Sweet Signals: Examining the impact of O-GlcNAc on estrogen responses in breast cancer

The estrogen receptor (ER) is a ligand-activated transcription factor that drives the growth of ~80% of breast tumours. Although most ER-positive breast cancers initially respond well to endocrine therapies, resistance emerges in one-third of patients, presenting a major unmet clinical need. ER is rarely mutated during tumour formation; rather, carcinogenesis is driven by rewiring ER transcriptional programmes. One such modification, O-GlcNAcylation, is under-researched in breast cancer. Consequently, regulation of O-GlcNAc represents a novel strategy for targeting endocrine therapy resistance. This project aims to examine the impact of O-GlcNAcylation on the ER transcriptome. Building on existing RNA-seq data from ER-positive breast cancer cells, the student will investigate O-GlcNAc-dependent changes in estrogen signalling. This will involve first building skills in cell culture and gene expression analysis, and then undertaking phenotypic assays, qPCR, and finally integration of this phenotypic and bioinformatical data. This project will provide the selected student with hands-on bioinformatics and wet-lab training, alongside addressing potential mechanisms behind endocrine therapy resistance. 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.