June 2011

Rebooting science outreach


Online RNA design game garners unexpected interest from nonscientists. 

It was a typical lab meeting. The latest RNA synthesis results were in, and they were puzzling. The data indicated deviations from the target fold in unexpected ways despite the fact that all eight designs were highly optimized variants of a previously successful design. It looked like another round of synthesis would be inevitable, and the floor was open for suggestions. 

“This is different than the RNAFold prediction, at least using the Turner 1999 parameters.” “Yes, the frequency of the MFE in the ensemble doesn’t track with what’s going on in the leftmost 1x1 loop.” 

“Could there be an error in the SHAPE analysis?” 

“No, position 50 is highly accessible in several similar designs, so it’s not a one-time glitch. But that means we have no idea what position 41 is bonding to …”

The thing was, I wasn’t in lab. I wasn’t even talking to scientists. I was playing an online RNA folding game called EteRNA, and my fellow labmates consisted of computer analysts, project managers, stay-at-home moms (and one dad), retirees and home-schooled teenagers from around the world. And none of them had any formal education in biochemistry. 

EteRNA is a National Science Foundation-funded joint effort between an RNA lab at Stanford University and a computer science lab at Carnegie Mellon University. It’s very slick and well executed; you can dive right into designing RNAs without knowing anything about molecular biology or bioinformatics. It’s all about brightly colored dots, wiggling bonds and getting a higher score than your peers, at least at first. Indeed, 95 percent of the players probably are just substituting EteRNA for their nightly round of Sudoku or Bejeweled.

The other 5 percent

What sets EteRNA apart from other games is the lab portion. Each week, top players create sequences designed to fold into a target shape. They then vote for eight sequences to be synthesized at Stanford and assayed for secondary structure content using the SHAPE primer extension assay (which measures 2'-OH accessibility). Every week, eight lucky players anxiously await the arrival of the experimentally observed secondary structure of their RNA design. When it’s not at all what they expected, they become intrigued, hooked and obsessed. Suddenly, they find themselves spending hours each night in intense online discussions with fellow designers, crunching spreadsheets, looking for patterns and bouncing around ideas for the next round. 

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  • Again, how do you determine the actual RNA structures following their synthesis in the lab? What methods do you use? How do you know that your structure determinations are correct? Have you published any peer-reviewed papers showing the entire EteRNA schema including the preparation of chosen RNA molecules?

    John Vournakis

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