Revisiting 'classic' SHAPE switch labs as we get ready for future switches

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The Eterna developer team is in the middle of some exciting switch developments -- we're putting together a paper on the Array switches (like the FMN/MS2 puzzles) and piloting a new experimental process that would let us get data back on switches on the timescale of a week or two. 

We're also revisiting some of the work we did in 2012-2014 that really kicked off Eterna's riboswitch explorations.

That was the time period when we used chemical mapping ('SHAPE') to test if we could design RNAs to switch between two target structures when they bound to the FMN molecule.

At that time, we weren't sure if player designs that looked good by SHAPE really did go between the two target structures, which is partly why we developed new experimental methods (like the high-throughput RNA arrays and MS2 binding). But now the Das lab has developed some methods to more directly test if base pairs are present in an RNA, in either -FMN or +FMN conditions. Its called lock-mutate-map-rescue, and here's a recent paper:

https://elifesciences.org/content/7/e29602

The method is, however, expensive and time-consuming. We'd like to no go back to some classic SHAPE switches and pick a few candidates (3 to 6) for testing in late 2018. Can you help us nominate a few? jandersonlee and EliFisker, who were around in 2012-2013 have already made some nominations:

https://docs.google.com/spreadsheets/d/1tVmYzNk0FWP65DzjaOw458wtRNnpXc7gGB_xSEocOX8/edit

We'd love to have veteran players from that period as well as newer folks who have a 'fresh eye' help us discuss these designs. As a reminder, the lab names from that period were:

R52    Simple RNA Switch
R53    Simple RNA Switch
R54    Simple RNA Switch
R55    Simple RNA Switch
R56    Simple RNA Switch
R57    Simple RNA Switch, "The Thinker" for new players
R58    Simple RNA Switch, "The Thinker" for new players
R59    FMN Aptamer 2.0
R60    FMN Aptamer 2.0
R61    FMN_Switch2.0
R62    FMN_Switch2.0
R63    FMN_Switch2.0
R64    FMN_Switch2.0
R65    FMN_Switch2.0
R66    Hand_and_finger,sea_turtle
R67    hand_and_finger,sea_turtle

and

"LabPuz02 by JR"
"Bistable 3 by jnicol"
"Hair Trigger by space_miser"
"Will It Bind? by jmf028"
"Stratospheric by Dennis9600"
"Phase II - 1 by ElNando888"
"LS2 by c-quence"
"Anchor 2.0 by ribonucleic"
"Day 2 by wateronthemoon"
"Alive and kicking by Eli Fisker"
"Laydown and Jump by rnjensen45"
"McSwitch by Meechl"
"Water Snake Redux by jruaya"
"My Screw-Up Corrected? by SpaceFolder"
"Nincompoop by hoglahoo"
"Lines by starryjess"
"Bound state has a zigzag by stevetclark"
"Chirality by kcabral28"
"Switch Test 1 by Brourd"
"Top Notch by jmf028"
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rhiju, Researcher

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Posted 1 year ago

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