The PhD will be based in the School of Pharmacy and Biomedical Sciences and will be supervised by Dr Helen L Fillmore and Dr Frank Schubert.
The work on this project could involve:
● Human cell and organoid cultures
● Animal models of DIPG
● Bioinformatics analyses, validation using pathological methodology
● Applying molecular genetics techniques to understand mechanisms of cancer growth
● Single cell RNA sequence analysis
● Functional assays
Project description
This project is part of Dr Fillmore’s research programme in understanding host/tumour microenvironment in CNS cancers and its importance for advancing treatment strategies. The focus of this project will be in the area of the developing brainstem and its intersection with high-grade paediatric brainstem gliomas, sometimes referred as diffuse intrinsic pontine gliomas (DIPG). An exciting and promising (therapeutic) area of interest based on preliminary data is the potential involvement of the sphingolipid metabolism and sphingosine 1-phosphate (S1P) signalling pathway in DIPG. The S1P pathway comprises an interacting network of metabolic enzymes, receptors, transporters, and epigenetic partners. Its association with several of the cancer hallmarks, and its important role in regulation of PHB2, a key component and stabiliser of the inner mitochondrial membrane, as well as its role in myelination and diseases such as multiple sclerosis provide the background and rationale for this project. S1P, a critical component of the “sphingolipid rheostat”, is known for its ‘inside out signalling’, 2nd messenger signalling in response to specific growth factors and can act as an autacoid. Preliminary data indicate that the SP1-producting kinase Sphk2, but not Sphk1, is decreased in DIPG. Analyses of single cell RNAseq data revealed that SPHK2 is associated with microglia and OPCs whereas other associated genes are expressed in endothelial and pericyte cells which is reasonable given S1Ps role in immune response, vascular stability, cell proliferation and differentiation. The underlying hypothesis is that the S1P pathway is disrupted in DIPG tumour microenvironment and may play a contributing role in the pathobiology. The project aims are: 1. Validate dysregulation of S1P in DIPG in vitro. 2. Characterise the S1P biosynthesis and signalling pathway in brainstem development. 3. Test the role of the S1P pathway in brain development and in DIPG.
General admissions criteria
You'll need a good first degree from an internationally recognised university (minimum upper second class or equivalent, depending on your chosen course) or a Master’s degree in an appropriate subject. In exceptional cases, we may consider equivalent professional experience and/or qualifications. English language proficiency at a minimum of IELTS band 6.5 with no component score below 6.0.
Specific candidate requirements
The project would suit a science graduate with experience in molecular techniques, cell culture, animal studies, the ability to work across disciplines, and the willingness to interact with stakeholders and the public.
A full programme of training courses is provided to graduate students by the Graduate School. The successful candidate will also have the opportunity to undergo in-house training for a variety of instruments and techniques essential to the project, as well as the opportunity for additional training at partner institutions.
How to Apply
We’d encourage you to contact Dr Helen L Fillmore ([Email Address Removed]) to discuss your interest before you apply, quoting the project code.
When you are ready to apply, you can use our online application form. Make sure you submit a personal statement, proof of your degrees and grades, details of two referees, proof of your English language proficiency and an up-to-date CV. Our ‘How to Apply’ page offers further guidance on the PhD application process.
If you want to be considered for this funded PhD opportunity you must quote project code PHBM6321021 when applying.
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