Paediatric diffuse midline glioma (PDMG, previously Diffuse intrinsic pontine glioma, DIPG) is an incurable aggressive brain tumour, differing from glioblastoma multiforme (GBM) in terms of genetics and microenvironment, with 90% of children diagnosed surviving less than 2 years. Due to their brain-stem location and invasive behaviour, surgery is not an option, and radiation therapy is currently the standard of care with transient improvement. Standard chemotherapies and new biological inhibitors either alone or in combination with radiation have not translated into survival improvement and the quality of life for these children is very poor. These statistics have not changed in decades, therefore there is a great need to identify novel targeted and less toxic treatment strategies.
‘Tumour treating fields’ (TTF) has recently emerged as a fourth method (after surgery, chemo and radiotherapies) for treating cancer, where intermediate frequency electric fields applied across a tumour have been found to inhibit tumour growth. A recent large international phase III trial comparing NovoCure’s TTF in conjunction with Temozolomide chemotherapy vs. chemotherapy alone was terminated early due to a surprising three-month increase in overall survival. Paediatric gliomas, molecularly distinct from adult GBM and are surrounded by developing nervous tissue. Existing TTF approaches are unable to focus the field sufficiently to kill tumour cells within a developing brain. In collaboration with electrical engineers at Plymouth University Peninsula Schools of Medicine and Dentistry (PUPSMD), we are developing a novel 3D field generation system based on magnetic fields to focus electric fields as a non-invasive treatment modality for this cancer.
The aim of this project is to conduct fundamental cellular and molecular level studies that are necessary to determine the potential of TTF to treat PDMG cells. These will include tumour cell growth and migration studies across electric and magnetic fields, using well-characterised cell viability/clonogenic assays and live cell imaging, building upon our preliminary experiments, resulting in the first detailed investigation into how cancerous and healthy cells respond to varying field strengths. We will work closely with our collaborators at PUPSMD, who bring their electromagnetics and physical sciences expertise to the project. The second part of the programme will the development of 2D and 3D TTF systems (the latter using ‘pseudo heads’) to treat cells and we expect during this time, substantial funding (CwCUK, CRUK or BBSRC) will be secured to go beyond ‘proof-of-concept’ to fully test this technology, which could potentially revolutionise therapies particularly for PMDG.
The project will be accommodated within the Cellular and Molecular Neuro-oncology Research Group, Institute of Biomedical and Biomolecular Sciences (IBBS). The student will be trained in a number of techniques including tissue culture, fluorescence microscopy, live cell imaging and flow cytometry. The project will be carried out with our collaborative partners at the University of Plymouth.
In addition you will have access to a skills development programme run by the University’s Graduate School. The experimental and analytical skills developed during this project will prepare the student well for a future career in academia or industry.
This self-funded PhD project can be accommodated either full-time (3 years) or part-time (max 6 years, but likely to be completed in less time). If run part-time, the applicant must be available to carry out laboratory work at the University during their studies (for a mutually agreed period). Therefore non-EU/UK students can only be considered on a full-time registration basis.
PhD projects usually commence in October or February each academic year, but can start a month later if appropriate.
Please email me to express and interest or if you have any queries ([email protected]
For more information:
Research Group Web Site http://www.port.ac.uk/school-of-pharmacy-and-biomedical-sciences/research/
Own website: http://www.jamesrsmith.net
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Self funded - University tuition fees, Full-time: currently, £13,100 per annum for International Students and £4,052 pa for Home and EU students; Part-time: UK/EU fees approx. £1,500 pa. Projects will need to be self-funded with a bench fee (consumables) at £3000 pa (full-time rate, and pro rota for part-time).