Understanding the DNA damage response network to improve future therapies for glioblastoma

Primary glioblastoma is an incurable cancer that is responsible for over 200,000 deaths/year worldwide with no new treatment strategies or improvements in patient survival rates for decades. The current standard-of-care (SoC) treatment for primary glioblastoma following maximal safe surgical reaction involves the use of radiotherapy and chemotherapy. Given that all these modalities cause DNA damage and/or replication stress, a comprehensive understanding of the DNA damage response (DDR) network within these tumours could identify new treatments. To facilitate this, we have developed the ‘Sheffield Living Biobank’, which currently consists of over 165 glioma stem cell models to recapitulate features of intra-tumoural heterogeneity. The student will join our research team and take part in our ongoing molecular and bioinformatic characterisation of these models as we try to resolve the mechanisms by which spatially mediated heterogeneity within the DDR of GSC niches shapes resistance to standard-of-care radio-chemotherapy, and how we might apply this knowledge to identify and develop new treatment strategies that possess potential pan-tumour efficacy. Students will need to find their own accommodation and be expected to present their findings orally at a research day in York on 08th September 2026.