Advancing theory and tools for molecular programming

推进分子编程的理论和工具

• 批准号: RGPIN-2016-04240
• 负责人: Condon, Anne
• 金额: $ 3.35万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=647983
• 关键词: Advancing; theory; tools; molecular; programming

Molecular programming is the process of designing information-carrying molecules that react, or execute instructions, in purposeful ways. Nucleic acids - DNA and RNA molecules - are interesting to program because of their digital sequences and dynamic structural properties, and because they extend the reach of computational devices by naturally interacting with "wet" biological systems. Researchers in the field of molecular programming are tackling exciting engineering challenges such as building logic circuits, nanoscale structures and even molecular walking robots, from DNA and RNA sequences. In the coming decades, these technologies can offer significant payoffs, in transforming the ways in which we monitor and mediate molecular dynamics within the cell, or in developing "smart drugs" that could assess concentrations of disease indicators and respond accordingly.******My research aims to uncover new and better ways to program molecules, as well as limits to molecular programming and energy-efficient computation, through the study of theoretical and empirical models.******A primary goal of my research will be to address a significant barrier currently to design and analysis of molecular programs, namely the lack of good biophysical models. Particularly lacking are kinetics models that can accurately predict the rates at which nucleic strands interact through base pair formation and breakage. There is an opportunity now to make progress, by learning model parameters using valuable data from wet lab experiments of molecular programmers. This work will in part involve the creation of a database of experimental nucleic kinetics data, the first of its kind. In addition, I aim to further improve current thermodynamics models by accounting for important energy features (such as coaxial stacking and asymmetric multi-loop penalties) that are not easily incorporated into traditional dynamic programming secondary structure prediction algorithms. These contributions will support molecular programmers in scaling up current designs from hundreds to thousands of interacting strands, as well as biologists who wish to understand RNA conformational dynamics.******I also want to understand the fundamental capabilities and limitations of molecular programming by studying models at higher levels of abstraction, namely chemical reaction networks (CRNs) and variants. CRNs provide a natural means for specifying and reasoning about highly distributed, asynchronous molecular programs, and a beautiful theory of what can and cannot be programmed with molecules is emerging from study of these models. I plan to contribute to this theory by developing provably fast algorithms for key problems such as leader election, and by developing models analogous to CRNs that can be useful when designing and reasoning about programs that are contained in single strands.**

分子编程是设计携带信息的分子的过程，这些分子以有目的的方式发生反应或执行指令。核酸（DNA 和 RNA 分子）对于编程很有趣，因为它们具有数字序列和动态结构特性，并且因为它们通过与“湿”生物系统自然相互作用来扩展计算设备的范围。分子编程领域的研究人员正在应对令人兴奋的工程挑战，例如利用 DNA 和 RNA 序列构建逻辑电路、纳米级结构，甚至分子行走机器人。在未来几十年中，这些技术可以带来显着的回报，改变我们监测和调节细胞内分子动力学的方式，或者开发可以评估疾病指标浓度并做出相应反应的“智能药物”。**** **我的研究旨在通过理论和经验模型的研究，发现新的、更好的分子编程方法，以及分子编程和节能计算的局限性。******我研究的主要目标是是为了解决目前分子程序设计和分析的一个重大障碍，即缺乏良好的生物物理模型。特别缺乏能够准确预测核酸链通过碱基对形成和断裂相互作用的速率的动力学模型。现在有机会取得进展，通过使用分子程序员湿实验室实验的宝贵数据来学习模型参数。这项工作将部分涉及创建实验核酸动力学数据数据库，这是此类数据库中的第一个。此外，我的目标是通过考虑不易纳入传统动态编程二级结构预测算法的重要能量特征（例如同轴堆叠和不对称多环惩罚）来进一步改进当前的热力学模型。这些贡献将支持分子程序员将当前的设计从数百条相互作用链扩展到数千条，以及支持希望了解 RNA 构象动力学的生物学家。******我还想了解分子编程的基本功能和局限性通过研究更高抽象层次的模型，即化学反应网络（CRN）和变体。 CRN 提供了一种自然的方法来指定和推理高度分布的异步分子程序，并且从这些模型的研究中正在出现关于什么可以用分子编程和什么不能用分子编程的美丽理论。 我计划为这一理论做出贡献，为关键问题（例如领导者选举）开发可证明的快速算法，并开发类似于 CRN 的模型，这些模型在设计和推理单链中包含的程序时非常有用。**