificial life and biosafety, and engaging high-school students in biochem "maker" culture. This proposal pertains to a state-of-the-art system for DNA storage based on digital microfluidics. Such technology manipulates small droplets on a grid via electric charge. The electronics perform a variety of complex operations to assemble DNA: merging, splitting, heating, cooling, mixing, and purifying. The academic team will explore a scheme for computing on data stored not in the sequence of nucleotides of the DNA but rather in topological modifications to the strands: breaks in the phosphodiester backbone of DNA called "nicks" and gaps called "toeholds". In prior work, such computation has been demonstrated by nicking DNA with enzymatic systems such as CRISPR/Cas9. In this work, DNA with the requisite nicks and toeholds will be assembled directly on the electronic grid. The academic team will also explore applications in synthetic biology, including cell-free protein expression, liposome encapsulation, and RNA engineering directly on the electronic grid. The project was jointly funded by the 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.

自从沃森和克里克首次描述DNA的分子结构以来，它承载信息的潜力对计算机科学家来说是显而易见的。从A、T、C和G四个字母中提取序列中的每个核苷酸，一个含有n个核苷酸的DNA分子存储4的n次方位数据。原则上，DNA可以提供比传统介质密度大许多数量级的存储介质。在生物技术和制药行业的推动下，DNA测序（读取）和合成（写入）技术发展迅速。然而，在理论上可能的读/写速度和实践中已经证明的速度之间仍然存在很大的差距。这项研究的工业合作伙伴希捷公司正在开发一种电子平台来缩小差距。学术团队的目标是探索希捷正在开发的技术的替代应用。从对存储在DNA中的数据进行计算的新方法，到操纵合成细胞，再到工程生物反应器。在整个过程中，学术团队将努力争取高水平的公众参与。计划中的活动包括启动政策讨论，特别是关于人工生命和生物安全的政策讨论，以及让高中生参与生物化学“创客”文化。这是一种基于数字微流体技术的DNA存储系统。这种技术通过电荷操纵网格上的小液滴。电子设备执行各种复杂的操作来组装DNA：合并、分裂、加热、冷却、混合和纯化。该学术团队将探索一种方案，以计算存储在DNA的核苷酸序列中，而不是存储在链的拓扑修饰中的数据：DNA磷酸二酯主链中的断裂称为“缺口”，间隙称为“支点”。在之前的工作中，这种计算已经通过使用CRISPR/Cas9等酶系统切割DNA来证明。在这项工作中，具有必要刻痕和支点的DNA将直接在电子网格上组装。学术团队还将探索合成生物学的应用，包括无细胞蛋白表达、脂质体封装和直接在电子网格上进行RNA工程。该项目由生物科学理事会分子和细胞生物科学司（MCB）共同资助；计算机与信息科学与工程理事会（CISE）计算与通信基础处；工程理事会（ENG）的电气、通信和网络系统司（ECCS）和数学和物理科学理事会（MPS）的材料研究司（DMR）。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。