Overview
We are looking for a motivated, curious, and ambitious student to join a dynamic research team focused on transforming how we understand and treat gastric cancer. You’ll work within a supportive, interdisciplinary team of scientists and clinicians who are all driven by a shared mission to improve cancer outcomes and who value creativity, resilience, and fresh thinking.
About this opportunity
Gastric cancer remains one of the leading causes of cancer-related mortality worldwide, often diagnosed at an advanced stage with limited treatment options. Patient-derived organoids, routinely generated in the primary supervisor’s laboratory, have shown promise as preclinical models that preserve tumour architecture and genetic diversity. However, they lack a native tumour microenvironment, limiting their ability to predict in vivo drug responses. There is a critical need for integrated models that retain tumour fidelity while incorporating stromal components to better predict patient responses and enable new therapeutic strategies.
Objectives:
This DiMeN studentship will develop and validate a novel in ovo organoid xenograft model of human gastric cancer using the chick chorioallantoic membrane (CAM) assay. Incorporating the tumour microenvironment, this model will serve as a scalable, physiologically relevant platform for drug testing and biomarker discovery.
The student will:
- Establish and validate an in ovo organoid xenograft model of human gastric cancer
- Recapitulate the human gastric tumour microenvironment within the CAM model
- Evaluate therapeutic responses to standard and novel drugs and identify translational biomarkers
Novelty:
This platform integrates human patient-derived gastric organoids with a live, vascularised environment that supports angiogenesis, stromal interactions, and immune cell infiltration. Unlike conventional in vitro, organoid or reconstituted organoid models, it enables investigation of tumour-microenvironment crosstalk, which is critical for understanding treatment response and tumour progression. The inclusion of patient-derived myofibroblasts allows exploration of human stromal contributions to drug resistance and tumour dynamics.
Timeliness:
With increasing emphasis on personalised oncology and mechanism-based therapies, physiologically relevant models that reflect both tumour-intrinsic and microenvironmental features are urgently needed. Advances in organoid and multi-omics technologies make this an ideal time to develop such integrated systems. This project is well-positioned to accelerate biomarker discovery and therapeutic validation.
Experimental Approach:
The student will generate patient-derived gastric cancer organoids with support and expertise from a recently established North West Cancer Research gastric cancer patient-derived organoid hub led by the primary supervisor. They will integrate organoids into an in ovo model with support from the University of Liverpool Egg Facility.Standard-of-care chemotherapy and novel compounds (eg from Galytx Ltd) will be evaluated in the model via imaging, viability assays, histology and molecular profiling (RNA-seq, proteomics) of tumour tissues and serum. Co-engraftment of myofibroblasts will enable analysis of tumour–microenvironment interactions. Results will be compared to standard organoid models and matched patient treatment responses. Training will be provided and encouraged in all aspects of the study. Informal enquiries are welcomed.
Benefits of being in the DiMeN DTP:
This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle, York and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of-the-art facilities to deliver high impact research.
We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.
Being funded by the MRC means you can access additional funding for research placements, training opportunities or internships in science policy, science communication and beyond.
Further information on the programme and instructions on how to apply, including a link to the application portal, can be found on our website https://www.dimen.org.uk/
Further reading
1. Johnston LJ, Barningham L, Campbell EL, Cerovic V, Duckworth CA, Luu L, Wastling J, Derricott H, Coombes JL. A novel in vitro model of the small intestinal epithelium in co-culture with ‘gut-like’ dendritic cells. Discov Immunol. 2023 Oct 7;2(1):kyad018
https://pmc.ncbi.nlm.nih.gov/articles/PMC10917230/
2. Gall L, Jardi F, Lammens L, Piñero J, Souza TM, Rodrigues D, Jennen DGJ, de Kok TM, Coyle L, Chung SW, Ferreira S, Jo H, Beattie KA, Kelly C, Duckworth CA, Pritchard DM, Pin C. A dynamic model of the intestinal epithelium integrates multiple sources of preclinical data and enables clinical translation of drug-induced toxicity. CPT Pharmacometrics Syst Pharmacol. 2023 Oct;12(10):1511-1528.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10583244/
3. 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 Jan;97(1):235-254.
https://link.springer.com/article/10.1007/s00204-022-03374-3
4. 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://pmc.ncbi.nlm.nih.gov/articles/PMC7215182/
5. 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 Nov 26;10(12):896.
https://pmc.ncbi.nlm.nih.gov/articles/PMC6879761/
6. Derricott H, Luu L, Fong WY, Hartley CS, Johnston LJ, Armstrong SD, Randle N, Duckworth CA, Campbell BJ, Wastling JM, Coombes JL. Developing a 3D intestinal epithelium model for livestock species. Cell Tissue Res. 2019 Feb;375(2):409-424.
https://pmc.ncbi.nlm.nih.gov/articles/PMC6373265/