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(BBSRC NWD CASE) Unravelling the origins, mechanisms and implications of species differences in cellular stress response pathway capacities

Funding
Funded
Study mode
Full-time
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Start date
Subject area
Biological and Biomedical Sciences
How to apply
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Overview

This project tackles a fundamental question in biology: how and why do species differ in their ability to respond to cellular stress? This fully funded PhD project offers the chance to explore this fascinating question at the cutting edge of evolutionary biology, data science and pharmacology/toxicology. The findings will enhance our understanding of mammalian biology, improve the prediction of human drug responses and even inform the development of advanced computational tools, reducing animal use in research while maximising translational accuracy.

About this opportunity

iCASE industrial partner web link: https://www.astrazeneca.co.uk/

Background

Mammalian cells are equipped with intricate biochemical pathways that defend against oxidative stress, protein misfolding and DNA damage. Our recent work has revealed striking differences between some mammalian species in how these cellular stress responses are activated, especially between rodents and humans. For example, rats appear to show a far greater ability to mount protective responses than humans, a difference that may explain why they often fail to predict human drug toxicity. Understanding these differences is vital, not just for improving translational biology research and drug development, but also for enhancing animal welfare and supporting the advancement of novel non-animal testing approaches.

Project Overview

This multidisciplinary project will uncover how and why cellular stress response capacities differ across mammals, combining experimental biology with cutting-edge computational analysis. You’ll explore three key questions:

  1. Evolutionary origins – Have small, fast-living rodents evolved stronger cellular stress responses as an adaptation to their environments?
  2. Genomic mechanisms – Are these enhanced cellular stress responses driven by changes in gene regulation and epigenetic control?
  3. Functional consequences – How do these differences affect how cells respond to drugs, toxins and other forms of stress?

By working with publicly available ‘omics data, and by generating/analysing your own data, you’ll map out evolutionary and mechanistic patterns across tissues from multiple rodent species and humans. You’ll also perform hands-on cell culture experiments to test how these pathways function under stress, and the implications of any species differences that you uncover.

Training and Development

You’ll join a vibrant research group, the Stress Response Lab (www.liverpool.ac.uk/stress-response-lab) led by Professor Ian Copple, based within the Institute of Systems, Molecular & Integrative Biology at the University of Liverpool. You’ll work alongside experienced post-docs and PhD students and receive advanced training in:

  • Comparative biology
  • Multi-omics data analysis
  • Primary cell culture
  • Bioinformatics and digital skills for biological data
  • Experimental design and problem solving
  • Scientific communication and research integrity

A three-month placement at CASE industry partner AstraZeneca’s site in Cambridge will provide you with insight into how academic discoveries drive drug development, and an opportunity to see the real world impact of your research. You’ll emerge from this PhD equipped with a combination of experimental, computational and transferable skills, ready for a rewarding career in academia, biotechnology or the pharmaceutical industry. Come join us!

Further reading

1. Coghlan H … Williams D, Copple IM (2025) Hepatic cellular stress response pathways exhibit species differences in basal and inducible activity, bioRxiv DOI: 10.1101/2025.09.22.677731
2. McDonnell E … Soul J, Rice S (2024) The methylomic landscape of human articular cartilage development contains epigenetic signatures of osteoarthritis risk, Am J Hum Genet, 111: 2756-2772. DOI: 10.1016/j.ajhg.2024.10.017
3. Green JP … Hurst J (2023) Cryptic kin discrimination during communal lactation in mice favours cooperation between relatives, Commun Biol, 6: 734. DOI: 10.1038/s42003-023-05115-3
4. Russomanno G … Copple IM (2023) A systems approach reveals species differences in hepatic stress response capacity, Toxicol Sci, 196: 112-125. DOI: 10.1093/toxsci/kfad085
5. O’Brien K … Williams D … Murray A (2021) Enhanced hepatic respiratory capacity and altered lipid metabolism support metabolic homeostasis during short-term hypoxic stress, BMC Biol, 19: 265. DOI: 10.1186/s12915-021-01192-0

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Who is this for?

Applicants must have obtained or be about to obtain a minimum Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science, engineering or technology.

International applicants

We are only able to offer a limited number of full studentships to applicants outside the UK. Therefore, full studentships will only be awarded to exceptional quality international candidates due to the competitive nature of this scheme.

International applicants must ensure they meet the academic eligibility criteria (including English language) before applying. Visit our English Language requirements page to find out more.

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Liverpool, and is at the heart of all of our activities. The full equality, diversity and inclusion statement can be found on our website.

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How to apply

  1. 1. Contact supervisors

    Supervisors:

    • Prof Ian Copple
    • Prof Jane Hurst
    • Dr Jamie Soul
    • Dr Dominic Williams

  2. 2. Prepare your application documents

    Browse our BBSRC NWD in Bioscience projects and discover one you’re passionate about that matches your interests, ambitions and goals.

    Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.

    How to Apply

    All applications should be submitted through the University of Manchester application portal.

    Apply directly via this link, and select BBSRC DTP PhD as the programme of study. You may apply for up to two projects from the programme via this scheme. To do so, submit a single online application listing both project titles and the names of both main supervisors in the relevant sections.

    Please ensure that your application includes all required supporting documents:

    • Curriculum Vitae (CV)
    • Supporting Statement
    • Academic Certificates and Transcripts

    Incomplete or late applications will not be considered.

    Applications should not be made through the University of Liverpool’s application portal.

    You must submit your application form along with the required supporting documents by the deadline date. You can select up to two projects on one single application, noting the title of each project from the advert and the supervisor name. This can include two projects from one institution or a project from each institution.

    Once you have completed your application, you’ll receive a confirmation email.

    Deadline: Sunday 7th December, midnight (UK time)

    Late or incomplete applications will not be considered.

    If you need help with this stage of the process, or have any queries regarding your eligibility (such as if you achieved unexpectedly low degree results due to extenuating circumstances), please contact the Liverpool BBSRC team for advice at 

  3. 3. Apply

    Finally, register and apply online. You'll receive an email acknowledgment once you've submitted your application. We'll be in touch with further details about what happens next.

    Once you have applied through the University of Manchester portal, and if you are successfully offered a studentship following a formal interview, you will be instructed to apply formally through the University of Liverpool. You must only do this once you have been instructed to do so.

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Funding your PhD

This is a 4 year CASE studentship in partnership with AstraZeneca available to UK and international applicants, and provide funding for tuition fees and stipend at the UKRI rate, subject to eligibility, for four years.. This covers tuition fees and an annual stipend. This does not include any costs associated with relocation.

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Contact us

Have a question about this research opportunity or studying a PhD with us? Please get in touch with us, using the contact details below, and we’ll be happy to assist you.

Liverpool BBSRC team
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