A fully funded four-year PhD studentship is available at Sheffield Hallam University within the research group of Dr Lewis Quayle, offered through the BBSRC Yorkshire Bioscience Doctoral Training Partnership (YBDTP). This project investigates the molecular basis of tumour cell dormancy in breast cancer, using an interdisciplinary combination of bioinformatics, systems biology and advanced spatial omics. The project is delivered in collaboration with Dr Nik Georgopoulos (Sheffield Hallam University) and Professor Penelope Ottewell (University of Sheffield). The studentship is open to UK applicants, with the programme beginning in October 2026 and applications closing on 7 January 2026. Background and Research Context Breast cancer is the most common cancer affecting women in the UK, and metastatic relapse remains the leading cause of mortality. Despite successful treatment of primary tumours, some cancer cells persist in a dormant, non-dividing state for years or even decades. These cells can evade therapies designed to target proliferating cells and can later reactivate, causing incurable metastasis. A core challenge in oncology is understanding:• How dormant tumour cells survive long term• What regulates their reversible entry into quiescence• Which signals trigger reactivation and metastatic outgrowth This PhD project aims to identify and characterise the regulatory networks, molecular programmes and microenvironmental interactions that sustain mitotic quiescence, using a combination of computational and experimental approaches. It will contribute to a more complete mechanistic understanding of dormancy and ultimately support strategies to prevent metastatic relapse. Project Objectives and Structure Phase 1: Discovery Through RNA-seq Analysis The student will begin by analysing a unique collection of RNA-seq datasets generated from novel breast cancer dormancy models. Objectives include: Differential expression analysis between dormant and proliferative states Identification of conserved and subtype-specific dormancy signatures Construction of gene regulatory networks linked to mitotic quiescence Use of pathway enrichment and systems biology tools to understand dormancy architecture Integration of multi-omic information to refine mechanistic hypotheses This phase will produce a map of molecular regulators that drive or maintain dormancy across various breast cancer contexts. Phase 2: Spatial Validation Using Xenium Transcriptomics Key findings will be validated using 10x Genomics Xenium spatial transcriptomics, enabling the student to evaluate dormancy mechanisms within their microenvironmental niches. Work will involve: Spatial localisation of regulatory signals identified computationally Characterisation of how dormant tumour cells interact with stromal and immune components Mapping niche signals that support long-term survival Identifying positional factors that may initiate reactivation This spatial layer will help determine how microenvironmental cues reinforce dormancy or prompt escape. Phase 3: Mechanistic Integration and Framework Development The final stage aims to synthesise discovery and validation insights into a coherent mechanistic model. The student will: Build an integrated framework explaining persistence and reactivation Identify potential biomarkers or therapeutic targets to prevent relapse Develop translational insights for future experimental or clinical investigation Training and Skill Development The interdisciplinary nature of the project ensures training across several domains essential for modern bioscience research. The student will gain experience in: High-performance computing and workflow optimisation Bulk and spatial transcriptomic analysis Network biology and algorithmic modelling Multi-omic data integration Principles of cancer dormancy and tumour–host interactions Scientific writing, presentation and cross-disciplinary collaboration They will also join a thriving community of postgraduate researchers and receive tailored training through the YBDTP, which offers: Specialist skills courses Cohort-wide professional development Opportunities for interdisciplinary collaboration across Yorkshire and Teesside universities Supervision and Research Environment The supervisory team offers deep expertise in oncology, multi-omics and computational biology.• Dr Lewis Quayle (SHU): Molecular oncology, systems biology, computational modelling• Dr Nik Georgopoulos (SHU): Cancer cell biology and disease modelling• Prof Penelope Ottewell (University of Sheffield): Metastasis biology and preclinical cancer research Students will benefit from:• Access to specialist computational resources• Established collaborations across institutions• A supportive and highly engaged supervisory team Eligibility Requirements Applicants must meet the following criteria:• Hold or expect to obtain at least an upper second-class honours degree (or equivalent)• Come from a biological, chemical, physical, mathematical or related discipline• Demonstrate interest in applying computational tools to biological questions• Meet English-language requirements (IELTS 7 overall, minimum 6.5 in each component if applicable) The YBDTP encourages applications from individuals of all backgrounds and is committed to inclusive and equitable recruitment. Funding Package This fully funded four-year studentship includes:• A tax-free stipend aligned with either the Real Living Wage (£22,152 for 2025/26) or the UKRI rate (£20,780 for 2025/26), whichever is higher• Coverage of UK-rate tuition fees• Support for research and training costs How to Apply • Deadline: 5pm (UK time), Wednesday 7 January 2026• Submit an expression of interest form via the YBDTP portal• Applicants may apply for up to two YBDTP projects• Project enquiries: l.quayle@shu.ac.uk• Application enquiries: YBDTP@leeds.ac.uk Selection Process • Shortlisting occurs soon after the closing date• Interviews take place in February 2026• Applicants will be notified if they are successful, placed on reserve or unsuccessful• Successful applicants must confirm acceptance within 10 days Additional Information Links to supervisor profiles, lab webpages and the YBDTP website are available for applicants seeking more context on the research environment, facilities and training opportunities. 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