Citizen Science Saturday: Blog 1 – Eterna – the RNA folding game

If like me, you enjoy playing a good video game, then you might already have saved some lives by staying at home and doing just that during the COVID-19 lockdowns. But what if you could more directly contribute just by playing a game?! 

Enter “Eterna” – a citizen science project that uses your solutions to puzzles to improve medicine and contribute to science! (Need to be 13 years or older to play – due to US law) 

Eterna is an RNA folding puzzle game – you may have heard a bit about mRNA – messenger RNA – recently, since this form of RNA is the basis for some of our COVID-19 vaccines. 

RNA is, like DNA, a nucleic acid. One job RNA has is to be a short-lived interpretation of what our DNA says. It can then be read, like instructions, to allow us to make a specific protein- depending on the content of the ‘message’. 

But there are many different types of RNA, and although, unlike DNA it has just one strand, the ‘bases’ or nucleotides that make it up still have pairing rules E.g. G ( for Guanine) and C (for Cytosine) pair together and A (Adenine) pairs with U (Uracil) this time  (there is no T – Thymidine- in RNA) 

Because RNA is one strand it can form interesting shapes by the bases in the strand pairing up together – think your earphone cables in your pocket or a tangled piece of spaghetti! There are certain ways these different bases can bind to each otherkin different combinations and places along the strand that is more favourable and form a more stable RNA molecule.  

Eterna gives you the ability to choose which bases (helpfully colour-coded!) are in which position in your strand and gives you a target shape to achieve in puzzles. E.g. for a hairpin shape you want to make these bases be binding but the ones in the loop not! And there are lots of tricks you will learn to make more stable structures. 

The first thing you can do when you create an account is to go through the tutorial where you learn these valuable tips – e.g. G-C pairs are a thing of beauty – since they provide a very stable pairing!  Along the way you’ll learn bits and pieces about RNA biology! Don’t worry if you get stuck, there are hints available and you can send screenshots to other players for help as well as a useful player-made wiki.  

If you’re the competitive type you can check out your place on the leaderboard! And if you prefer playing together with others there is a chat function as well as the ability to create your own puzzles for other players to solve. There’s a huge community of Eterna players with an active forum , the wiki, and even a discord (that the gamers among you might be familiar with!). There’s even a conference, Eternacon for players and researchers alike! 

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Once you have more experience from the tutorial, and have earned the different bits of ‘lab equipment’ you need, you can have a go at the Lab challenges which are related to real-world goals! In the Lab challenges the best structures will actually get made in real RNA by researchers at Stanford University in the USA who will share their findings to help you make even better RNA structures. 

So what does all this data mean? 

Well, currently Eterna is focussed on 3 main challenges – real world problems that we could solve by understanding RNA folding better: 

  1.  OpenVaccine 

Excitingly, here you could even contribute to COVID research! OpenVaccine aims to find a more stable mRNA vaccine by improving the structure. So far the Eterna community has been able to improve a test mRNA so that it is more stable and ‘read’ better by human cells – and they did better than the usual design tools used in labs! These findings are now being written up to be published in a scientific journal. So it’s a great time to get involved with this challenge! Watch this great video for more info!  

  1. OpenTB 

This challenge aims to come up with a RNA that can be used to detect genes in TB (by this binding activity) to help identify latent  infection (when TB bacteria go undercover and hide out in our lungs!) with TB that will develop into an active infection! As TB is most common in low resource areas the idea is to use the RNA by incorporating it into a paper based test where it will act like a sensor for TB genes! And this stategy could easily be applied to other infectious diseases in the future! 

  1. OpenCRISPR 

You might remember when we talked about CRISPR in our genetics month! This gene editing tool uses RNA to guide the CRISPR to specific DNA sequences. CRISPR gene editing has huge potential as well as being an important tool for biologists to allow changing specific genes 

So CRISPR uses single guide RNAs (sgRNA) that guide the CRISPR Cas9 to specific areas – but some sequences work better than others! Can also use Cas9 to guide a protein to a specific gene e.g. to help it switch on a gene. ETERNA players are working to make an RNA guide that can be turned ‘on’ and ‘off’ – to allow switching genes on and off! 

Over 60,000 players have contributed to publications in this way, and some have even been the lead author leading to 25 journal papers contributing to new scientific knowledge. Players have also contributed to design of many tools to generate stabilised mRNA designs, tools to predict RNA stability and folding! 

So, if that sounds good, head over to https://eternagame.org/ or download the game to your phone to be a scientist on the go from the Google Play Store (Android) or App Store (IOS). Check out the Eterna Youtube account to see some game play and tips in action!  

Take home 

Overview 

  • ETERNA is an online free RNA folding game  
  • Really fun! (the best kind of citizen science!) 
  • Great if you are good at puzzles  
  • The aim is to form the most stable RNA structure  
  • Don’t worry they tell you everything you need to know and you aren’t dropped in at the deep end 
  • Play on PC or on phone (IOS and Android) 
  • Have to be 13+ (due to US law) 

The science results 

  • Has been used to publish multiple papers! 
  • If you’re interested can find out more about the science and techniques behind this 
  • Big projects going on for: 
  • Designing RNA switches for CRISPR 
  • Diagnostic tools to diagnose TB 
  • Generating a more stable COVID RNA vaccine!