INSPIRE: Robust Molecular Programming: Advances in the Design and Verification of Reliable Self-Assembling Nanosystems

该INSPIRE奖部分由以下NSF单位资助：计算机与信息科学与工程理事会计算机与通信基础部的软件和硬件基础项目；计算机和信息科学与工程局计算机和通信基础部的生物计算基金；生物学理事会分子和细胞生物科学部的网络和调控计划；计算机和信息科学与工程理事会以及生物学理事会的计算机和通信基金会的生物和计算共享原则基金；以及刺激竞争性研究实验项目办公室（EPSCoR）。分子编程，也被称为DNA纳米技术，利用核酸的信息处理能力来设计纳米级的自组装、可编程结构和设备。过去几年的研究表明，DNA自组装可以实现算法；DNA链位移反应如何实现逻辑电路、神经网络和分子机器人；以及DNA折纸如何创建二维和三维结构，这些结构可以作为靶向药物输送装置或“纳米面包板”，这些装置可以附着在指定的位置。简单地说，分子编程就是在分子尺度上对我们的指令进行编程，它是计算机科学字面意义上的编程。这个项目将结合分子生物学的方法和计算机科学的方法，特别是软件工程的方法，开始发展一门健壮的分子编程学科。这将是一个对DNA纳米系统进行编程的系统过程，尽管环境的化学动力学可能会发生变化，但对DNA纳米系统将会做它们应该做的事情有高度的信心。该项目将开发这种强大的分子编程方法，并与真正的、尖端的DNA纳米技术湿实验室研究相结合。软件工程师为设计和验证可靠的异步系统而开发的方法，以及理论计算机科学家为将随机性与计算相结合而开发的原则，将特别应用于一种全新的方法，以创建更复杂但更健壮的DNA折纸，将这种方法应用于可靠的生物传感器，以及在纳米尺度上模块化计算的新方法。本项目非传统地将软件工程方法直接应用于DNA纳米技术，这对DNA纳米技术及其在医学、信息技术、制造业、能源生产和21世纪社会其他企业的预期应用具有潜在的变革性好处，这些应用更具生产力、可预测性和安全性。该项目还将加强爱荷华州立大学的跨学科STEM教育，并为爱荷华州中部发展生物技术走廊做出贡献。

This INSPIRE award is partially funded by the following NSF units: the Software and Hardware Foundations Program in the Division of Computer and Communications Foundations of the Computer and Information Science and Engineering Directorate; the Bio Computing fund in the Division of Computer and Communications Foundations of the Computer and Information Science and Engineering Directorate; the Networks and Regulation Program in the Division of Molecular and Cellular Biosciences of the Biology Directorate; the fund for Biological and Computing Shared Principles (BCSP) in both the Computer and Communications Foundations of the Computer and Information Science and Engineering Directorate and the Biology Directorate; and the Office of Experimental Program to Stimulate Competitive Research (EPSCoR). Molecular programming, also known as DNA nanotechnology, exploits the information-processing capabilities of nucleic acids to design self-assembling, programmable structures and devices at the nanoscale. Research in the past few years has shown how DNA tile self-assembly can implement algorithms; how DNA strand displacement reactions can implement logic circuits, neural networks, and molecular robots; and how DNA origami can create two- and three-dimensional structures that can serve as targeted drug-delivery devices or "nano-breadboards" to which devices can be attached at specified locations. Simply stated, molecular programming is programming matter to do our bidding at molecular scales, and it is programming in the literal sense of computer science.This project will combine methods from molecular biology with methods from computer science, and especially software engineering, to begin the development of a discipline of robust molecular programming. This will be a systematic process for programming DNA nanosystems with a high level of confidence that they will do what they are supposed to do, despite the probabilistic vicissitudes of the chemical kinetics of their environments. The project will develop this robust approach to molecular programming in concert with real, cutting-edge wet-lab research in DNA nanotechnology. Methods developed by software engineers for designing and verifying reliable, asynchronous systems that scale and principles developed by theoretical computer scientists for integrating randomness with computation will be applied specifically to a fundamentally new approach to creating more complex yet more robust DNA origamis, to applications of this approach to reliable biosensors, and to a new method for modularizing computations at the nanoscale. This project's unconventional application of software engineering methods directly to DNA nanotechnology has potentially transformative benefits for making DNA nanotechnology and its anticipated applications to medicine, information technology, manufacturing, energy production, and other enterprises of twenty-first century society more productive, predictable, and safe. The project will also enhance interdisciplinary STEM education at Iowa State University and contribute to a developing biotech corridor in central Iowa.