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The role of mitochondrial mutations in the prognosis and treatment of glioblastoma


Project Description

Applications are invited for a fully-funded three year PhD to commence in October 2020.

This fully-funded studentship represents a joint venture between the University of Portsmouth, Liverpool John Moore’s University (LJMU), and Imperial College London (ICL).

The PhD will be based in the Faculty of Science and Health at the University of Portsmouth, and will be supervised by Dr Rhiannon McGeehan, Dr Matthew Guille and Dr Samuel Robson.

The work will include:
- Analysis of next generation sequencing datasets from primary glioblastoma using mtDNA-specific bioinformatics pipelines
- Characterisation of mtDNA genotype-glioblastoma patient survival relationships
- Functional validation of mtDNA genotype-phenotype relationships, including drug sensitivity, using in vitro and in vivo (mouse) models of primary glioblastoma

Glioblastoma is the most common, malignant primary brain tumour in adults, with a dismal prognosis. Genetic markers that successfully inform prognosis and treatments of glioblastoma remain limited with little improvement in survival being achieved over the last 40 years. Studies investigating the DNA of the energy producing mitochondria (mtDNA) are aiming to identify new prognostic and predictive markers for glioblastoma patients.

We have identified an inherited mtDNA mutation enriched in glioblastoma patients relative to healthy controls (1), which is also associated with alterations in mitochondrial activity and mitochondrial-targeted drug sensitivity in vitro in glioblastoma cells. Glioblastoma patients with this mtDNA mutation also had poorer prognosis than non-carriers (2). The student will validate the importance of this inherited mutation further, and extend the investigation to other mtDNA mutations we have discovered through our glioblastoma next generation sequencing studies.

This project will use our expertise in mitochondrial genetics, energy metabolism, bioinformatics, and statistics from within the Institute of Biological and Biomedical Sciences (IBBS), to further our understanding of the role of mtDNA mutations in glioblastoma. Longer-term, we expect mtDNA mutations to have clinical potential, helping personalise effective treatments for glioblastoma patients.

A full program of training will be provided by the Graduate School, as well as specialist training in a range of in-house instruments and techniques available at Portsmouth and collaborating laboratories. There will be transfer of materials (genetic data, DNA samples, and cellular models) and expertise between Portsmouth and collaborator sites, and the opportunity to undertake some training at LJMU and ICL.


General admissions criteria
You’ll need an upper second class honours degree from an internationally recognised university or a Master’s degree in an appropriate subject. In exceptional cases, we may consider equivalent professional experience and/or qualifications. English language proficiency is required at a minimum of IELTS band 6.5 with no component score below 6.0.

Specific candidate requirements
We are looking for a talented student with a strong background in Molecular and Cellular Biology. Experience or an interest in bioinformatics techniques will be an advantage.

How to Apply
We’d encourage you to contact Dr Rhiannon McGeehan () 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 PHBM47021020 when applying.

Funding Notes

The bursary is available to UK and EU students only and covers tuition fees and an annual maintenance grant of £15,009 (UKRI 2019/20 rate) for three years. Bursary recipients will also receive up to £1,500 per year for research project costs, as well as office space and computing facilities.

References

(1)Lloyd RE, et al. (2015). Identification and functional prediction of mitochondrial complex III and IV mutations associated with glioblastoma. NeuroOncol. 17(7):942-52. (2)Keatley K, et al. (2019). Integrated Approach Reveals Role of Mitochondrial Germ-Line Mutation F18L in Respiratory Chain, Oxidative Alterations, Drug Sensitivity, and Patient Prognosis in Glioblastoma. IntJMolSci. 9;20(13).

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