Role of Extracellular Matrix in Hypoxic Metastasis

Lead Supervisor: Kenton Arkill

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 (PeptiMatrix™). 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. 

The position is based in the University of Nottingham Biodiscovery Institute with four floors of multidisciplinary laboratories and will have team support with cross-school scientific and clinical researchers. We have a strong record in developing and training scientists and this project has an industrial placement to gain non-academic scientific experience. 

Check your eligibility and apply here

 Funding details:

  • This opportunity is open to both Home and International students. Funding is available for four years from October 2024.
  • The award covers tuition fees at the home rate (currently £4712) plus an annual stipend (currently £18,622 for 2023/2024). This is set by the Research Councils. More information about funding is available here.

Biotechnology and Biological Sciences Doctoral Training Programme

The University of Nottingham
University Park
Nottingham, NG7 2RD

Tel: +44 (0) 115 8466946
Email: bbdtp@nottingham.ac.uk