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: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=708226
• 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反应或执行指令。核酸——DNA和RNA分子——编程很有趣，因为它们的数字序列和动态结构特性，还因为它们通过与“湿”生物系统自然地相互作用，扩展了计算设备的范围。分子编程领域的研究人员正在解决令人兴奋的工程挑战，如从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。在未来的几十年里，这些技术可以带来巨大的回报，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”。