Collaborative Research: FET: Medium: Engineering DNA and RNA computation through simulation, sequence design, and experimental verification

合作研究：FET：中：通过模拟、序列设计和实验验证进行 DNA 和 RNA 计算

• 批准号: 2211793
• 负责人: David Doty
• 金额: $ 38万
• 依托单位: University of California-Davis
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2211793&HistoricalAwards=false
• 关键词: Collaborative; Research; FET; Medium; Engineering

Designed nucleic acid sequences (DNA or RNA) can self-assemble into nanoscale structures and devices with promising applications in diagnostics, therapeutics, and nanoscale manufacturing. Strand displacement, where an invader single strand displaces an incumbent strand bound to a complementary substrate, is a key process in dynamic DNA nanotechnology. While DNA strand displacement circuits have proven to be capable of complex computation, they do not interface as naturally to biological systems (e.g., CRISPR) as RNA. Meanwhile, RNA circuits have not achieved the same level of success. This research aims to develop a richer understanding and precise control of hybrid DNA:RNA displacement that may lead to entirely new levels of sophistication in molecular circuits capable of inter-operation with biological systems. A flexible, user-friendly sequence design tool will significantly reduce the barrier to implementation for non-experts. Education and outreach activities will broaden participation in computing and cross-train students in multiple disciplines by reaching across subject boundaries. The investigators will collect experimental data to parameterize new coarse-grained models of DNA-RNA hybrid systems, including Markov chain models capable of rapid in-silico simulation to determine kinetic reaction rates. These hybrid models will also parameterize mismatch creation and repair during displacement making possible the design of strand displacement reactions with precise kinetic control using both DNA and RNA, and thus allowing a natural interface of complex computational cascades with biological signals. A general-purpose DNA and RNA sequence design tool will be developed that focuses on four tasks: algorithmic/efficiency improvements, development of new models to enhance the behaviors expressible as constraints, integration with existing tools, and the design and experimental demonstration of a hybrid DNA:RNA displacement system that implements a self-stabilizing clock, capable of producing RNA strands at a fixed period.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.

设计的核酸序列（DNA 或 RNA）可以自组装成纳米级结构和器件，在诊断、治疗和纳米级制造方面具有广阔的应用前景。链置换，即入侵单链置换与互补底物结合的现有链，是动态 DNA 纳米技术的关键过程。 虽然 DNA 链置换电路已被证明能够进行复杂的计算，但它们不像 RNA 那样自然地与生物系统（例如 CRISPR）连接。与此同时，RNA 回路还没有取得同样程度的成功。 这项研究旨在更丰富地理解和精确控制杂交 DNA:RNA 位移，这可能导致能够与生物系统互操作的分子电路的复杂程度达到全新水平。 灵活、用户友好的序列设计工具将显着降低非专家的实施障碍。 教育和推广活动将扩大对计算机的参与，并通过跨越学科界限对多个学科的学生进行交叉培训。研究人员将收集实验数据来参数化 DNA-RNA 混合系统的新粗粒度模型，包括能够快速进行计算机模拟以确定动力学反应速率的马尔可夫链模型。这些混合模型还将参数化置换过程中的错配产生和修复，使得使用 DNA 和 RNA 进行精确动力学控制的链置换反应设计成为可能，从而允许复杂计算级联与生物信号的自然界面。将开发通用 DNA 和 RNA 序列设计工具，重点关注四项任务：算法/效率改进、开发新模型以增强可表达为约束的行为、与现有工具集成以及混合模型的设计和实验演示DNA:RNA 置换系统，实现自稳定时钟，能够在固定周期产生 RNA 链。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Proceedings of the 29th International Conference on DNA Computing and Molecular Programming (DNA 29)

第 29 届国际 DNA 计算和分子编程会议论文集 (DNA 29)

• DOI: 10.4230/lipics.dna.29.8
• 发表时间: 2023-01
• 期刊: Schloss Dagstuhl – Leibniz-Zentrum für Informatik
• 作者: Petrack, Joshua;Soloveichik, David;Doty, David
• 通讯作者: Doty, David

Rate-independent Computation in Continuous Chemical Reaction Networks

连续化学反应网络中的速率无关计算

• DOI: 10.1145/3590776
• 发表时间: 2023-06
• 期刊: Journal of the ACM
• 影响因子: 2.5
• 作者: Chen, Ho;Doty, David;Reeves, Wyatt;Soloveichik, David
• 通讯作者: Soloveichik, David

Proceedings of the 29th International Conference on DNA Computing and Molecular Programming (DNA 29)

第 29 届国际 DNA 计算和分子编程会议论文集 (DNA 29)

• DOI: 10.4230/lipics.dna.29.9
• 发表时间: 2023-01
• 期刊: Schloss Dagstuhl – Leibniz-Zentrum für Informatik
• 作者: Luchsinger, Austin;Doty, David;Soloveichik, David
• 通讯作者: Soloveichik, David