A cure to a disease is usually discovered in a scientific lab after extensive research that spans many months or years. The John P. Atkinson lab in the Division of Rheumatology at Washington University School of Medicine in St. Louis has a team of dedicated scientists making discoveries about our immune system. Kathryn Tristan, assistant professor of medicine and research scientist, has been involved in this type of work for more than 40 years.
“I study the immune system, how it regulates itself. In particular, a facet of the immune system called the complement system,” said Tristan.
The complement system is the part of the immune system that improves the ability of antibodies and cells to clear microbes and damaged cells from our bodies. The complement system creates defense proteins that run through the blood stream on the lookout for bacteria or viruses that try to infect us.
Inside the Atkinson lab, Tristan is among the scientists looking at how the complement system regulates itself. They also study RVCL, a rare genetic disease, and a number of other conditions and hypothesis.
While collaborating with scientist Dr. Claudia Kemper from the National Institutes Of Health, a major discovery was made. The National Institutes of Health (NIH) is one of the world’s foremost medical research centers, an agency of the U.S. Department of Health.
“She (Kemper) was publishing a paper on the use of T-Cells. T-Cells float around the blood. They are an immune system cell,” Tristan explained. “She happened to find out that it has this component, C3. So she published her paper on that and left it that way, but we wanted to explore more. ‘What do you mean this cell has C3? This new protein inside of it. And how much of it? How does that work?’”
C3 is normally made by the liver to patrol the bloodstream to help the body fight off illness but they found that each individual cell had its very own store of C3 that it uses for its survival. Scientists refer to C3 as a hidden immune arsenal that each cell has at its disposal to help it survive.
Until Kemper’s discovery, no one knew about it. Tristan explained the significance of each cell having its own immune system that is completely independent from what floats around the human body for defense. C3 can be used to create an immune system inside the cell, a different intracellular system.
“No one would have guessed an immune system protein could be broken down to be used as fuel for the cell,” said Tristan. “So that was quite surprising but also quite fascinating.”
For the next three years, Tristan along with Kemper and other scientists from around the world studied C3 within cells. Then they published their findings in a prestigious immunity journal.
“We got quite a stir of people saying, ‘Wow we didn’t know that inside the cell could also have a system of defense such as this’,” Tristan said.
The new findings could help scientists develop a medicine that could potentially increase C3 levels if a cell is deficient, as well as lower C3 levels if the levels are too high. Tristan explained more research is needed.
“You could take a look at cancer and say cancer tends to make more of different proteins to protect itself. Are the cancer cells making more of the C3 in order to fight off natural defenses? These are questions that we need to find out because it’s so early in this discovery. Çould it have an effect on understanding and defeating cancer ultimately?”
Applying this new information about an intracellular immune system is the next step. Tristan said it’s up to scientists around the world to take this discovery and figure out how to apply it to their research.
“But like all discoveries, what is going to be the impact? What is going to be the ultimate use in therapeutics? Those are the fun things that we are finding out,” she said. “Why does the cell have this?”
It’s a discovery for the record books and an entry on Tristan’s best career moments’ list.
“Scientists are always looking for that ‘Eureka moment’. And there are so few because it’s such a labor. You do an experiment, you repeat an experiment, it doesn’t quite work out, you try this, try that. When I actually found this inside the cell, I wrote in my lab book, “Eureka!” So it was my first real ‘Eureka moment’. We’ve had things that we’ve discovered over time, but something that no one really discovered before? It’s like going where no one has gone before.”