Sepsis: removing RNA gene protects mice

US researchers have pinpointed a region of the genetic code that can control the immune response to sepsis...
09 February 2021

Interview with 

Susan Carpenter, UC Santa Cruz


A mouse.


When you’re infected with a microorganism, the machinery of the human immune system kicks in and a whole array of specialised chemicals and cells work together to kick out the invader. But sometimes the immune system overreacts and starts to do damage in its own right. This is called sepsis; it’s very hard to treat and can often lead to death. This week US researchers pinpointed a region of the genetic code that can control the immune response to sepsis: specifically, a bit of RNA - the stuff that normally carries the messages from your DNA. Martin Khechara spoke to Susan Carpenter...

Susan - We have identified this genetic material - actually an RNA gene - that when you remove it from an animal, that animal is now resistant; it does not get sepsis.

Martin - How did you find out actually what it does?

Susan - First we started working on this particular gene in human cells, and then we were very excited to see that it is conserved across species. And so we could take a mouse and remove this gene. And what we were really intrigued to find was that that mouse is protected from sepsis.

Martin - What would the molecule do in normal cells? Surely it's necessary?

Susan - We think like everything in the immune system, it's all about balance. This is a gene that's on in cells at high levels normally, and that during an inflammatory response, it goes rapidly down. And so we know that it's playing this role in helping to toggle the responses of that particular cell.

Martin - How can removing just this one thing have such a big effect?

Susan - It really kind of tells us something about the importance of this gene. There's so many genes involved in these responses that just removing this one in particular can have this strong impact. And it's not unusual, we see this with particular protein: if you remove them from the system, they can have positive impacts. So for example, many drugs are designed to target a particular protein during an inflammatory response, and that gives relief to patients.

Martin - If you took me and took this molecule away from my cells, could I still fight disease?

Susan - This story is in its very early phase, but what we can say right now is that with the immune system, everything is about timing. And so we think being able to manipulate the levels of this gene at particular times could have an impact in how you respond to infections.

Martin - When could this discovery one day help people suffering from sepsis?

Susan - Well, that is our ultimate goal with these projects: to get a better understanding, to be able to eventually have some therapeutic targets. And right now, this is in the very early stage. This is very basic research that we've done a lot of work on a mouse model. And our next phase is to move into understanding this better in humans and human cells, from patients with sepsis.


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