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Circadian regulation of chronic inflammatory disease


   Faculty of Biology, Medicine and Health

  ,  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

The circadian clock is a biological timer which allows organisms to align their physiology with the 24h environment generated by Earth rotating on its axis. This internal clock regulates many aspects of physiology including sleep-wake cycles, feeding behaviour, hormone secretion, metabolism and immunity. My group is interested in addressing how the circadian clock regulates immunity. Most cells of the immune system possess intrinsic clockwork machinery which allows them to “keep time”. In addition, these cells respond to rhythmic extrinsic signals such as hormones and alter their function in response to daily changes in circulating levels. Work in this group addresses how the clock is involved in the pathogenesis of chronic inflammatory disease. For example, patients with Rheumatoid arthritis often report enhanced joint pain and stiffness in the early morning. This correlates with increased levels of circulating pro-inflammatory cytokines. Using mouse models of chronic inflammatory disease, we assess how sites of inflammation change over the course of a day, and address mechanisms underpinning these changes.

1.     Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area / subject

2.     For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the PhD title.

3.     For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit www.internationalphd.manchester.ac.uk


Funding Notes

Applications are invited from self-funded students. This project has a Band 3 fee. Details of our different fee bands can be found on our website (View Website
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website View Website

References

Hand LE, Gray KJ, Dickson SH, Simpkins DA, Ray DW, Konkel JE, Hepworth MR and Gibbs JE (2020). Regulatory T cells confer a circadian signature to inflammatory arthritis. Nat Commun 11(1): 1658
Poolman TM, Gibbs J, Walker AL, Dickson S, Farrell L, Hensman J, Kendall AC, Maidstone R, Warwood S, Loudon A, Rattray M, Bruce IN, Nicolaou A, Ray DW (2019). Rheumatoid arthritis reprograms circadian output pathways. Arthritis Res and Ther 21:47
Hand LE, Hopwood TW, Dickson SH, Walker AL, Loudon AS, Ray DW, Bechtold DA and Gibbs JE (2016). The circadian clock regulates inflammatory arthritis. FASEB J 30(11): 3759-3770
Gibbs JE, Ince L, Matthews I, Mei J, Bell T, Yang N, Saer B, Begley N, Poolman T, Pariollaud M, DeMayo F, Farrow S, Hussell T, Worthen GS, Ray D and Loudon A. (2014). An epithelial circadian clock controls pulmonary inflammation and glucocorticoid action. Nature Medicine 20(8): 919-926
Gibbs JE, Blaikley J, Beesley S, Matthews L, Simpson KD, Boyce SH, Farrow SN, Else KJ, Singh D, Ray DW and Loudon AS (2012). The nuclear receptor REV-ERBα mediates circadian regulation of innate immunity through selective regulation of inflammatory cytokines. Proc Natl Acad Sci. 109(2): 582-587

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