E. coli doesn’t just cause Doom and mayhem in your guts

MIT graduate student creates a novel bacterial screen display to run a video game

10316 doom on bacteria
Ramlan’s drawing depicting the LuxR plasmid repressing the GFP, inhibiting fluorescence
Courtesy of Lauren Ramlan's YouTube channel

In 1993, Doom was released, changing the landscape of first-person shooters for years to come. Doom is a video game where you play as a Martian soldier trying to fight off hordes of invading demons with an arsenal fit for a small army. Despite coming out decades ago, Doom still has a stranglehold on pop culture, and it is considered to be one of the most iconic video games ever created, spoken in the same breath as the Mario series or Pong.

But Doom is not just limited to pop culture — it can also now be found in bacterial culture. Ren Ramlan, a PhD student in Course 20, based her 20.405 Principles of Synthetic Biology class project on proving that Doom can run on E. coli. She was able to have the bacteria arrange itself to show the video game’s title screen, becoming the first to do so. Ramlan was inspired to run Doom on bacteria because of the culture surrounding the game and the running joke of how it can run on anything. From microwaves to pregnancy tests, Ramlan is just continuing the tradition of “Doom running on everything,” an internet phenomenon regarding where people try to have all kinds of electronics process Doom.

“I chose Doom solely because I had seen it as a trend on the internet. I remember reading about somebody running Doom on a toaster,” Ramlan explained in an interview with The Tech. “So, what drove me to pick it because it already had the culture of people doing silly things with it.”

Ramlan stated that running Doom on a microbial display is a unique way of interacting with bacteria. “Bacterial displays, or cellular displays in general, are this really intriguing way for humans to interface with the world of microorganisms.” By having bacteria display a video game, Ramlan reconceptualized how people see bacteria, showing that it can potentially be used outside a lab or medical setting. “I think that perhaps a lot of people don’t really think of bacteria as something that we really look at.”

She was first inspired to do this when MIT Professor Christopher Voigt’s lab created a circuit that they had programmed into E. coli using genetic circuit design, where biological parts interact with each other for a logical function, then choose their display through a fluorescent output state in 2020. 

“It’s really highlighting the computing power of biology,” Ramlan explained. She added that while a bacterial display may not beat a traditional computer screen now, such displays still occupy their own “niche.”

“We think of biological computers as ones that won’t surpass regular computers, but we ourselves are biological computers,” Ramlan stated. “We can highlight how good biology is at computing. I mean, we run on a four-letter code, right?” she said, referencing the four bases found in DNA — A, T, C, and G.

When doing this project, Ramlan chose E. coli because “it’s the model organism when it comes to bacteria.” 

She said, “Most bioengineers, genetic engineers, and synthetic biologists have worked with E. coli at one point or another because it’s just the bacteria everyone uses. As such, it has the most widely characterized genetic toolkit.”

E. coli does not necessarily have an intrinsic property that makes them the go-to for bacterial displays. “You could run this on a lot of different things,” Ramlan explained. “You could use it in human cells, 3T3 [cells]1, HeLa cells2; anything you can give a fluorescent protein to, which is just a piece of DNA that most cells can express, might be able to do this.”

Her experience with E. coli began on Stanford University’s International Genetically Engineered Machine team as an undergraduate, which is an annual synthetic biology competition across universities, so choosing E. coli was an easy solution for her.

“It’s one of those things that I didn’t think about at all because it’s so normal for me to use E. coli,” Ramlan shared. “But then once people started engaging with [my project] on the Internet, I realized that nobody has any idea where that came from.”

As it stands, Ramlan’s Doom simulation takes 70 minutes to generate one frame for the display. It would therefore take 599 years for a player to complete the game based on Ramlan’s calculations. To speed up this centuries-long endeavor, Ramlan joked that “you could theoretically plate a bunch of cells on a bunch of different plates, and then just swap them out each frame so you could [finish the game] quickly.” However, to retain the same cells each time, Ramlan proposed a method called “quenching.”

In her paper, Ramlan writes that quenching speeds up the rate of turning back off once tagged with a fluorescent molecule, increasing the game’s frame rate.

“What makes the cells glow is that they have this fluorescent molecule that’s floating,” Ramlan explained. “You can take a second molecule, and put it on top — it’s like putting a blanket on a lamp.” She added, “That would help because the main issue of what makes the frame rate so slow is that it takes so long for the protein light to fade.”

Ramlan envisions biotechnology to be advanced enough to fully encode Doom on a biological system. Already, Institute research groups seek to achieve similar outcomes, such as Professor Ron Weiss’ lab group, which is interested in coding computational power into neurons. Hopefully, these video games will take less than 600 years to finish.

“In the future, I would do two things,” Ramlan stated. “I would integrate Ron Weiss’ knowledge and approach to biological computing to come up with, theoretically, what would you need to know to fully encode this game just on cells.” 

Ramlan continued, “The second thing is, I would like to try it in the lab!”

1 3T3 cells are fibroblast cell lines derived from mouse embryos.

2 HeLa cells are the most commonly used human cell line, and are noted for their durability.