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Understanding the regulation of sterile inflammation in the brain


Project Description

Sterile inflammatory responses, which occur in the absence of infection, contribute to tissue injury and conditions associated with ageing. The primary inflammatory cytokines associated with sterile inflammatory responses are members of the interleukin-1 (IL-1) family, namely IL-1α and IL-1β. IL-1 release from activated immune cells is regulated by a protein complex called the inflammasome. How IL-1 is regulated in the brain following a sterile insult is completely unknown, but we are now ideally placed to establish the regulation and contribution of inflammasomes and expect to make fundamental advances in understanding brain inflammation. The aim of this project is to fully elucidate the inflammasomes, their location, their regulation and how they contribute to sterile inflammation in the brain.

Funding Notes

This project has a Band 2 fee. Details of our different fee bands can be found on our website. For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website. Informal enquiries may be made directly to the primary supervisor.

References

Lopez-Castejon G, Luheshi NM, Compan V, High S, Whitehead RC, Flitsch SL, Kirov A, Prudovsky I, Swanton E, Brough D, Deubiquitinases regulate the activity of caspase-1 and IL-1β secretion via assembly of the inflammasome Journal of Biological Chemistry, 2013, 288:2721-2733

Savage CD, Lopez-Castejon G, Denes A, Brough D, NLRP3-inflammasome activating DAMPs stimulate an inflammatory response in glia in the absence of priming which contributes to brain inflammation after injury Frontiers in Immunology, 2012, 3:288.

Brough D, Tyrrell PJ, Allan SM, The Regulation of Interleukin-1 in Acute Brain Injury Trends in Pharmacological Sciences, 2011, 32:617-622.

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