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Resolving the Associations Between Multicellular Ecosystems and Aggressive Molecular and Evolutionary Tumour States
Secondary Supervisor(s): Professor Dean Fennell, Professor Hongji Yang
University of Registration: University of Leicester
BBSRC Research Themes:
Project Outline
Why do some tumours become more aggressive or respond differently to treatment? The answer may lie not only in tumour cells, but also in the immune and stromal cells around them. This PhD will study these local communities as tumour ecosystems and ask how their organisation is linked to tumour evolution, molecular states and treatment response.
The project will address this broader cancer question through the malignant pleural mesothelioma scenario. The project will design the framework for transfer to other cancer types. The existing materials have matched H&E whole-slide images, pathology reports, genomic, DNA methylation, gene-expression and treatment-response data. This allows direct comparison of tissue organisation with molecular activity and treatment response.
The student will first map tumour, immune and stromal communities across whole slides. They will then develop interpretable AI models that connect these maps with molecular and evolutionary states, and test whether disease states and treatment-response patterns can be inferred from tissue structure. Patient-level and within-tumour comparisons will test robustness, followed by pathologist review and targeted tissue validation.
The project will deliver a spatial atlas of mesothelioma ecosystems, a transferable analysis framework, and interpretable models evaluated on molecular subtyping, progression assessment and treatment-response prediction. It will also produce a prioritised set of ecosystem biomarkers and biological pathways, with the strongest candidates tested in tissue where feasible. These outputs could support diagnostic assessment, guide molecular testing and patient stratification, and identify treatment-linked mechanisms for therapeutic validation. The student will gain integrated training in tumour biology, spatial pathology, multi-omics, quantitative modelling and responsible AI.