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Circadian clock control of adipocyte metabolism


   Faculty of Biology, Medicine and Health

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

About the Project

Obesity is a major public health issue affecting one third of UK adults, and an estimated 2.1 billion individuals worldwide. The role of circadian clock dysfunction in the development of obesity is becoming clear, with disruptive lifestyles (e.g. shift work) promoting metabolic disorder, obesity, and cardiovascular disease. Metabolic disease (e.g. insulin resistance, dyslipidaemia) is a principal cause of morbidity in obesity, and must therefore be a focus for therapeutic intervention. Recent work has highlighted the importance of adipocyte function in conferring cardiometabolic risk. White adipose tissue (WAT) adipocytes act as an essential energy buffer, safely storing excess energy as triglyceride. However, as obesity develops, adipocytes become dysfunctional, and WAT inflammation and fibrosis develops. We and others have shown that manipulating circadian clock factors alters the adipocyte response to obesity. For example, in mice with adipocyte-targeted deletion of core clock gene Reverbα (Nr1d1), high-fat diet-feeding leads to greater accumulation of fat mass (compared to littermate controls), but with less obesity-associated pathology. This raises important questions: 1) What is the role of adipocyte circadian clock in health? 2) How do clock factors regulate the adipocyte response to obesity? 3) Can the adipocyte circadian clock be exploited for therapeutic benefit?

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.  Candidates with experience in metabolic phenotyping or molecular biology techniques are encouraged to apply. 

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

• Hunter AL, Pelekanou CE, Barron NJ, Northeast RC, Grudzien M, Adamson AD, Downton P, Cornfield T, Cunningham PS, Billaud JN, Hodson L, Loudon AS, Unwin RD, Iqbal M, Ray DW, Bechtold DA. Adipocyte NR1D1 dictates adipose tissue expansion during obesity. Elife. 2021 Aug 5;10:e63324. doi: 10.7554/eLife.63324.
• Hunter AL, Pelekanou CE, Adamson A, Downton P, Barron NJ, Cornfield T, Poolman TM, Humphreys N, Cunningham PS, Hodson L, Loudon ASI, Iqbal M, Bechtold DA, Ray DW. Nuclear receptor REVERBα is a state-dependent regulator of liver energy metabolism. Proc Natl Acad Sci U S A. 2020 Oct 13;117(41):25869-25879. doi: 10.1073/pnas.2005330117.
• Cunningham PS, Ahern SA, Smith LC, da Silva Santos CS, Wager TT, Bechtold DA. Targeting of the circadian clock via CK1δ/ε to improve glucose homeostasis in obesity. Sci Rep. 2016 Jul 21;6:29983. doi: 10.1038/srep29983.
• Hand LE, Usan P, Cooper GJ, Xu LY, Ammori B, Cunningham PS, Aghamohammadzadeh R, Soran H, Greenstein A, Loudon AS, Bechtold DA, Ray DW. Adiponectin induces A20 expression in adipose tissue to confer metabolic benefit. Diabetes. 2015 Jan;64(1):128-36. doi: 10.2337/db13-1835.

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