HCC: Large: Collaborative Research: DNA Machine Builder: Creative molecular-machine design through mass-scale crowdsourcing

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This project will develop and evaluate methods by which large numbers of humans, together with computers, can advance the field of synthetic biology by assembling a corpus of creative designs of molecular machines built from DNA segments as well as other molecular structures. Specifically, it will develop a massively-distributed DNA machine construction game that will enable human worldwide collective creativity to be applied to problems ranging from the design of novel self-organizing materials to smart therapeutics that can sense and respond to their environment. The innovative approach is to cast problems of constructing molecular nano-machines with specific functions as a collaborative machine design game governed by the rules of DNA strand interactions. This approach points to a new paradigm for future science, in which a large group of people together with computers work on difficult creative problems, finding solutions that could not be found by computers alone, or by people alone, or without the massive participation of users. If successful, this approach could change science profoundly, with wide-ranging impact on many disciplines including nanotechnology, biochemistry, medicine, and even social and economic behavior analysis. Although the project specifically focuses on games that use DNA strands as principal building blocks of nano-machines, the potential set of applications is large, and encompasses three of the most significant problems facing humanity today. The primary goal of the computer game is to develop and focus collective creativity towards a design space of machines governed by DNA molecular mechanisms. It is currently not known whether this form of sophisticated scientific design creativity can be developed rapidly with non-experts. It is also unknown whether this developed creativity can exceed the current capabilities of the scientific community. This project aims to answer a number of fundamental questions: How does one develop computer games to maximize targeted human design creativity? What are the guiding principles of successful molecular design games? How do we generalize game-development principles to the widest possible range of synthetic biology problems? How can we develop a collective creative design process that outperforms any individual creativity? How do we learn from the way people play the game, and distill their strategies towards stronger automated approaches? The successful outcomes of this project can have a wide ranging impact on health and medicine. One such problem is the design of diagnostic devices and imaging technologies. The game players will work to develop DNA sensors and circuits that can autonomously analyze and interpret the information encoded in a set of molecular disease markers. This approach will enable new devices for multi-analyte testing in low resource settings and will lead to novel medical imaging technologies. Another challenge is design of novel targeted therapeutics, in this case novel RNA-based therapeutics that can autonomously sense and analyze their environment and activate a therapeutic response only where required. A third problem is design of novel materials. This project will develop DNA nanostructures with the potential for the massively parallel self-assembly materials with desired electronic, optical, or chemical properties. These materials will find applications in areas from artificial photosynthesis to biofuels production. This effort will have positive broader impacts for informal science education. The game will reach out to people of all demographic profiles in hope of educating everyone about key molecular research challenges, empowering them to solve important scientific problems, and engaging them in research and science in general. Hopefully, the best scores in these games turn into seminal discoveries with deep impact on people's lives. Also, undergraduates will be involved directly in game development, and a course centered around prototyping of molecular games will be offered. Furthermore, the research team will work with education scientists to develop a new curriculum about DNA and how nature uses molecular mechanisms to achieve function. The curriculum will be anchored around the DNA Machine game and will be piloted in US high schools.