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School of Medicine
Whether large or microscopic, any organism must have a way to deal with stress, says biochemist Jungsan Sohn of Biophysics and Biophysical Chemistry.
You’re now studying an immune system component called the inflammasome. Did you start out in your scientific career intending to focus on this molecule?
SOHN: No. When I was in graduate school, like most students, I experienced a certain degree of stress. So one day I found myself thinking, How can a cell sense stress? What mechanisms are involved?
Eventually, when I did my postdoc, I decided to study how a one-celled organism, the bacterium E. coli, responds to stress.
How do you stress bacteria?
SOHN: We used heat. It turns out that E. coli contains a special stress-sensing protein in its membrane. When the bacteria are exposed to heat, the protein activates the stress sensor. That sets off a cascade of biochemical events that end up releasing enzymes to fix any damage heat has caused the cell.
But now you no longer study bacteria. You study human and mouse proteins. Why did you make the switch?
SOHN: As a postdoc, I started to read about other stress systems. The most compelling were inflammasomes, protein complexes that help the innate immune system respond to bacteria and other pathogens—essentially molecules that help higher-level organisms respond to stress. I realized it could be my next project.
So both the inflammasome and bacterial stress sensors perform similar jobs. Would it be accurate to say that the inflammasome evolved from the bacterial stress sensor?
SOHN: Not exactly. They are very distant from each other. However, what’s interesting is that these unrelated systems use the same biochemical principles to pass along the message that a type of stress threatens the cell. Both use something called proteolysis, which involves an enzyme cleaving a protein. Proteolysis is an incredibly effective mechanism, as it provides both speed and control: The cell can quickly respond to the threat but the cell also has tight control over the enzyme’s activity.
What else has inflammasomes? What is the most primitive organism found to have an inflammasome?
SOHN: It can be found in all high eukaryotes, from sea urchins to humans. Plants have them. The most primitive organism to have one is the tree.
Insects don’t have them. Pathogenic eukaryotes such as parasites and fungus do not have inflammasomes.
But even if they don’t have inflammasomes, all animals, plants and insects have an innate immune system—mechanisms to sense and destroy disease-causing invaders. It is the most ancient and well-conserved form of defense mechanism found in living organisms. Everything needs a way to protect itself.