Careers in experimental science allow some researchers to push these frontiers of human knowledge to remote phenomena, from the formation of structure at cosmological scales to the self-assembly of protein enzymes. Non-experts have few channels to deeply experience these revelations due to several barriers: the time required to master technical details, the spatial distance to experts and educators, and the financial expense of careful experimentation. This research is creating a system that removes these barriers to scientific exploration for non-experts, in a frontier field that has attracted wide scientific and public interest: the engineering of nanoscale molecules into complex shapes.
An internet-scale gaming infrastructure is being created that will enable hundreds of thousands of game players to jointly explore the conformational space of ribonucleic acid (RNA) designs. As players explore a simulated RNA design space, their efforts produce a prioritized list of candidate designs which are synthesized immediately in the PI?s biochemistry lab. Experimental results then feed back into the game?s incentive structure. The players? collective efforts thus move beyond simulation into real biochemical experimentation. Also, it is currently unknown how to maximally exploit the ?network effect? of cooperation in multiplayer search games. Successful designs must both reward individual exploration and incentivize knowledge sharing. To unite these goals, the PIs are experimenting with several advances in collaborative scoring. Thus, within the new field of nano-engineering, the system will enhance the toolkit of RNA sequences that self-assemble into complex three-dimensional shapes from the ?bottom-up?: knots, polyhedra, and additional novel shapes never before seen with RNA. The project is producing advances in the nascent field of socially intelligent computing.
Summary: Poorly predictive models of molecular folding fold severely hinder the development of potentially life-saving therapies. Our EAGER award proposed a radical strategy to intensely improving our understanding of bioengineering rules: mass human intuition and collaboration organized through an on-line game. Our game, EteRNA, is the first project to weave wet-lab experimental data within a massively multi-player game. Our approach broad impact, from biochemistry to crowdsourcing. Within biochemistry, we will generate an unprecedented library of hand-crafted, experimentally validated RNAs and formalize high- impact, practical tools for engineering the next generation of RNA therapeutics. Within citizen science, we are pioneering the deep integration of experimental feedback within Internet-scale gaming, a potentially foundational concept within the emerging field of social computation. Outcomes: This National Science Foundation EAGER award funded the initial development of EteRNA. The result has been a great success. After a year of development and beta testing, EteRNA was released on January 11, 2011 (http:// eterna.cmu.edu). Within ten days, by attracting coverage in The New York Times, Wall Street Journal and other media, EteRNA had already enlisted over 20,000 users who had played over 8,000 hours. Among the initial successes, one player solved a test shape, Methanobrevibacter FMBK1, which could not be solved by the widely used InverseRNA algorithm. Another designed a sequence Perception 10 whose in vitro chemical mapping gave close, but not perfect agreement, with the target structure; the player then refined the design to Perception Series 2 whose experimental measurements were indistinguishable from the ideal profile. Over the subsequent year, EteRNA has grown to a thriving community of over 30,000 citizen scientists who now soundly outperform existing RNA design methods. Currently, we are compiling RNA design strategies submitted by the community which we expect to combine into a successful "ensemble strategy" which captures the entire community's intuition. We are preparing these results for high profile publication. None of these successes would have been possible without crucial seed funding through the NSF EAGER program. Further Reading: EteRNA Website - http://eterna.cmu.edu/ New York Times Article - www.nytimes.com/2011/01/11/science/11rna.html 10 Minute Talk on EteRNA - http://youtu.be/A-CCEy3u2WM
