Fixed-term

Details Pancreatic ductal adenocarcinoma (PDAC) has a low survival rate and new therapies are urgently needed. The RhoGEF, Ect2, is frequently overexpressed in PDAC tumours and is associated with a poor prognosis. Ect2 modulates the contractility of the actin cytoskeleton by locally activating RhoA and plays a role in multiple cellular processes including cell division, DNA repair and cell migration. However, it’s not clear which of these roles are most important for its function in PDAC tumorigenesis. In addition, Ect2 is regulated by the YAP/TAZ mechano-sensitive signalling pathway and our preliminary data indicate that its subcellular localisation is altered when cells are grown on stiffer substrates. This is likely to have implications for proliferation of cancer cells within PDAC tumours, which are mechanically extremely stiff. This project will investigate the role of Ect2 mechano-sensing in pancreatic cancer cells and patient tumours. Specifically, this project aims to: 1. Characterise the effect of Ect2 depletion on PDAC cell proliferation, division and migration 2. Understand how mechanosensitive signalling regulates Ect2 localisation and activity 3. Image the localisation of Ect2 in PDAC patient tumours The project will use a combination of cell and molecular biology approaches (including CRISPR gene editing, western blotting, flow cytometry), advanced microscopy (live cell imaging & immunofluorescence) and histopathological staining of patient samples to elucidate the role of Ect2 in PDAC. To investigate the mechano-regulation of Ect2, cells will be grown on soft and stiff hydrogels to mimic the increasing tissue rigidity within PDAC tumours. Ultimately, this project aims to develop Ect2 as a potential new target for PDAC therapy. Lab website: https://www.helenmatthewslab.org/ Please apply for this project using this link: https://www.sheffield.ac.uk/postgraduate/phd/apply/applying Funding Notes Externally or self-funded students only Apply Now

Details Epithelial tissues are characterised by the expression of keratin proteins, which assemble into flexible, unbranched filaments to create complex cytoplasmic networks. These networks span across multiple cells, providing structural rigidity and allowing tissues to withstand mechanical forces. Keratins are less studied compared to other cytoskeletal filaments and their role in dictating the material properties of tissues and response to forces in proliferative tissues remains poorly understood. Abnormal keratin expression during cancer development can alter tissue mechanical properties and allow cancer cells to withstand compressive forces within a tumour environment. This PhD project aims to map keratin network architecture in epithelial monolayers and understand how they are reorganised in response to tissue stresses and during cancer development. Specifically, this project aims to: 1. Map keratin network architecture at super resolution in epithelial monolayers 2. Understand how keratin networks respond to local and tissue-scale forces 3. Understand how changes in keratin expression in cancer alter network organisation and response to force. This project will use state-of-the-art live-cell super resolution microscopy and automated image analysis to both visualise the 3D architecture of keratin networks in epithelial monolayers. You will explore how these networks influence tissue mechanical properties across scales and investigate their response to both local forces induced by cell divisions and tissue-scale stresses. You will then investigate how networks are altered following keratin switching in pancreatic cancer and whether this affects the ability of cells to withstand compressive forces using a mechanical confinement assay. This highly interdisciplinary project would suit a student with a background in either biophysics or biosciences, who is keen to develop skills in microscopy, quantitative image analysis and biophysical techniques. You will work together with a dynamic and friendly team of researchers across two different laboratories including cell biologists, biophysicists and computational experts. This project will give you the opportunity to develop cutting-edge imaging and analytical tools to answer fundamental biological questions about how tissues and tumours respond to mechanical stresses. Lab website: https://www.helenmatthewslab.org/ Please apply for this project using this link: https://www.sheffield.ac.uk/postgraduate/phd/apply/applying Funding Notes Externally or self-funded students only Apply Now

