How cells communicate with each other is crucial in our understanding of the inflammatory response and could uncover new targets for biological drugs.
What is this research looking at?
The cells in our body talk to each other by producing and releasing proteins. These proteins act as messengers, giving cells instructions on what they should do next.
IL-1β is one of these messenger proteins. In the right amount, it supports helpful inflammation, for example, telling cells to remove harmful bacteria during an infection. But, if IL-1β is not regulated properly and there is too much around, it can be harmful and lead to chronic inflammation, as in Crohn’s Disease and Ulcerative Colitis.
Another messenger protein called optineurin (OPTN) can tell cells to stop releasing IL-1β. Researchers know that people with Crohn’s Disease have less OPTN than healthy people, so they do not have enough of the messages that could stop the inflammation in their gut.
We don’t know exactly how OPTN stops cells releasing IL-1β, so the first part of this research project will look at what is happening inside cells when OPTN delivers the ‘stop’ message.
The second aim of this research project is to create organoids. Organoids are made using cells taken from the human body – in this study the researchers will be using cells taken from gut biopsies and blood samples from people with Crohn’s or Colitis. These groups of cells are grown together in the lab to create a 3D model of the gut. Organoids better mimic what is happening in the human body where cells are interacting and talking to each other all the time.
The researchers will use these organoids to understand how gut and immune cells talk to each other under different conditions, for example, when certain genes are turned on or off, or when cells are faced with bacteria during an infection.
What do researchers think this could mean for people with Crohn's or Colitis?
How cells talk to each other is a crucial step in the inflammatory process. This study will give researchers a new insight into how inflammation is being controlled in Crohn’s and Colitis. Knowing how messenger proteins instruct cells to either increase or decrease inflammation could provide new targets for biological drug treatments. The creation of organoids with cells from people with Crohn’s or Colitis have huge potential to further our understanding in this area and will be a useful and relevant model for testing potential new treatments.
Who is leading this research: Professor Andrew Smith, Microbial Diseases, Eastman Dental Institute, University College London
Our funding: £179.755
Duration: 36 months (24 months funded by us)
Official title of application: Investigation into the role of optineurin and autophagy in IL-1B secretion and gastrointestinal inflammation