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(BBSRC NWD) How do microenvironmental signals affect gastric epithelial integrity and organisation?

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 studentship lays the foundation for a new and exciting interdisciplinary collaboration between biomedical scientists in the Institute of Systems, Molecular and Integrative Biology (ISMIB) and materials scientists and engineers in the School of Engineering (SoE). Innovative approaches will be taken to generate complex in vitro models of gastric tissues that will have far reaching applications across medical research and regenerative medicine.

About this opportunity

The gastric epithelium consists of stem and differentiated cells connected by junctions that preserve polarity, cohesion, and barrier integrity. Its structure is shaped by microenvironmental cues including growth factors and extracellular matrix (ECM). Gastric myofibroblasts act as key stromal regulators, secreting paracrine signals and remodelling the ECM. Epithelial-myofibroblast crosstalk maintains homeostasis and activation in disease can drive epithelial plasticity and malignancy. However, patient-matched myofibroblasts and organoids are rarely integrated to study these interactions.

Matrigel is a widely used ECM that supports organoid culture. However, it is derived from mouse sarcoma and contains undefined components leading to batch-to-batch inconsistency that can affect experimental reproducibility. Its tumour origin and complex composition make it poorly suited for mechanistic studies or clinical translation, as it does not accurately mimic normal human tissue ECM. The student will explore specialised hydrogel matrices designed in the Department of Engineering to better mimic human gastric ECM and improve model fidelity.

This project will uniquely combine gastric PDOs, primary gastric myofibroblasts, engineered ECM environments such as specialised PEG hydrogels, and 3D volume electron microscopy (vEM) to investigate how microenvironmental signals regulate epithelial architecture and function. By resolving cellular differentiation, junctional morphology, polarity, and tissue cohesion across different cellular populations and conditions, this studentship will uncover fundamental principles of gastric epithelial self-organisation and will determine how this is modulated by the stroma in both physiological and disease-mimicking settings.

This approach will generate new understanding epithelial-stromal interactions in human tissue, leveraging cutting-edge tools in imaging, organoid biology, and engineered microenvironments to address key gaps in the literature surrounding ultrastructural mapping of epithelial organisation in human 3D models.

Aims and objectives

The student will investigate how microenvironmental signals regulate the structure and function of the human gastric epithelium. Using PDOs, they will map ultrastructural features across cell populations and examine their remodelling in response to stromal and matrix changes. They will also assess how ECM composition and stiffness affect epithelial polarity, cohesion, and responsiveness to niche-derived cues. Together, these studies will elucidate mechanisms that maintain or disrupt gastric epithelial organisation in different environmental contexts.

Key aims are to:-

  1. Define the cellular composition and ultrastructural organisation of junctional complexes in PDOs across differentiation states
  2. Investigate how stromal-derived biochemical signals alter epithelial structure and function
  3. Examine how ECM composition, structure and stiffness influence gastric epithelial architecture and stromal responsiveness

Further reading

1. Jones LG, Vaida A, Thompson LM, Ikuomola FI, Caamaño JH, Burkitt MD, Miyajima F, Williams JM, Campbell BJ, Pritchard DM, Duckworth CA. NF-κB2 signalling in enteroids modulates enterocyte responses to secreted factors from bone marrow-derived dendritic cells. Cell Death Dis. 2019;10(12):896. https://doi.org/10.1038/s41419-019-2129-5
2. Jardi F, Kelly C, Teague C, Fowler-Williams H, Sevin DC, Rodrigues D, Jo H, Ferreira S, Herpers B, Van Heerden M, de Kok T, Pin C, Lynch A, Duckworth CA, De Jonghe S, Lammens L, Pritchard DM. Mouse organoids as an in vitro tool to study the in vivo intestinal response to cytotoxicants.Arch Toxicol. 2023;97(1):235-254. https://doi.org/10.1007/s00204-022-03374-3.
3. Lloyd KA, Parsons BN, Burkitt MD, Moore AR, Papoutsopoulou S, Boyce M, Duckworth CA, Exarchou K, Howes N, Rainbow L, Fang Y, Oxvig C, Dodd S, Varro A, Hall N, Pritchard DM. Netazepide Inhibits Expression of Pappalysin 2 in Type 1 Gastric Neuroendocrine Tumors. Cell Mol Gastroenterol Hepatol. 2020;10(1):113-132. https://doi.org/10.1016/j.jcmgh.2020.01.010.
4. Sharratt WN, Lopez CG, Sarkis M, Tyagi G, O’Connell R, Rogers SE, Cabral JT. Ionotropic Gelation Fronts in
Sodium Carboxymethyl Cellulose for Hydrogel Particle Formation. Gels 2021, 7(2), 44. https://doi.org/10.3390/gels7020044
5. Lorenzo Lopez, M., Kearns, V.R., Patterson, E.A., Curran, J.M. Passive nanorheological tool to characterise hydrogels. NanoscaleOpen source preview 2025;17(25); 15338–15347

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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

    Supervisory team:

  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

These studentships are 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 does not include any costs associated with relocation. This scheme is open to both UK and international applicants.

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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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