Understanding VRAC-dependent regulation of the NLRP3 inflammasome

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Inflammation is our bodies' response to infection and injury. It is characterised by redness, swelling, and heat and requires recruitment of cells from the blood to an infected or injured area. Typically inflammation is a beneficial response. However, a failure to switch off an inflammatory response, or for it to resolve, can lead to chronic or inappropriate inflammation. This can result in the death of healthy cells and tissue. As we age the bodies control of how it regulates inflammation begins to diminish. Therefore when our bodies are challenged by an injury or an infection they fail to cope efficiently. Much research on mechanisms of inflammation has been carried out with respect to many types of infection and injury in many organs and great progress has been made. However, there are still processes that we just do not understand. The main aim of this proposal is to understand the regulation of the formation of an important inflammatory complex - the NLRP3 inflammasome. We think we have identified new parts of this pathway which we will now test by generating cells and animals in which we have removed specific genes. This will give us information on the specific reactions that occur and their consequence. Through understanding these complex processes we aim to identify new ways of treating disease.