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Uncovering novel genetic pathways that promote ‘healthy ageing’ of vital body tissues: using in vivo animal models and human genetic epidemiology

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  • Full or part time
    Dr H Weavers
    Prof H White-Cooper
    Dr N Timpson
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Our body tissues are frequently exposed to a wide-range of toxic insults that could cause significant damage (1). Toxic molecules are generated within us (as byproducts of metabolism and inflammation) as well as from environmental insults (e.g. radiation, pollution or cigarette smoke). In order to defend themselves, our tissues must switch on powerful protective strategies to help resist and repair the damage (2). Without these pathways, tissues would rapidly age, accumulate cancer-causing mutations and develop disease. Given the same protective mechanisms can be hijacked by cancer cells and drive resistance to anti-cancer treatments (3), our findings will also have important implications for cancer therapy.

Whilst their importance is clear, the exact identity of these protective pathways and how they function are poorly understand. In this interdisciplinary project, we will explore the diverse cellular mechanisms that protect body tissues from stress and investigate their genetic links to human disease (including infertility, chronic wounds and cancer). For this, we will combine state-of-the-art techniques in Drosophila models with cutting-edge human genetic epidemiology. The work has wide-ranging clinical relevance, not only for treating conditions such as infertility and cancer, but clinical activation of these pathways could also help protect patient tissues during surgery.

This inter-disciplinary and cross-institutional PhD project is available on the “MRC GW4 BioMed Doctoral Training Program”. This project offers a unique opportunity for training in a range of state-of-the-art techniques. The student will learn skills in multidisciplinary quantitative methods as well as experimental in vivo biology. The Drosophila studies will include live imaging, genetic manipulation and relevant molecular biology. The Population Health studies will employ cutting-edge genetic epidemiology approaches, including analysis of genetic and epigenetic data. The student will be embedded in the vibrant research environment at the University of Bristol and have the opportunity to interact with our collaborators at the University of Cardiff and internationally (including ETH Zurich). For more information about us, please see our lab website www.tissueresilience.com!

Main supervisor:
Dr Helen Weavers (Biochemistry, University of Bristol); Email: [Email Address Removed]

Secondary supervisors:
Prof Helen White-Cooper (University of Cardiff)
Prof Nic Timpson (Population Health Science Institute, University of Bristol)

International Collaborations:
Prof Sabine Werner (ETH Zurich)

And see this webpage for our research project:
http://www.gw4biomed.ac.uk/files/2018/09/MRC19IIRBr-Weavers.pdf

Funding Notes

Please see this website for “How to apply”: http://www.gw4biomed.ac.uk/available-projects-2/infection-immunity-and-repair-projects/
A full studentship will cover UK/EU tuition fees, a training support fee and a stipend (£14,777 p.a. for 2018/19, updated each year) for 3.5 years. UK and EU applicants who have been residing in the UK since September 2016 will be eligible for a full award; a limited number of studentships will be available to EU applicants not meeting the residency requirement. Applicants who are classed as Overseas for tuition fee purposes are not eligible for funding. More information on eligibility may be found on the DTP's website: http://www.gw4biomed.ac.uk/eligibility/

References

(1) Gracy et al. 1999. Reactive oxygen species: the unavoidable environmental insult? Muat. Res. 428, 17-22
(2) Lee et al. (2005) Nrf2, a multi-organ protector? FASEB J. 19, 1061-6.
(3) Menegon et al. (2016) The dual roles of Nrf2 in cancer. Trends Mol Med. 22, 578-593



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