AF: SHF: Small: Adaptive molecular computation using buffered strand displacement networks

AF：SHF：小：使用缓冲链位移网络的自适应分子计算

• 批准号: 1525553
• 负责人: Matthew Lakin
• 金额: $ 45万
• 依托单位: University of New Mexico
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1525553&HistoricalAwards=false
• 关键词: AF; SHF; Small; Adaptive; molecular

Learning and adaptation are fundamental processes in living systems. Human beings are clearly capable of learning complex concepts, but even unicellular organisms such as bacteria are capable of adaptive response to external stimuli. This suggests that synthetic systems of biomolecules could, in principle, be developed to enable sustained operation and exhibit similar adaptive behaviors. Thanks to advances in the tools developed in the fields of biotechnology and nanotechnology, it is now becoming possible to engineer such systems in the laboratory. This project will study the design and experimental implementation of synthetic DNA-based information processing systems that exhibit adaptive behaviors such as learning. Successful completion of this research will enable future development of synthetic biochemical systems capable of sustained operation, which could have practical applications such as long-term health monitoring, as well as providing insights into the biochemical basis of learning in biological systems. The project will support training and education of undergraduate and graduate students.This project will study learning and adaptation in synthetic biochemical systems implemented using DNA strand displacement reactions. In DNA strand displacement reaction networks, multi-strand DNA "gate" structures are used to process information that is encoded using single strands of DNA, by binding to freely-diffusing single strands and releasing other single strands into solution in response. In this project, a particular class of DNA strand displacement gates known as "buffered gates" will be developed. A buffered gate is one where a large quantity of gates start in an inactive state and a subset are activated to carry out their computational task: once each gate is consumed, in addition to its usual outputs the gate also releases a strand to activate a new gate from the buffer, so the population of active gates remains roughly constant. In this project, buffered gate systems will be studied in simulation and in the laboratory. Crucially, buffered gate systems in which one gate controls the availability of activating strands for another buffered gate will be studied. This will enable information to be stored and updated with the molecular system, thereby enabling adaptive behavior. This concept will be used as the fundamental design building block to implement molecular computing systems capable of adaptive behavior in response to externally-provided input signals. The goal of this project will be to design, simulate and implement molecular logic systems that demonstrate adaptive behavior, for example, implementing supervised learning algorithms.

学习和适应是生活系统中的基本过程。人类显然能够学习复杂的概念，但是即使是细菌的单细胞生物也能够适应对外部刺激的反应。这表明，原则上可以开发生物分子的合成系统来实现持续的运行并表现出相似的适应性行为。得益于在生物技术和纳米技术领域开发的工具的进步，现在在实验室中设计这种系统正成为可能。该项目将研究基于合成DNA的信息处理系统的设计和实验实施，这些信息处理系统表现出适应性行为，例如学习。这项研究的成功完成将使能够持续运行的合成生化系统的未来开发，这可能具有长期健康监测等实际应用，并提供对生物系统学习生化基础的见解。该项目将支持本科和研究生的培训和教育。该项目将研究使用DNA链置换反应实施的合成生化系统的学习和适应。在DNA链位移反应网络中，多链DNA“栅极”结构用于处理使用DNA的单链编码的信息，通过与自由凹入的单链结合并将其他单个链释放到溶液中以响应。在这个项目中，将开发一类特定的DNA链位移门被称为“缓冲门”。缓冲门是一个以不活动状态开始的大量门开始，并激活一个子集以执行其计算任务：一旦消耗了每个门，除了其通常的输出外，该栅极还释放了一条链以从缓冲区中激活一个新的门，因此活动门的数量保持了大致恒定。在该项目中，将在模拟和实验室中研究缓冲的门系统。至关重要的是，将研究一个栅极控制另一个缓冲栅极的激活链的可用性的缓冲门系统。这将使信息能够通过分子系统存储和更新，从而实现适应性行为。该概念将用作实施能够响应外部提供的输入信号来实现能够自适应行为的分子计算系统的基本设计构建块。该项目的目的是设计，模拟和实施分子逻辑系统，以表明适应性行为，例如实施监督的学习算法。

项目成果

Robust Heterochiral Strand Displacement Using Leakless Translators

• DOI: 10.1021/acssynbio.0c00131
• 发表时间: 2020-07-17
• 期刊: ACS SYNTHETIC BIOLOGY
• 影响因子: 4.7
• 作者: Mallette, Tracy L.;Stojanovic, Milan N.;Lakin, Matthew R.
• 通讯作者: Lakin, Matthew R.

Microcompartments for Protection and Isolation of Nanoscale DNA Computing Elements

• DOI: 10.1021/acsami.9b03143
• 发表时间: 2019-03-27
• 期刊: ACS APPLIED MATERIALS & INTERFACES
• 影响因子: 9.5
• 作者: Fahry-Wood，Aurora;Fetrow，Madalyn Elise;Lakin，Matthew R.
• 通讯作者: Lakin，Matthew R.

Domain-Specific Programming Languages for Computational Nucleic Acid Systems

• DOI: 10.1021/acssynbio.0c00050
• 发表时间: 2020-07-17
• 期刊: ACS SYNTHETIC BIOLOGY
• 影响因子: 4.7
• 作者: Lakin, Matthew R.;Phillips, Andrew
• 通讯作者: Phillips, Andrew

Automated analysis of tethered DNA nanostructures using constraint solving

• DOI: 10.1007/s11047-018-9693-y
• 发表时间: 2018-12-01
• 期刊: NATURAL COMPUTING
• 影响因子: 2.1
• 作者: Lakin, Matthew R.;Phillips, Andrew
• 通讯作者: Phillips, Andrew

A Logic Programming Language for Computational Nucleic Acid Devices

• DOI: 10.1021/acssynbio.8b00229
• 发表时间: 2019-07-01
• 期刊: ACS SYNTHETIC BIOLOGY
• 影响因子: 4.7
• 作者: Spaccasassi, Carlo;Lakin, Matthew R.;Phillips, Andrew
• 通讯作者: Phillips, Andrew