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（Watson）和克里克（Crick）首先描述了DNA的分子结构以来，其信息的潜力对计算机科学家显而易见。序列中的每个核苷酸都从A，T，C和G的四值字母中绘制，它的DNA分子具有N核苷酸的4个位于数据n位的功率。原则上，DNA可以提供比常规培养基比传统培养基更密集的储存介质。在生物技术和制药行业的刺激下，测序（阅读）和合成（写作）DNA的技术迅速发展。然而，从理论上的阅读/写作速度和实践中证明的内容方面，理论上可能的东西之间仍然存在很大的差距。这项研究的工业合作伙伴Seagate正在开发一个电子平台来缩小差距。学术团队的目标是探索Seagate正在开发的技术的替代应用。这些范围从对DNA中存储的数据进行计算的新颖方式到操纵合成细胞，到工程生物反应器。在整个过程中，学术团队将努力进行高水平的公众参与。计划的活动包括启动政策讨论，特别是关于人造生活和生物安全的讨论，以及吸引高中生的生物化学“制造商”文化。该建议与基于数字微流体学的DNA存储的最新系统有关。这样的技术通过电荷在网格上操纵小滴。电子设备执行各种复杂操作来组装DNA：合并，分裂，加热，冷却，混合和净化。学术团队将探索一种计算存储的数据的方案，而不是以DNA的核苷酸序列，而是在对链的拓扑修改中：DNA的磷酸化酯主链中断裂，称为“ nicks”，差距称为“ toeholds”。在先前的工作中，通过用CRISPR/CAS9等酶促系统划分DNA来证明这种计算。在这项工作中，带有必要的划痕和脚趾的DNA将直接组装在电子网格上。学术团队还将探索合成生物学中的应用，包括无细胞的蛋白质表达，脂质体封装和直接在电子电网上的RNA工程。该项目由生物科学局（BIO）的分子和细胞生物科学（MCB）共同资助；计算机和信息科学与工程局（CISE）的计算与通信基金会（CCF）司；电气，通信和网络系统（ECC）在工程局（ENG）和材料研究局（DMR）局（DMR）局（MPS）（MPS）（MPS）。本奖反映了NSF的法定任务，并通过基金会的知识分子优点和广泛的影响来评估NSF的法定任务，并被视为值得通过评估的支持。