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Role of cutaneous circadian clocks in gating skin repair


Project Description

Biological clocks play a key role by temporally controlling the function of whole organisms (including humans) and individual tissues and cells to be aligned with the rhythmic environment. These cell-autonomous circadian clocks are responsible for generating 24 hour rhythms which control when cells divide, how cells and tissues respond to damage and if and when the damage can be repaired within the daily cycles of light/darkness and rest/activity. Disruptions to these clock rhythms (e.g. during ageing) have been linked to increased risks of various human diseases. Whilst it is clear that skin also possesses these peripheral clocks, little is known regarding the role which they play in determining how susceptible human tissues are to damage (by ultraviolet radiation for example) or repair (by day or night creams). This PhD project aims to characterise the influence of skin clocks on: i) the physiology of human skin and skin cells, ii) the susceptibility to ultraviolet radiation and iii) the success of topical anti-ageing treatments to promote repair. The ultimate goal is to optimise repair of damaged skin using chronotherapy (timing the delivery of medication) or other body clock-based approaches. Importantly, as skin contains many similar proteins to internal organs (such as for arteries and lungs) yet is more accessible, this research will provide an ideal experimental system in which to test the role of clocks on human biology. The student will become well versed in cutting-edge circadian clock biology and skin biology, the physics and biology of UVR and the ethical and practical aspects of recruiting human volunteers in a clinical setting. We expect to place the student with Walgreens Boots Alliance, hence a great opportunity for the student to be exposed to the commercial realities of product development and marketing within a large, multi-national commercial environment.

Applicants are expected to hold, or about to obtain, a minimum upper second class undergraduate degree (or equivalent) in cell biology, physiology or biochemistry. A Master’s degree in a relevant subject and/or experience in skin biology/ageing is desirable. 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.”

Funding Notes

Fully funded University of Manchester award with Walgreen Boots. Studentship funding is for a duration of four years to commence in September 2019 and covers UK/EU tuition fees and an annual minimum stipend (£15,009 per annum 2019/20). On the online application form select PhD Dermatological Sciences.
For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

Yang, N., Williams, J., Pekovic-Vaughan, V., Wang, P., Olabi, S., McConnell, J., Gossan, N., Hughes, A., Cheung, J., Streuli, C. H. & Meng, Q-J (2017). Cellular mechano-environment regulates the mammary circadian clock. Nature communications. 8, p. 14287

Dudek, M., Yang, N., Ruckshanthi, J. P. D., Williams, J., Borysiewicz, E., Wang, P., Adamson, A., Li, J., Bateman, J. F., White, M., Boot-Handford, R., Hoyland, J. & Meng, Q-J (2017). The intervertebral disc contains intrinsic circadian clocks that are regulated by age and cytokines and linked to degeneration. Annals of the Rheumatic Diseases. 76, 3, p. 576-584

Dudek, M., Gossan, N., Yang, N., Im, H.J., Ruckshanthi, J.P.D., Yoshitane, H., Li, X., Jin, D., Wang, P., Boudiffa, M., Bellantuono, I., Fukada, Y., Boot-Handford, R.P and Meng Q-J (2016). The chondrocyte clock gene Bmal1 controls cartilage homeostasis and integrity. J Clin Invest. 126, 365-376.

Hibbert SA, Watson RE, Gibbs NK, Costello P, Baldock C, Weiss AS, Griffiths CE, Sherratt MJ (2015). A potential role for endogenous proteins as sacrificial sunscreens and antioxidants in human tissues. Redox Biol. 5, 101-113.

Naylor EC, Watson RE, Sherratt MJ (2011). Molecular aspects of skin ageing. Maturitas. 69:249-256.

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