About the Researcher: Dr. Rhiju Das (Ph.D., ‘05) is currently an Associate Professor of Biochemistry at Stanford University. At Stanford University School of Medicine, he leads a research lab that combines biochemical and computational perspectives to elucidate the elusive nature of ribonucleic acid (RNA). He is also involved with the creation of EteRNA, an online video game that uses crowdsourcing and collective intelligence to probe players who uncover the mechanisms of RNA folding machinery.
Q: What inspired you to become a researcher? Was there any childhood event that sparked this interest?
Thinking far back, I remember I used to like doing jigsaw puzzles. I knew I wanted to be someone who solved puzzles when I grew up. At first, I thought math might be the best choice, so in high school I planned on being a mathematician. But then I realized that I enjoyed experiments, so I got involved with physics. If you want to solve puzzles every day, then you should become a scientist.
Q: How would you describe your research?
In a computer, I try to simulate the behavior of a molecule called RNA, an ancient oddball cousin of DNA. It plays a key role in every process in life and nearly every disease. Half of my time, I learn about viral RNA diseases. I try to understand how RNA folds up in intricate RNA structures; this is called the RNA folding problem. In the other half of my time, I’m involved with creating new therapeutics with RNA products. This idea of creating new RNA molecules is called RNA design or RNA biomachinery. At its heart, if you want to fold a new molecule, you have to design a new molecule from scratch, so you have to get involved with computational models. It’s mostly computational prediction and design.
Q: How has EteRNA bridged scientific discovery and video games?
It’s an exciting area in our lab. We’re experts in our fields, but for a lot of problems we are trying to solve on RNA folding we haven’t been able to figure out a solution. A few years back, I teamed up with a computer scientist and we created an online-scale video game to solve these problems called EteRNA (pronounced “eterna”). In EteRNA, we provide a hypothetical RNA shape as a puzzle that the players can see and fold. Then, we take the top shapes and in the lab we check to see if it folds up in the way they design.
EteRNA is the first project that has crowdsourced the entire scientific method. We test hypotheses as lab experiments, then go back to the video gamers and ask them to improve their design and solve harder problems. Surprisingly, this player community has repeatedly outperformed scientific experts and the computer.
Q: Interesting! How has EteRNA democratized the scientific method, especially for people who don’t have access to a scientific degree/lab space?
Two or three years ago, we dramatically increased the experimental throughput of EteRNA to increase designs. We challenged players themselves to define puzzles in games. They went bananas and proposed close to 400 micro-projects for other players to solve. We also incentivized them to write hypotheses and conclusions. These 400 micro-projects are scientifically rigorous hypotheses made by players prior to carrying out experiments. They add a new mode of scientific inquiry; we have encouraged players to collate their micro-projects into manuscripts that they are submitting to peer-reviewed publications. The first player-written publication was published last year, and there will be more online.
Q: What are some examples of these micro-projects?
One micro-project focuses on target structures made of RNA. There’s a question of how to create a sequence of RNA to perfectly fold up in a chain in an arranged structure. Symmetry seems intuitively ideal and harmonious in nature. A lot of the players realized something counter-intuitive; they found it was harder to find sequences for symmetric structures. They demonstrated that through a sequence of challenges they gave themselves and to computers. These findings showed that symmetry, although visually appealing to a human, is something you don’t want to have in your design. This arose out of veteran players trying to teach new players concepts and ideas.
Q: You discuss integrating many interdisciplinary perspectives into your research. What sparked this intersection of disciplines?
Being at Stanford! At first, I was working on my Ph.D. in theoretical physics, but then I saw this fascinating talk on a molecular machine called the ribosome. Then I sought out different professors to work with, made a jump from physics to biochemistry, which was so much fun. There’s a nice culture here at Stanford that welcomes students coming from other disciplines from the labs. In my current lab, we draw students from MD/Ph.D. programs, Ph.D. students from chemistry, engineering, physics.
Q: What do you enjoy most about science and research?
I enjoy the confronting of an idea with experiment with the real world. If you talk to EteRNA players, you will see they are different from other video gamers. They won’t tell you about points or rankings, but they tell you about how many designs they have synthesized on the lab. When we have a new project realized on EteRNA, they get really excited about seeing what nature thought about a new molecule. The long-term players share this research. The community is really exciting and hearing people geeking out about biochemistry. It’s not about getting points, but about the key moment where you get your hypothesis tested. A lot of us get a rush from that, and EteRNA is capturing a lot of folks who are scientifically talented but didn’t follow a traditional track.
Q: Lastly, what advice do you have for undergraduates who want to get involved with science?
Try to join a research group as early as possible. When I see really successful folks and postdocs, one common theme is that they got engaged in a research lab early in their careers. It doesn’t matter what field, but it has to be something you really enjoy. For example, my undergrad research was in particle physics. Research exercises the part of your brain that’s different from your classes.