Details Cancer metastasis accounts for around 90% of cancer deaths. While the survival rate has been improved over the years through early diagnosis, limited progress has been made in the targeting of metastasis. This stems from a fundamental lack of understanding of the basic biology underlying this process. While flies have emerged as powerful tool to investigate tumour growth and identify cancer related pathways, to-date studies have been limited by a lack of metastatic models where cells can be followed from primary tumour development to secondary tumour formation in adult organisms. We recently overcame this longstanding limitation, developing the first model for the induction of macrometastases in adult Drosophila melanogaster. This project aims to now leverage this model to identify the cellular and molecular mechanisms that underlie the first steps of cell dissemination from the primary tumour. This will involve developing methods to live image tumour cell dissemination from primary tumours, and out of a complex organ, on our labs own dedicated multiphoton confocal. In parallel, genomics data existing within the lab will be mined to identify candidate genes. Combining live and fixed confocal analysis, as well as sensitive luciferase assays for each step of the metastatic process, these candidates will be investigated for a functional role in tumour metastasis. Overall, we expect the findings from the project to provide new insight into the complex process of cancer metastasis, as well as provide novel prognostic and therapeutic markers for metastatic colorectal cancer. Funding Notes Self-funding applicants only. References “Lab website https://cellplasticity.weebly.com/publications.html Recent publications from the lab Plygawko, A.T., Adams, J., Richards, Z. and Campbell, K. (2025) A hormonally regulated gating mechanism controls EMT timing to ensure progenitor specification occurs prior to epithelial breakdown. BioRxiv. doi: 10.1101/2025.07.19.665116 Montes-Labrador, M., Campbell, K. and Casali, A. (2025) Drosophila as a model for metastasis. Advances in Experimental Medicine and Biology. doi: 10.1007/978-3-031-97035-1_8. Jonckheere, S., Taminau, J., Adams, J., Haerinck, J., De Coninck, J., Verstappe, J., De Clercq, K., Peeters, E., Gheldof, A., De Smedt, E., Goossens, V., Audenaert, D., Candi, A., Versele, M., De Groote, D., Verschuere, H., Stemmler, M., Brabletz, T., Vandenabeele, P., Casali, A., Campbell, K., Goossens, S. and Berx, G. (2025). Development and validation of a high-throughput screening pipeline of compound libraries to target EMT. Cell Death and Differentiation. doi: 10.1038/s41418-025-01515-6. Plygawko, A.T, Stephan-Otto Attolini, C., Pitsidianaki, I., Cook, D.P., Darby, A.C and Campbell, K. (2024) The Drosophila adult midgut progenitor cells arise from asymmetric divisions of neuroblast-like cells. Developmental Cell. doi: 10.1016/j.devcel.2024.10.011 Parisi, E., Hidalgo, I., Montal, R., Pallisé, O., Tarragona, J., Sorolla, A., Novell, A., Campbell, K., Sorolla, M.A., Casali, A. and Salud, A. (2023) PLA2G12A as a novel biomarker for colorectal cancer with prognostic relevance. International Journal of Molecular Sciences. doi: 10.3390/ijms241310889. Sharpe, J.L., Morgan, J., Nisbet, N., Campbell, K. and Casali, A. (2023) Modelling cancer metastasis in Drosophila melanogaster. Cells. doi: 10.3390/cells12050677. Jonckheere, S., Adams, J., De Groote, D., Campbell, K., Berx, G. and Goossens, S. Epithelial-Mesenchymal Transition (EMT) as a therapeutic target. (2022) Cells Tissues Organs. doi: 10.1159/000512218 Pitidianaki, I., Morgan, J., Adams, J. and Campbell, K. (2021) Mesenchymal-to-epithelial transitions require tissue-specific interactions with distinct laminins. Journal of Cell Biology. doi: 10.1083/jcb.202010154 Adams, J., Casali, A. and Campbell K. (2021) Sensitive high-throughput assays for tumour burden reveal the response of a Drosophila melanogaster model of colorectal cancer to standard chemotherapies. International Journal of Molecular Sciences. doi: 10.3390/ijms22105101” Apply Now

Details Cells in development are constantly on the move — migrating to new locations, changing shape, and coordinating with their neighbours. But at some point, migratory cells must stop, polarise, and assemble into epithelial sheets to form organised tissues. How do cells decide when to make this transition from migration to building tissues, and how do their orientate and coordinate their behaviour with respect to their position in the embryo? This PhD project will focus on dissecting the external and internal factors driving a cell to stop moving become epithelial, guiding this fundamental switch during Drosophila midgut morphogenesis. You will use either existing single-cell transcriptomic atlases within in the lab, or carry out new single cell RNA-seq experiments to identify candidate pathways. You will then investigate for a functional role using deep-tissue live and fixed imaging on our lab’s own dedicated dual-line multiphoton confocal combined with cell and genetic approaches routinely performed in the lab, such as FISH and CRISPR. There will also be the chance to build on techniques we have recently started using in our system, such as expansion microscopy and laser ablation combined with live imaging. This is a unique opportunity for you to carry out cutting-edge microscopy and develop your skills in an exciting multidisciplinary environment. Funding Notes Self-Funded applicants only References “Lab website https://cellplasticity.weebly.com/ Recent work from the lab Plygawko, A.T., Adams, J., Richards, Z. and Campbell, K. (2025) A hormonally regulated gating mechanism controls EMT timing to ensure progenitor specification occurs prior to epithelial breakdown. BioRxiv. doi: 10.1101/2025.07.19.665116 Plygawko, A.T, Stephan-Otto Attolini, C., Pitsidianaki, I., Cook, D.P., Darby, A.C and Campbell, K. (2024) The Drosophila adult midgut progenitor cells arise from asymmetric divisions of neuroblast-like cells. Developmental Cell. doi: 10.1016/j.devcel.2024.10.011 Sharpe, J.L., Morgan, J., Nisbet, N., Campbell, K. and Casali, A. (2023) Modelling cancer metastasis in Drosophila melanogaster. Cells. doi: 10.3390/cells12050677. Jonckheere, S., Adams, J., De Groote, D., Campbell, K., Berx, G. and Goossens, S. Epithelial-Mesenchymal Transition (EMT) as a therapeutic target. (2022) Cells Tissues Organs. doi: 10.1159/000512218 Pitidianaki, I., Morgan, J., Adams, J. and Campbell, K. (2021) Mesenchymal-to-epithelial transitions require tissue-specific interactions with distinct laminins. Journal of Cell Biology. doi: 10.1083/jcb.202010154 Plygawko, A.T., Kan, S., and Campbell, K. (2020) Epithelial–mesenchymal plasticity: emerging parallels between tissue morphogenesis and cancer metastasis. Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 375, No. 1809. doi: 10.1098/rstb.2020.0087. Apply Now

