GW4 BioMed3 MRC DLP PhD project: Decoding the Cellular Origin of Barrett’s Metaplasia Using Microlasers and Lab-on-a-Chip Technologies

About the project

About the Project This project is one of several in competition for funding from the GW4 BioMed3 MRC Doctoral Landscape Programme (DLP), which is offering up to 17 studentships for entry in September 2027. The partnership brings together the Universities of Bath, Bristol, Cardiff and Exeter to develop the next generation of biomedical researchers. Students will have access to the combined research strengths, training expertise and resources of the four research-intensive universities. More information may be found on the DLP’s website . Please note that the application process may close early to either home or international candidates (or both) before the stated deadline if an unprecedented number of applications are received – check the DLP’s website for details and updates. Supervisory Team: Dr Soraya Caixeiro (Bath), Prof David Tosh (Bath) and Dr Fabrice Gielen (Exeter) The Project : Barrett’s Metaplasia (BM) is the only established precursor to oesophageal adenocarcinoma, a malignancy with a dismal prognosis and rapidly increasing incidence in Western populations. BM arises in the setting of chronic Gastro-Oesophageal Reflux Disease, where the normal oesophageal stratified squamous epithelium (SSQE) is replaced by intestinal-like columnar epithelium (ICE). Despite its clinical importance, the cellular switch remains unresolved, hindering understanding of disease pathology and the development of early diagnostics and targeted therapies. Several mechanisms have been proposed: (i) stem cell migration from the squamocolumnar epithelium (between the oesophagus and the stomach) to repair the damage caused by acid and bile reflux, thus converting to ICE and (ii) direct transdifferentiation of cells in the SSQE to ICE. However, distinguishing between these possibilities requires high resolution tools capable of tracking individual cell fates and molecular changes in a physiologically relevant context. This project will address this challenge by combining stem cell-derived organoid models, microlaser-based lineage tracing, microfluidics, imaging, and single-cell analysis to identify the cellular origins of BM. Three-dimensional epithelial organoids representing both oesophageal squamous epithelium and squamocolumnar junctional epithelium, the two leading candidate tissues of origin, will provide a physiologically relevant platform in which cellular responses to disease-relevant stimuli can be studied. A key innovation of the project is the use of intracellular microlasers for lineage tracing. These micron-sized optical devices can be internalised by cells and emit highly stable spectral signatures that act as unique optical barcodes. As thousands of distinct signatures can be generated, individual cells and their progeny can be tracked through multiple rounds of cell division. Microlaser integration, previously demonstrated in other organoid systems, will be adapted for epithelial organoids to enable continuous monitoring of cell proliferation, migration, and lineage relationships during disease progression. To model disease initiation, organoids will be exposed to molecular and environmental drivers associated with BM, including bile acid exposure to mimic chronic reflux injury and modulation of key transcriptional regulators. The behaviour of microlaser-labelled cells will be monitored alongside immunostaining of lineage-specific and early metaplastic markers, providing a unique opportunity to identify which cell populations acquire disease-associated characteristics and how these changes propagate through the tissue. To link lineage history with molecular identity, a bespoke lab-on-a-chip platform will be developed for high-throughput single-cell analysis. Following induction of BM-like changes, organoids will be dissociated and analysed using droplet microfluidics integrated with optical spectroscopy. Cells will be isolated according to their microlaser signatures and phenotypic markers, enabling downstream gene expression analysis of populations with distinct developmental trajectories. By combining lineage tracing with molecular profiling, the project will reveal transcriptional programmes associated with the earliest stages of metaplastic transformation. The resulting imaging, behavioural, and transcriptomic datasets will be integrated to reconstruct cellular trajectories and identify the earliest events that commit cells towards a Barrett's-like phenotype. These findings will provide new mechanistic insight into disease initiation and help resolve the long-standing question of the cellular origin of Barrett's Metaplasia. The student will play a central role in shaping the direction of the project. Supported by an interdisciplinary supervisory team with expertise spanning stem cell biology, photonics, microfluidics, and computational analysis, they will be encouraged to develop their own research questions, refine experimental approaches, and contribute to emerging opportunities as the project evolves. Requirements: Applicants must have obtained, or be about to obtain, a first or upper second-class UK honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of medical sciences, computing, mathematics or the physical sciences. Applicants with a lower second-class degree will only be considered if they have a grade of Merit or above in a master’s degree. Academic qualifications are considered alongside significant relevant non-academic experience. Non-UK applicants will also be required to have met the English language entry requirements of the University of Bath. Enquiries and Applications: Informal enquiries are welcomed and should be directed to Dr Soraya Caixeiro https://researchportal.bath.ac.uk/en/persons/soraya-caixeiro/ on email address scc201@bath.ac.uk . Formal applications must be submitted direct to the GW4 BioMed3 DLP using their online application form . A list of all the projects and details on how to apply are available DLP’s website . You may apply for up to 2 projects and submit one application per candidate only. APPLICATIONS CLOSE AT 17:00 (GMT) ON 21 OCTOBER 2026. IMPORTANT: You do NOT need to apply to the University of Bath at this stage – only those applicants who are successful in obtaining an offer of funding from the DTP will be required to submit an application for an offer of study from Bath. Equality, Diversity and Inclusion: We value a diverse research environment and aim to be an inclusive university, where difference is celebrated and respected. We welcome and encourage applications from under-represented groups. If you have circumstances that you feel we should be aware of that have affected your educational attainment, then please feel free to tell us about it in your application form. The best way to do this is a short paragraph at the end of your personal statement.

Research areas