The Nottingham BBSRC Doctoral Training Partnership is pleased to be able to offer an opportunity join our programme from October 2022 to work on a fully-funded PhD in the School of Medicine, University of Nottingham, in partnership with the Sam White Legacy - a charity which supports childhood and young adult brain tumour research.
Metabolomic profiling of neurodevelopmental programs in healthy brain which promote cancerous growth
For the malignant brain cancer, ‘glioblastoma’, patients are asymptomatic during early stages of disease, likely explained by cancer cells functionally interacting with healthy neural cells and thereby ‘hiding’. This means that for improved therapy, we need to study how this deadly association promotes phenotypes characteristic of brain cancer.
Recent neuroscientific evidence has revealed that biochemical and electrochemical signalling from the healthy brain, can foster a microenvironment which promotes dysregulated growth. However, the underlying functional relationship remains unclear. Metabolomics is the study of chemical processes involving metabolites and is an integral technology for understanding the function of biological systems. To date, no metabolomic studies have been conducted to elucidate biochemical communication between healthy and cancerous brain cells.
The overarching project hypothesis states that neural communication between healthy astrocytes and dysregulated, transformed neural cells, is characterised by aberrant metabolomic signatures.
You will test this hypothesis by co-culturing 3-dimensional spheroids composed of transgenic glioblastoma patient-derived cells tagged with a fluorescent reporter gene, and human astrocytes from the brain cortex. Spheroids will be placed onto decellularised human (autopsy) brain extracellular matrix to retain physiologically accurate signalling from ligands on the surface of this matrix.
To investigate whether astrocytic-cancerous communication varies during distinct neurodevelopmental states, cells will be maintained in conditions which enrich either neural stem cells or lineage-committed progenitor cells. Upon periods of co-culture, glioblastoma cells and astrocytes will be isolated by fluorescence-activated cell sorting. Liquid-chromatography mass spectrometry will be conducted on each cellular population to reveal metabolomic profiles putatively associated with this biochemical crosstalk. Finally, to validate research findings, metabolomics will be conducted on primary tumour tissue isolated from patients undergoing surgery.
The project involves a multidisciplinary academic and clinical team led by Dr Ruman Rahman and based within the new Biodiscovery Institute, which houses the university’s Centre for Cancer Sciences. You will also be co-supervised by Dr Dong-Hyun Kim with access to the Centre for Analytical Bioscience at the School of Pharmacy, and by Dr Stuart Smith with access to brain tumour tissue derived from the Queen’s Medical Centre, Department of Neurosurgery.
These partnerships will ensure training in molecular biology, mammalian primary cell culture, mass spectrometry, omics data analyses and advanced statistics, all within a clinically relevant context.
This fully funded 4-year PhD studentship is available in the School of Medicine, University of Nottingham. It is jointly funded by BBSRC through the Nottingham BBSRC Doctoral Training Programme, and by the Sam White Legacy, a charity which supports childhood and young adult brain tumour research. Candidates applying for this studentship will not undertake lab rotations, but will start working on this project immediately following DTP induction. You will be expected to complete a 3-month Professional Internship for PhD Students as part of your DTP programme.
Funding is available for four years from late September 2022. The award covers the tuition fee (£4,567) at the home rate plus an annual stipend (£16,062) for 2022. This is set by the Research Councils. Only candidate with UK fees status are currently eligible to apply.
Apply online now.