SHF: Small: Programming Networks of Molecular Interactions Using DNA Strand-Displacement Cascades

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AbstractProgrammed molecular self-assembly could be used for the massively parallel construction of nanoscale devices. For example,"Smart drugs" that target drug activity to disease cells and activate in response to specific molecular clues would have minimal side effects and improve therapeutic outcomes. Such tasks require molecular systems that operate autonomously in complex environments, sensing and responding to molecular events. This project proposes an approach for the automated construction of programmable molecular systems using DNA. DNA is not used to store genetic information but as a nanoscale engineering material. Interactions between single-stranded DNA molecules are determined by the linear sequence of these molecules and follow the rules of Watson Crick base pairing. The relatively low cost of synthesis and the predictability of interactions set DNA apart from other (bio) polymers such as proteins, and make DNA an ideal substrate for an engineering approach. In this method, a desired chemical system is first specified using the language of chemical reaction networks. Next, this formal description is compiled into an experimentally testable DNA implementation. Auxiliary multi-stranded DNA complexes mediate the interactions between these signal strands. Because the language of chemical reactions can be used to specify a large number of behaviors -- including chemical oscillations, chaos, digital logic and even algorithmic responses -- this work suggests a powerful approach for generating complex molecular behaviors.The proposed research is tightly integrated with an outreach program with two main aims. The first aim is to develop an educational framework that teaches the interdisciplinary skills required to succeed in molecular programming research. The second aim is to leverage this framework to attract and engage students who are not traditionally involved in electrical engineering or computer science research. A strong educational focus on molecular programming could be an important recruiting tool for attracting more women undergraduates to electrical engineering and computer science. To achieve their aims, the PI and co-PI are engaged in developing and teaching a new interdepartmental curriculum on synthetic biology: The departments of Electrical Engineering, Computer Science & Engineering and BioEngineering are offering a joint sequence of classes on synthetic biology. These courses form an important first step towards developing a broad new educational program on "molecular programming". The PI also participates in the College of Engineering BRIDGE program at the University of Washington, which is designed to increase the participation of underrepresented minorities and women in engineering.