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Defining the links between ROS and inflammaging in a human model of neutrophil-driven inflammation

Funding
Self-funded
Study mode
Full-time
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Start date
Year round
Subject area
Biological and Biomedical Sciences
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Overview

This self-funded PhD project will increase our understanding of the signalling mechanisms regulating ROS production, and will provide important insight into neutrophil biology in healthy ageing and ways of restoring homeostasis during inflammaging.

About this opportunity

Neutrophils are cells of the immune system that provide protection against infection from micro-organisms (bacteria, fungi). Neutrophils produce large amounts of toxic reactive oxygen species (ROS) which are an important part of the killing repertoire that induce mutations to DNA, lipids and proteins. The production of ROS by the NADPH oxidase (NOX2) enzyme also activates granule enzymes (myeloperoxidase, elastase, gelatinase) which are microbiocidal and help to kill microorganisms. Intracellular signalling also induced by ROS is essential for the release of neutrophil extracellular traps (NETs). NETs are beneficial during infection but in the case of sterile inflammation, eg inflammation associated with ageing, “inflammageing”) NETs and ROS promote inflammation and damage host tissues. Mitochondrial ROS production (mtROS) also promotes NET release in the absence of NOX2-derived ROS.

Plasma membrane receptors that activate ROS production are well characterised on neutrophils. However the down-stream effects of intracellular ROS production are less well understood and there is evidence that ROS may be either pro-inflammatory (activating production of inflammatory molecules and NETs) or anti-inflammatory (inducing a stress response that induces cell death). Neutrophil ROS production clearly represents an important physiological mechanism in regulating the resolution of inflammation after infection and the dysregulation of inflammation during inflammaging.

Plan of work

Models
  1. Liverpool. Human neutrophils activated with cytokines or toll-like receptor agonists to induce inflammageing
  2. Newcastle. CRISPR mutant and wild-type C. elegans.
Objectives
  • Objective 1: Identify the changes to the neutrophil proteome and phospho-proteome that are induced in response to ROS (neutrophil redox proteome) over 20 min using data-independent acquisition mass spectrometry (DIA MS). (Liverpool)
  • Objective 2: Use CRISPR mutant C. elegans to determine the effect of key phosphorylation events (identified Obj1) on the innate immune response to C. albicans and S. aureus. (Newcastle)
  • Objective 3: Inhibit ROS and mtROS chemically to determine the effect of ROS production on pro-inflammatory neutrophil functions (NET release, cell death, production of inflammatory molecules, gene expression) and bacterial killing. (Liverpool)

The project will increase our understanding of the signalling mechanisms regulating ROS production will provide important insight into neutrophil biology in healthy ageing and ways of restoring homeostasis during inflammaging. It will also provide training in human and non-human models of the immune system and transferrable skills in phospho-proteomics, statistical analysis, bioinformatics and CRISPR.

Who is this opportunity for?

This project is open to self-funded UK and international applicants.

Further reading

  • Abdullah G et al. New insights into healthy ageing, inflammation and frailty using metabolomics, Frontiers in Aging 2024 5
  • Wright H L et al. Rheumatoid arthritis synovial fluid neutrophils drive inflammation through production of chemokines, reactive oxygen species and neutrophil extracellular traps, Frontiers in Immunology 2021
  • Kalyuzhnyy et al. Profiling the Human Phosphoproteome to Estimate the True Extent of Protein Phosphorylation. J Proteome Research 2022, 21, 6, 1510–1524
  • Byrne et al. Aurora A regulation by reversible cysteine oxidation reveals evolutionarily conserved redox control of Ser/Thr protein kinase activity. Sci Signal. 2020 13(639) doi: 10.1126/scisignal.aax2713.
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How to apply

  1. 1. Contact supervisors

    To apply to this project, email your CV and cover letter to the primary supervisor, Dr Helen Wright, before submitting a formal online application:

  2. 2. Prepare your application documents

    You may need the following documents to complete your online application:

    • A research proposal (this should cover the research you’d like to undertake)
    • University transcripts and degree certificates to date
    • Passport details (international applicants only)
    • English language certificates (international applicants only)
    • A personal statement
    • A curriculum vitae (CV)
    • Contact details for two proposed supervisors
    • Names and contact details of two referees.
  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.

    The application deadline for this project is 8 April 2026.

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Fees and funding

Your tuition fees, funding your studies, and other costs to consider.

Tuition fees

UK fees (applies to Channel Islands, Isle of Man and Republic of Ireland)

Full-time place, per year - £5,006

International fees

Full-time place, per year - £31,250

Fees stated are for the 2025-26 academic year.


Additional costs

We understand that budgeting for your time at university is important, and we want to make sure you understand any costs that are not covered by your tuition fee. This could include buying a laptop, books, or stationery.

Find out more about the additional study costs that may apply to this project.


Funding your PhD

This opportunity is for students with their own funding. Funding should cover tuition fees, living expenses and research expenses (bench fees). The research group cannot provide supplementary funding or provide advice about how to apply for funding. 

If you're a UK national, or have settled status in the UK, you may be eligible to apply for a Postgraduate Doctoral Loan worth up to £30,301 to help with course fees and living costs.

There’s also a variety of alternative sources of funding. These include funded research opportunities and financial support from UK research councils, charities and trusts. Your supervisor may be able to help you secure funding.


My qualifications are from United Kingdom.

Scholarships and bursaries

We offer a range of scholarships and bursaries that could help pay your tuition fees and living expenses.

Duncan Norman Research Scholarship

If you’re awarded this prestigious scholarship, you’ll receive significant funding to support your postgraduate research. This includes full payment of your PhD fees and a cash bursary of £17,000 per year while you study. One award is available in each academic year.

John Lennon Memorial Scholarship

If you’re a UK student, either born in or with strong family connections to Merseyside, you could be eligible to apply for financial support worth up to £12,000 per year for up to three years of full-time postgraduate research (or up to five years part-time pro-rata).

Sport Liverpool Performance Programme

Apply to receive tailored training support to enhance your sporting performance. Our athlete support package includes a range of benefits, from bespoke strength and conditioning training to physiotherapy sessions and one-to-one nutritional advice.

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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.

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