Completed Infection & Immunity Lungs & Breathing

Elucidation of mechanisms that restrict the activation of Toll-Like Receptors and the IL-1 receptor to prevent inflammatory and autoimmune diseases

Funder MRC (part of UKRI)
Recipient organisation University of Dundee
Funding £1.6M
Period Mar 2018 — Mar 2023

In plain English

AI plain-English summary

The immune system’s off switch keeps jamming, and this project aims to figure out why—and how to fix it. When the body fights an infection, immune cells release powerful signals that can also damage healthy tissue. Normally, built-in brakes stop this response once the threat is gone. But in millions of people with arthritis, asthma, colitis, lupus, or sepsis, those brakes fail. The immune system stays stuck in attack mode, causing chronic inflammation and autoimmune damage. Researchers already know some of the proteins that act as these brakes, but the precise mechanisms that keep them working—or let them fail—remain unclear. This project will map the molecular controls that prevent Toll-Like Receptors and the IL-1 receptor from over-activating. The work is fundamental science: it seeks a deeper understanding of how the immune system regulates itself, not an immediate treatment. However, the team is already collaborating with pharmaceutical companies to target the controller proteins they have identified. If successful, this could lead to new drugs that restore the immune system’s natural off switch, offering a more precise way to treat inflammatory diseases—and potentially helping the immune system attack tumour cells in some cancers.

View original technical description
The immune system is vital for defense against microbial pathogens, such as bacteria and viruses, but if it is activated too strongly or cannot be switched off efficiently, it can cause serious tissue damage and lead to many inflammatory and autoimmune diseases. These diseases include arthritis, asthma, colitis, fibrosis, lupus, psoriasis and sepsis, which affect the lives of millions of people. It is therefore critical to not only understand the mechanisms that switch on the immune system, but also those that prevent it from being activated to strongly and those that switch it off again when it is no longer needed. Our research proposal builds on novel and exciting recent findings made by our research teams, which have advanced the understanding of how the immune system is kept under control and switched off. In the longer term, our research may lead to the development of improved drugs to treat inflammatory and autoimmune diseases. It may also help to treat some forms of cancer because the immune system has a key role in helping to destroy the tumour cells that cause cancer. With these aims in mind, we are working will both University researchers and pharmaceutical companies to launch and accelerate the development of new medicines to treat these diseases that target key controller proteins that our research has identified.

View the original record at the funder ↗

Researchers

Philip Cohen (Principal Investigator)Simon Arthur (Co-Investigator)

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Original classification

Research Grant

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