Developing 3D-Bioprinted Constructs to Model the Tumour-Brain Interface in Glioblastoma
Primary Supervisors: Dr Lucy Books
Second Supervisor: Professor Puneet Plaha
Project Overview
Glioblastoma (GBM) is the most common intrinsic malignant primary brain tumour in adults, with an average survival of ~1 year. This poor prognosis reflects the tumour’s pronounced resistance to surgery, chemotherapy, and radiotherapy. Even with optimal treatment, GBM almost invariably recurs due to the persistence of tumour cells that evade removal and withstand adjuvant therapy. Understanding the biology of these residual cells is critical to preventing relapse. Because of the delicate and highly integrated nature of the brain, complete surgical removal of all tumour cells is impossible without unacceptable damage. Residual cells embedded in surrounding brain tissue drive recurrence, with ~90% of relapses occurring within 2cm of the surgical margin. This region is clinically significant but challenging to study due to limited access to relevant patient material and the lack of laboratory models that fully capture its cellular and microenvironmental complexity. This interdisciplinary project combines unique clinical access to patient material with advanced bioengineering and state-of-the-art analytical approaches. In collaboration with neurosurgeon Mr Puneet Plaha, who leads the Awake Surgery Brain Tumour Programme in Oxford, rare tissue samples will be obtained from beyond the tumour core through pioneering supramaximal resections, material enriched for the cells most likely to survive surgery, resist therapy, and drive relapse. Partnering with Dr Linna Zhao (Ludwig Cancer Institute, University of Oxford), an expert in stem cell biology and 3D tissue bioengineering, patient-derived cells will be incorporated into 3D-bioprinted tumour–brain constructs that recreate the architecture, cellular diversity, and microenvironment of the tumour margin. Live imaging, single-cell profiling, and functional assays will be used to refine these models and investigate how therapy-resistant cells adapt and survive. 3D-bioprinted tumour–brain constructs will provide a pathologically relevant platform for mechanistic studies of tumour persistence and therapy resistance, enabling development of strategies to eliminate resilient GBM cell populations.
Training Opportunities
This project offers broad interdisciplinary training spanning cancer biology, stem cell and tissue engineering, and advanced analytical techniques. Laboratory skills will include primary culture of iPSCs and patient-derived cells, 3D tissue bioengineering, and co-culture systems to model tumour–microenvironment interactions. The student will also learn live imaging, quantitative image analysis, CRISPR-Cas9 genome editing, and single-cell technologies such as mass cytometry. Bioinformatics training will cover processing, integration, and visualisation of complex datasets from imaging and single-cell profiling. The student will actively engage in seminars and journal clubs, present at internal meetings, and have opportunities to share their findings at national and international conferences, strengthening scientific communication and professional skills. They will also be encouraged to attend specialist skills workshops throughout the PhD to broaden their expertise.
References
Brooks, L.J., Ragdale, H.S., Hill, C.S., Clements, M. and Parrinello, S., 2022. Injury programs shape glioblastoma. Trends in Neurosciences, 45(11), pp.865-876.
https://www.cell.com/trends/neurosciences/fulltext/S0166-2236(22)00163-1