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

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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.