Role of Extracellular Matrix in Hypoxic Metastasis

The extracellular matrix plays a vital role in the local tumour microenvironments modulating both physical properties and molecular features. The glycosaminoglycans are polysaccharide chains and arguably the most dynamic of the extracellular matrix components. There are relatively few glycosaminoglycans but include heparan sulphate, chondroitin sulphate and hyaluronan.

Most importantly the biological complexity of the polysaccharide chains depends on their post translation modifications. These modifications can significantly alter cell phenotypes hence implications for functional changes during development, in tumours, or during ischemia are wide reaching.

The project partners the University of Nottingham's "GlycoWeb" funding novel glycosaminoglycan analysis and detection techniques. This fundamental doctoral training program position will use those novel techniques to study the underpinning tumour microenvironment on a cellular scale. We will test the hypothesis that the metastatic cells within a tumour have a different glycosaminoglycan profile to the surrounding cells enabling both proliferation and migration from the tumour.

The project aims to initially understand cellular response using 2D (gene edited) models and then transfer this to 3D models using a hydrogel system developed by our industrial partners. The successful student will then develop 3D correlative imaging techniques based around a multiphoton fluorescent map of the 3D culture before beyond state-of-the-art analysis techniques for GAGs including spatial transcriptomics/metabolomics and imaging mass spectrometry.