Faculty of Medical and Human Sciences

High throughput screening of patient specific tumour cells: Towards personalised treatment in recurrent glioblastoma multiforme

Dr Brian Bigger, Dr Ian Kamaly-Asl, Dr Martin McCabe, Dr Catherine McBain

The aim of this fully-funded 3-year PhD project is to assess the potential of personalised glioblastoma multiforme (GBM) treatment in combination with High Throughput Compound Screening (HTCS). Patient-specific GBM cancer stem cells (CSCs) will provide the basis of a feasibility trial to individualise chemotherapy in patients with recurrent GBM.

Improving the outcome of patients with GBM is challenging. Disease recurrence in these patients is typical and overall survival at 3 years is lower than 5%.  Despite this, management of recurrent disease is unclear and treatment decisions often empirical. Personalized treatment would be attractive, but is currently hampered by the heterogeneity of cell populations in each tumour as well as inter-tumoural heterogeneity.

CSCs have been documented in several types of cancer including GBM. This subpopulation can recapitulate human tumours in xenografts as well as differentiate into cells of neuronal, astrocytic lineages. CSCs have also been shown to be resistant to radiation and chemotherapeutics and are thought to be responsible for disease recurrence. They represent a potential target for therapeutics in GBM.

HTCS combined with algorithmic image analysis is a powerful method extensively used by the pharmaceutical industry as a drug discovery tool. Few studies have applied this technology to patient specific CSCs.

Our hypothesis is that standard treatment regimen alters the chemosensitivity profile of the cell line. We also expect to see higher resistance to drug sensitivity in 3D cultures, i.e. cell lines derived at re-resection show increased resistance to chemotherapy agents.

The project represents a 3-year feasibility study to introduce HTCS into the treatment of GBM with significant clinical potential.

Extensive training will be provided in lab/clinical techniques such as primary cell culture, orthotopic models of primary brain tumours, stem cell culture and expansion techniques, in vivo imaging, RNA sequencing.

Successful completion of this PhD would provide an ideal platform for progression into a variety of career positions within academic or industrial settings involving biotechnology, regenerative medicine, neuroscience, oncology or medical imaging.

This 3-year full-time Christie Charitable Fund supported studentship provides full coverage of UK/EU tuition fees and an annual minimum tax-free stipend at RCUK rates (currently £13, 863p.a.) The project is due to commence between April-September 2015 subject to the preference of the successful candidate and is open to UK/EU nationals only due to the nature of the funding.  Preference is for an April start if possible.

Applicants should hold (or expect to obtain) a minimum upper-second honours degree (or equivalent) in cell biology, biochemistry, neuroscience, materials science, medical imaging, or a related biological/medical science area. Previous experience of some of the techniques referenced above would be an advantage, as would a related Masters qualification.

Please direct applications in the following format to Dr Brian Bigger (brian.bigger<στο>manchester.ac.uk):

• Academic CV
• Official academic transcripts
• Contact details for two suitable referees
• A personal statement (750 words maximum) outlining your suitability for the study, what you hope to achieve from the PhD and research experience to date.

Any enquiries relating to the project and/or suitability should be directed to Dr Bigger. Deadline for applications: Friday 12 December 2014.

http://www.human-development.manchester.ac.uk/staff/BrianBigger

http://www.human-development.manchester.ac.uk/

http://www.population-health.manchester.ac.uk/imaging/

http://www.mhs.manchester.ac.uk/postgraduate/