Details The project will use genomic and epigenetic datasets to address evolutionary questions in one of the best-studied wild mammal populations anyway in the world – the Soay Sheep population of St Kilda, Scotland. There is considerable flexibility to propose and develop a research question, with support from the supervisor. Most of our work combines genomic, epigenetic and life history data to try to tease apart the effects of genes and environment on phenotypic variation. We have recently developed an interest in epigenetic clocks as tools to understand ageing and the effects of environmental variation on traits related to fitness and survival. There will be the possibility of carrying out field work on St Kilda, as well as labwork opportunities. An interest in exploring, analysing and interpreting genomics datasets is a necessity, although training on that will be given. Science Graduate School As a PhD student in one of the science departments at the University of Sheffield, you’ll be part of the Science Graduate School. You’ll get access to training opportunities designed to support your career development by helping you gain professional skills that are essential in all areas of science. You’ll be able to learn how to recognise good research and research behaviour, improve your communication abilities and experience the breadth of technologies that are used in academia, industry and many related careers. Visit http://www.sheffield.ac.uk/sgs to learn more. Funding Notes First class or upper second 2(i) in a relevant subject. To formally apply for a PhD, you must complete the University’s application form using the following link: https://www.sheffield.ac.uk/postgraduate/phd/apply/applying All applicants should ensure that both references are uploaded onto their application as a decision will be unable to be made without this information. References Jon Slate: https://www.sheffield.ac.uk/biosciences/people/academic-staff/jon-slate Soay Sheep Project: https://biology.ed.ac.uk/soaysheep Apply Now

Details The surface of cancer cells is a unique environment to study, as it is the gatekeeper for the uptake of nutrients and drugs. The turn-over and organisation of proteins at the plasma membrane is an essential part of cellular regulation. Many cell surface proteins have been implicated and play a role in disease progression. Using an siRNA targeted screen for novel drug uptake mechanisms, we have identified a class of receptors enriched on the surface of cancer cells that appear to also play a role in metabolic regulation. Little is known about some of these receptors or how and why their expression is unregulated. However, clinical reports suggest that higher expression in patients leads to a poor prognosis. Our group is highly invested in understanding their molecular and cellular biology. This project will investigate the expression, internalisation and signalling of these membrane proteins. We would like to investigate these as potential new cancer targets for drug discovery. This PhD will investigate the role of these receptors in cancer growth and progression using microscopy, cellular and molecular techniques. You will gain hands-on expertise in cutting-edge techniques, including: advanced cell microscopy at the Wolfson Light Microscopy Facuilty, using confocal and super-resolution (SIM and STORM) systems, alongside data analysis tools and expert scientific support. You will use quantitative cellular assays, and sophisticated molecular biology tools creating receptor mutants using CRISPR and knock-downs with siRNA. We’re seeking a highly motivated and curious scientist with a strong foundation in Pharmacology, Biochemistry, Cell Biology, or Molecular Biology. If you are passionate about translational science and want your research to have a tangible impact on the fundamental science underpinning human health please contact us. The School of Biosciences at the University of Sheffield hosts ~240 PhD students and you’ll be based in the Molecular and Cellular Biology Research Cluster. You’ll get access to professional training opportunities designed to support your career development, including communication and technology skills that are essential in academia, and industry. Visit http://www.sheffield.ac.uk/sgs to learn more. Funding Notes Please note this is for Self-Funded students only References Hadianamrei R, et al., (2023) Biochem Biophys Res Commun. doi: 10.1016/j.bbrc.2023.02.026 Cirillo S, et al., (2024) Eur J Pharm Biopharm. doi: 10.1016/j.ejpb.2024.114244 Brown Laboratory https://sheffield.ac.uk/biosciences/people/academic-staff/stephen-brown