EteRNA: Biology plus videogames equals cutting-edge science

Learn how RNA folds, then create your own shapes to test in the lab. Photo: EteRNA
Learn how RNA folds, then create your own shapes to test in the lab. Photo: EteRNA

What class of molecules dominated the primordial stages of evolution, and seems to function as an exquisite operating system for our cells? RNA — the single-stranded cousin of DNA. Scientists suspect that a better understanding of RNAs will allow us to more deeply understand healthy cells, and to design better treatments for those infected by disease. (See below for more RNA info.)

Now EteRNA, a collaborative online game, allows ordinary citizens to help biologists take a crack at solving a challenging RNA mystery, namely: what are the rules governing its folding? Players who assemble the best RNA designs online will see their creations synthesized in a Stanford biochemistry lab!

Drs. Adrien Treuille (Asst. Prof. of Computer Science at CMU) and Rhiju Das (Asst. Prof. of Biochemistry at Stanford) met while completing their postdoctoral research at the University of Washington, and collaborated on another online venture — FoldIt — aimed at understanding protein folding. Hoping that a similar approach could be used to crack the mysteries of RNA folding, they teamed up with doctoral student Jeehyung Lee to create a multi-player RNA-folding game. In an added twist, the RNA that players design is then synthesized in a Stanford biochemistry lab, to see if the folding pattern was indeed correct.

What’s so hard about RNA folding?

“Our computational models are not yet sophisticated enough to correctly predict when a particular RNA design will fold correctly in practice,” Treuille said in an email interview. “It is easy to create RNA designs which computers predict will fold properly, but which will not when synthesized. … We hope that the EteRNA community will be able to put forth a more complete set of hypotheses about when RNAs fold properly, and use these hypotheses to design a set of new RNA designs that fold into exotic, and ultimately medically useful shapes.”

EteRNA is a fun and well-designed game, with an endearing excitement and an award of points when you solve puzzles, allowing you to climb through the rankings as you correctly perform more and more challenges. There are two types of puzzles: Challenge Puzzles and Lab Puzzles. The former are primarily intended to train you, the human, about basic RNA-folding patterns, and are also used to see whether people can solve simple RNA puzzles faster than existing algorithms. The Lab Puzzles ask players to solve real RNA problems, and these potential solutions are then synthesized (“scored”) in the lab.

Complete challenge puzzles in order to be let loose in the EteRNA "lab!"  Photo: EteRNA screenshot.
Complete challenge puzzles in order to be let loose in the EteRNA "lab!" Photo: EteRNA screenshot.

However, what I found particularly enjoyable about playing EteRNA was the sense of community. There’s an ongoing all-player messaging scroll on screen where players can chat or pose questions, and the community votes on the best RNA designs. And through your folding, you have a chance to actually help scientists do their work in a wholly global laboratory.

“The most exciting prospect for me is that thousands of non-expert players might be able to collectively solve fundamental biochemical challenges — with experimental validation! — that are difficult for current algorithms and experts like me. It really will be ‘crowd-sourcing the scientific method.’ That really hasn’t been possible before, has it?” Das said via email.

Want to join? Sign up today and begin folding!
RNA (Ribonucleic acid): Forgotten about RNA? Drag your mind back to high school science class for a moment. Double-stranded DNA is what is wrapped up in our 23 pairs of chromosomes. In order for the DNA codes to be turned into proteins and other building blocks of cells, however, the body uses single-stranded messenger RNA as a kind-of Xerox machine for sections of DNA. Other RNAs are involved in all manner of cellular upkeep, from catalyzing reactions, to communicating responses to cellular signals, to delivering amino acids to ribosomes, and so on.

The building blocks of RNA — adenine, cytosine, guanosine and uracil — attach in 2D sequences that then fold up into 3D shapes. Scientists have some basic understanding of how the RNA tends to fold — that is, they know that uracil tends to stick to adenine, and so forth. However, they do not yet fully understand all of the rules, or why uracil might pair with guanosine under some circumstances. For even more background on RNA and its importance to biology, check out EteRNA’s explanations.

Categories: Biology, Chemistry, Citizen Science, Computers & Technology

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