University of Sheffield Featured PhD Programmes
University of Kent Featured PhD Programmes
CoSector, University of London Featured PhD Programmes
Heriot-Watt University Featured PhD Programmes
Loughborough University Featured PhD Programmes

Coping with cellular stress – are we all created equal?


Project Description

Our cells have evolved elegant stress response pathways that protect against the damaging effects of a range of potentially harmful agents. We have recently uncovered differences in the resting and inducible activities of such pathways across species and between humans. This is important because (a) some of these species are used as translational preclinical models, yet may not reflect the behaviour of human stress response pathways, and (b) such differences may underlie the sensitivity of some individuals to pathological insults. To provide a deeper understanding of the extent and consequences of the inter- and intra-species differences in the activities of key stress response pathways, this project will develop new ways of quantifying pathway components in tissues of interest (including our existing biobank of liver tissue from +200 human donors) and use computational modelling to simulate the impact of these differences on the sensitivity of cells to damage.

You will be based in the Institute of Translational Medicine at the University of Liverpool, where you will join a vibrant research group comprising several PhD students and post-doctoral researchers. You will also spend three months of the project working with co-supervisors at Newcastle University and at Certara UK Ltd in Sheffield. Together, the supervisory team will provide you with training in data bioinformatics, quantitative bioanalysis of protein abundance, isolation and culture of primary cells, and computational modelling. This training, delivered in leading academic and industry research environments, will support the scientific progression of the project and enhance your personal development. The fundamental biological understanding gained from this project will improve our knowledge of factors that influence a healthy lifespan and help to explain scenarios in which animal models have failed to predict responses to pathological stress in humans. In turn, this will support a more informed selection of animals for these applications, and provide a critical knowledge base for refining computational models that may ultimately replace the use of animals in some preclinical contexts. The ultimate impact will be a refinement of preclinical research and improvement in human health.

HOW TO APPLY
Applications should be made by emailing with a CV (including contact details of at least two academic (or other relevant) referees), and a covering letter – clearly stating your first choice project, and optionally 2nd and 3rd ranked projects, as well as including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project(s) and at the selected University. Applications not meeting these criteria will be rejected.
In addition to the CV and covering letter, please email a completed copy of the Additional Details Form (Word document) to . A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.
Informal enquiries may be made to

Funding Notes

This is a 4 year BBSRC studentship under the Newcastle-Liverpool-Durham DTP. The successful applicant will receive research costs, tuition fees and stipend (£15,009 for 2019-20). The PhD will start in October 2020. Applicants should have, or be expecting to receive, a 2.1 Hons degree (or equivalent) in a relevant subject. EU candidates must have been resident in the UK for 3 years in order to receive full support. Please note, there are 2 stages to the application process.

References

Characterisation of the NRF2 transcriptional network and its response to chemical insult in primary human hepatocytes – Implications for prediction of drug-induced liver injury, 2019, Arch Toxicol. 93: 385-399.

Real-time in vivo imaging reveals localised Nrf2 stress responses associated with direct and metabolism-dependent drug toxicity, 2017, Sci Rep, 7: 16084.

A RelA(p65) Thr505 phospho-site mutation reveals an important mechanism regulating NF-κB-dependent liver regeneration and cancer, 2016, Oncogene, 35: 4623-4632.

The NF-κB subunit c-Rel regulates Bach2 tumour suppressor expression in B-cell lymphoma, 2016, Oncogene, 35: 3476-3484.

Hypoxia induces rapid changes to histone methylation and reprograms chromatin, 2019, Science, 363: 1222-1226.

Potent and selective chemical probe of hypoxic signalling downstream of HIF-α hydroxylation via VHL inhibition, 2016, Nature Commun, 7: 13312.


Multi-scale, whole-system models of liver metabolic adaptation to fat and sugar in non-alcoholic fatty liver disease, 2018, NPJ Syst Biol Appl, 4: 33.

QSSPN: Dynamic simulation of molecular interaction networks describing gene regulation, signalling and whole-cell metabolism in human cells, 2013, Bioinformatics, 29: 3181-90.

Related Subjects

Email Now

Insert previous message below for editing? 
You haven’t included a message. Providing a specific message means universities will take your enquiry more seriously and helps them provide the information you need.
Why not add a message here
* required field
Send a copy to me for my own records.

Your enquiry has been emailed successfully





FindAPhD. Copyright 2005-2020
All rights reserved.