SHF: Small: Localized DNA Hybridization Computation

SHF：小型：局部 DNA 杂交计算

• 批准号: 1320360
• 负责人: John Reif
• 金额: $ 40万
• 依托单位: Duke University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1320360&HistoricalAwards=false
• 关键词: SHF; Small; Localized; DNA; Hybridization

This project focuses on an emerging challenge in computation: to extend programmatic control over matter and phenomenon at the nanoscale. Nanosystems making use of DNA-based reactions are a promising technique to achieve this since they are feasible to design, simulate and test experimentally. DNA computation systems of increasing complexity have been demonstrated over the past two decades. Most of these systems involve multiple strands of DNA that interact with each other via diffusion based hybridization chemistry. While this paradigm has many advantages and merits, there are fundamental limits to diffusion based DNA hybridization computations, particularly due the increased time for larger-scales of complexity. This work seeks to study an alternate paradigm of DNA hybridization-based computations that operate locally on a substrate. Locality allows reactions to proceed at higher speed due to increased local concentration of reacting species - this localization could potentially speed up DNA hybridization-based computations by an order of magnitude. Also, since each of the local reaction pathways do not interfere with each other, it is also possible to simultaneously execute multiple pathways in parallel. This also allows one to reuse DNA sequences in spatially separated regions that increase the modularity and scalability of the reactions. Intellectual Merit: The research work spans both theory and experimental techniques, and includes development of biophysical mathematical models, design software, computational simulations, small-scale experimental demonstrations. In particular, the work will develop biophysical models of localized hybridization, which will be simulated, and also verified via simple kinetic experiments. The experiments provide crucial data about the rate constants involved in the hybridization chemistry of localized molecules. The simulation model will be further refined based on the experimental data,. A major challenge addressed as a center-piece of this effort is leaks: the unintended reactions that cause the nanosystem to significantly deviate from its programmed trajectory that might occur in localized hybridization systems. Multiple leak models will be tested in the lab via simple experiments. Continuing an on-going collaboration with Dr. Andrew Phillips (Microsoft Research Cambridge), funded internally by Microsoft, this work will also create software systems that will simulate localized hybridization networks. The simulation software development will be tightly coupled to the experimental progress by constantly refining the simulation models and parameters based on experimental data. Finally, this work will experimentally implement a series of small to moderate scale localized hybridization systems to demonstrate the feasibility and the potential of localized hybridization reactions. The work will also investigate the broader issues of the use of locality to speed-up other related molecular-scale computation processes, including reactions that make use of enzymes, or other protein-based reactions, in addition to DNA hybridization reactions. Broader Impact: There is substantial multidisciplinary impact to nanoscience, biochemistry and chemistry, which will profit from the introduction of key methodologies derived from mainstream computer science, such as mathematical modeling, software engineering, algorithms and modular design methodologies. Educational impact includes cross-disciplinary training of four PhD students, carefully supervised mentoring and summer internships for undergraduates.

该项目着重于计算中的新兴挑战：扩展对纳米级物质和现象的程序化控制。利用基于DNA的反应的纳米系统是实现这一目标的一种有前途的技术，因为它们可以通过实验设计，模拟和测试。在过去的二十年中，已经证明了增加复杂性的DNA计算系统。这些系统中的大多数涉及多个通过基于扩散的杂交化学相互相互作用的DNA。尽管该范式具有许多优点和优点，但基于扩散的DNA杂交计算的基本限制，尤其是由于复杂性较大尺度的时间增加。这项工作旨在研究基于基板本地运行的基于DNA杂交的计算的替代范式。局部性允许由于反应物种的局部浓度增加而以更高的速度进行反应 - 这种定位可能会通过数量级来加快基于DNA杂交的计算。同样，由于每个局部反应途径都不会彼此干扰，因此也可以同时并行执行多个途径。这还允许在空间分离的区域中重复使用DNA序列，从而增加了反应的模块化和可伸缩性。智力优点：研究工作涵盖了理论和实验技术，包括生物物理数学模型，设计软件，计算模拟，小规模的实验演示的开发。特别是，这项工作将开发出局部杂交的生物物理模型，该模型将进行模拟，并通过简单的动力学实验进行验证。这些实验提供了有关局部分子杂交化学涉及的速率常数的关键数据。模拟模型将根据实验数据进一步完善。作为这项工作中心的一个重大挑战是泄漏：导致纳米系统明显偏离其程序性轨迹的意外反应，可能发生在局部杂交系统中。将通过简单的实验在实验室中测试多个泄漏模型。这项工作继续与Microsoft内部资助的Andrew Phillips（Microsoft Research Cambridge）进行持续的合作，还将创建软件系统，以模拟局部杂交网络。通过根据实验数据不断完善模拟模型和参数，模拟软件开发将与实验进度紧密耦合。最后，这项工作将在实验中实施一系列小到中等规模的局部杂交系统，以证明局部杂交反应的可行性和潜力。这项工作还将调查使用局部性来加速其他相关分子规模计算过程的更广泛问题，包括使用酶的反应或其他基于蛋白质的反应的反应，除了DNA杂交反应外。更广泛的影响：对纳米科学，生物化学和化学有实质性的多学科影响，这将从引入源自主流计算机科学的关键方法中获利，例如数学建模，软件工程，算法和模块化设计方法。教育影响包括对四名博士学位学生的跨学科培训，精心监督的指导以及针对本科生的暑期实习。