Defining the biology of infant ependymoma to identify new treatment targets

About the project

About the Project Ependymoma is the second most common malignant brain tumour of childhood, and infants under three years have among the worst outcomes of all. The very youngest infants cannot safely receive radiotherapy, chemotherapy offers limited benefit, and no proven targeted treatments exist. The high-risk chromosomal gains and losses that explain aggressive disease in older children are much less frequent in infants, so why infant tumours can behave so aggressively remains unknown. This PhD is a discovery study which sets out to answer that question. Preliminary evidence indicates that infant ependymomas are genomically quiet yet developmentally and epigenetically distinct. The student will define what makes these tumours different and identify the biological vulnerabilities that future, less toxic treatments could target. The project is associated with the BIOlogical Markers of Ependymoma in Childhood and Adolescence (BIOMECA) study, the international discovery and validation biological programme embedded within the SIOP Ependymoma II trial, giving access to a well-characterised sample cohort with linked molecular, imaging and clinical data. The student will define the infant tumour's developmental and molecular state using DNA methylation, copy-number, and gene-expression data integrated across BIOMECA and published cohorts. They will map the tumour microenvironment through multiplex immunofluorescence and other methods on archival tissue, supported by immune deconvolution of expression data, relating this to molecular profiling findings. Findings will be integrated with linked imaging and clinical outcomes to produce a ranked set of infant-specific treatment-target hypotheses, with at least one orthogonal line of validation for the leading candidate. Presenting and publishing the work is central throughout. We are looking for a quantitative or molecular-biology graduate with a good honours degree (2:1 or above) and/or a master's in a relevant science - bioinformatics, computational biology, genetics, molecular or cell biology, or biomedical science. Programming and statistics for biological data (R and/or Python), and confidence handling and quality-controlling large datasets, are essential, as is evidence of independent research and the ability to work with complex, imperfect real-world data. Experience with methylation-array or RNA-seq analysis, single-cell methods, or wet-lab techniques (nucleic acid extraction, qPCR, IHC/IF) is welcome but not required, as is prior exposure to neuro-oncology, paediatric or cancer biology. The successful candidate will communicate well across laboratory, bioinformatics and clinical settings, be self-motivated and comfortable with a project that evolves as findings emerge, and be genuinely committed to its translational, patient-facing purpose. The student will be based in the Children's Brain Tumour Research Centre at the University of Nottingham, embedded in an established team with national and international collaborations. Supervision spans clinical paediatric neuro-oncology and tumour biology, laboratory science and neuroimaging, so a candidate strong in one domain will be supported to develop the others. Training covers molecular and computational methods, spatial tissue analysis, research communication, and good clinical and laboratory practice, with regular lab meetings and structured PhD oversight and annual review.

Research areas