Mitochondrial Biomarkers and Drug Development for Personalised Treatment of Brain Cancer
Self-funded PhD students only
School of Pharmacy and Biomedical Sciences
Applications accepted all year round
Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults, and carries a dismal prognosis. Treatment is hampered by its unique biology, which means that each individual case can respond differently to existing therapies.
Due to current treatments that target nuclear DNA being so ineffective, researchers are turning to alternative targets within the cell, such as the mitochondria.
The goal of this PhD Project is to further develop this method of mitochondrial targeting when screening and treating brain cancer, to improve the currently dire mortality rate for this diagnosis.
The work on this project is split into 3 different research arms:
- Drug-sensitivity biomarker validation: in vitro using a large (20+) panel of GBM-biopsy derived cell lines (BTRC, UoP) and in vivo using a pre-clinical mouse model (Faculty of Medicine, Hammersmith Campus, Imperial College, London)
- Drug design and synthesis: of ~100 novel small molecule inhibitors designed specifically to target the mutant mitochondrial enzyme found in GBM-patients (Duquesne University, USA)
- Drug screening: high throughput screening of the inhibitors will be performed using our yeast model that has been genetically modified to contain the GBM-mutant mitochondrial enzyme (CNRS, France); the most promising candidates will then be tested in vitro on the panel of GBM cell lines mentioned above (BTRC, UoP)
Mitochondria are the energy-producing compartments inside cells, and mitochondrial alterations are a known hallmark of cancers. Mitochondria also have their own DNA (mtDNA).
Although numerous mutations have been found in brain tumour mtDNAs [LloydNeuroOnc15; LloydIJMS16, submitted], their potential for developing new and better treatments for GBM patients has not been fully explored.
We recently discovered an inherited mtDNA mutation that is more common in GBM-patients compared to healthy subjects. This mutation occurs in an important inhibitor binding site within a mitochondrial enzyme that plays a key role in cellular energy production [LloydNeuroOnc15].
Significantly, the mutation seems to influence mitochondrial-targeted drug sensitivity (SongHumMut16; KeatleyPhDthesis16; KeatleyHumMut16, in prep). Preliminary data also suggests that a further four mitochondrial factors also influence mitochondrial-targeted drug sensitivity.The long-term goal of this project is to provide clinicians with a simple genetic test they can use to decide which treatment will be most effective for each patient. If just one of the biomarkers or drugs under development here is even partially successful, it has the potential to transform the current chance of survival for GBM patients.
This project is a collaboration between our Brain Tumour Research-funded research centre and three other high impact research centres based in the UK, France and US.
PhD full-time and part-time courses are eligible for the Government Doctoral Loan.
- Home/EU/CI full-time students: £4,327 p/a*
- Home/EU/CI part-time students: £2,164 p/a*
- International full-time students: £15,900 p/a*
- International part-time students: £7,950 p/a*
Bench fees may also apply - for more information please contact the project supervisor.
By Publication Fees 2019/2020
- Members of staff: £1,610 p/a*
- External candidates: £4,327 p/a*
*All fees are subject to annual increase.
- A good honours degree or equivalent in a relevant subject or a master’s degree in an appropriate subject.
- Exceptionally, equivalent professional experience and/or qualifications will be considered.
- All applicants are subject to interview.
- English language proficiency at a minimum of IELTS band 6.5 with no component score below 6.0.
Make an Enquiry
How to apply
To start your application, or enquire further about the process involved, please contact Informal enquiries are welcome and can be made to Dr Rhiannon McGeehan (email@example.com) and Dr Katerina Lalatsa (firstname.lastname@example.org), quoting both the project code PHBM3070217 and the project title.
You can also visit our How to Apply pages to get a better understanding of how the PhD application process works.