CDI-Type II: Collaborative Research: Computing with Biomolecules: From Network Motifs to Complex and Adaptive Systems

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Can molecules be organized, or even self-organize, to perform complex tasks? This question seemingly should have an answer in the affirmative, because all the world around us, and especially the living things in it, is a mass of molecules. Yet the complexity of molecular systems, or networks, that chemistry has achieved to date pales in comparison with electronics and computers. A team of chemists, engineers, and computer scientists join forces to explore how molecules can be harnessed to achieve complex behaviors, including simple forms of computation, adaptation, and learning. They will work to discover the engineering principles needed to make large and useful molecular circuits. They will start by building networks of DNA enzymes, where actions of one enzyme stimulate another, just as protein enzymes stimulate one another in a living cell. They will build networks that can detect patterns of change in the environment; for example, the strength and the frequency of a periodic stimulation. Ultimately, they will build large networks that embody the ability to learn (memorize and generalize) patterns of past stimulation, and respond to new conditions in the environment accordingly.Intellectual Merit: The project will develop biocompatible, DNA molecular sensors and actuators that will be of immediate use in pathogen detection, non-invasive diagnostics, and intelligent therapeutics. As the project progresses, these will be combined with ever more capable biomolecular learning machines we will develop, but they can also be used independently by other researchers or medical doctors.Broader Impacts: The project will reach out to underserved communities in Oregon, New Mexico, and inner-city New York, providing high-school students and undergraduates an opportunity to engage in interdisciplinary scientific research.