Changing genes to save lives
By Alayna DeMartini
The challenge sounded pretty enticing to a group of undergraduate science buffs: Take a virus that destroys bacteria and change its genes so it stops sepsis, a life-threatening illness.
The students came up with the idea. In this competition, they could have picked any problem that can be resolved by changing the genetic makeup of an organism. They chose to focus on sepsis, when an infection goes on overdrive and can shut down the body’s vital organs.
“It’s a problem that almost every medical person in the field has tried to tackle,” said Satvik Kethireddy, a rising junior in The Ohio State University College of Food, Agricultural, and Environmental Sciences (CFAES).
While treatments for sepsis exist, many have drawbacks. So, a group of 10 undergraduate students from Ohio State, including Kethireddy and two others from CFAES, will work together this summer to create an alternative treatment. They hope to win the International Genetically Engineered Machine (iGEM) competition among students around the world, a contest challenging students to generate any project that changes the genetic makeup of a living organism, usually a bacteria, to solve a problem.
Most cases of sepsis are caused by bacterial infections, which is why the Ohio State iGEM team will start with the natural enemy of bacteria: a virus that destroys bacteria called a bacteriophage or “phage.”
“You can change its DNA relatively easily,” Kethireddy said.
By “relatively easily,” Kethireddy means that he and others on the iGEM team will start with a virus that infects E. coli bacteria and then try to figure out how to change the genes of that virus so it can stop sepsis.
“Where else do you get to use top-of-the-line biological techniques to solve real-world problems and not have the idea and the engineering already all figured out for you?”Satvik Kethireddy
Picture building a house or anything with Lego bricks. One clicks into the next. It’s a lot like that—at least one step in the process. Using pieces that link together, each representing a different gene, the students will tinker to try to find the right combination of genes.
Once they have a lineup they think will work, they’ll test how well the engineered virus reacts to a living organism, likely a blood sample, infected with sepsis.
All of which is exciting for Kethireddy and CFAES teammates Lindsey Shimoda and Yingyi Zhu.
“We’re taking something natural that has evolved over millions of years and tweaking it to make it do something more beneficial that evolution might eventually get to. We’re able to speed up that process,” Shimoda said.
She, along with Kethireddy and Zhu, is majoring in food, agricultural and biological engineering.
Success on this project will require changing only what’s necessary and leaving the rest of the genes intact.
“You don’t want to modify too much of the genome or the bacteria will reject it,” Shimoda said.
Whatever changes they make, they hope will solve a longtime issue for hospitals.
“Sepsis is a very significant problem in medicine, and it’s a very interesting one,” Zhu said. “I think we can make a difference.”
That is especially important for one team member, Lizzie Chung, whose father died in 2018, partly from the long-term effects of sepsis. Complications from multiple sclerosis triggered several bouts of sepsis throughout his life.
“We’re taking something natural that has evolved over millions of years and tweaking it to make it do something more beneficial that evolution might eventually get to. ”Lindsey Shimoda
“Each time, the doctors would tell my family that my dad would likely die because the current treatments for sepsis were not sufficient, and because his body was already so weak,” said Chung, a senior biology major.
“This has motivated me and allows our team to recognize we have the potential to not simply treat statistics, but to treat real people suffering from this.”
Earlier this year, Ohio State’s iGEM team brainstormed with student teams from 18 countries around the world including India, Germany, Brazil, and Belgium.
“We as students have full responsibility for this idea,” Kethireddy said. “Where else do you get to use top-of-the-line biological techniques to solve real-world problems and not have the idea and the engineering already all figured out for you?”
Ohio State’s team received a gold medal last year for creating a database of strategies to keep genetically modified bacteria from surviving outside the lab.
Best case scenario, this year’s Ohio State’s team winds up with an engineered virus, and they test it in sepsis-infected mice, and lo and behold, it stops the disease.
Then their aspirations of a startup won’t seem far off. And why not dream big? But before any startup or plans for medical school or biomedical engineering careers materialize, Kethireddy, Shimoda, and Zhu are looking forward to a warm summer of trial and error in the lab.
(If you’re interested in contributing to Ohio State’s iGEM team, to pay for competition travel expenses as well as summer work in the lab, visit buckeyefunder.osu.edu/iGEM.)