Applications are invited from outstanding candidates to join a Cancer Research UK funded PhD programme at the Cancer Research UK Edinburgh Centre, part of the MRC Institute of Genetics and Molecular Medicine (IGMM) at the University of Edinburgh.
Glioblastoma (GBM) is the most common type of malignant brain tumour among adults. The discovery of new effective treatments for GBM has been limited by a lack of relevant laboratory models which accurately recapitulate disease pathophysiology and mimic the multiple redundant and adaptive signalling mechanisms that lead to rapid drug resistance in patients.
This project will apply the latest advances in high resolution in vitro and in vivo imaging technologies to develop more relevant and informative 3-dimensional (3D) in vitro and in vivo GBM models for drug discovery. Multiparametric high content imaging at single cell resolution will be integrated with mass spectrometry and antibody-based proteomics (reverse phase protein array and micro-western) to understand drug mechanism-of-action and mechanisms of intrinsic and adaptive drug resistance. Resistance pathways will be mapped to drug target databases to build novel drug combination hypotheses for subsequent validation across novel in vitro 2D and 3D models incorporating patient derived glioma stem cells and cellular components of the natural blood-brain-barrier (BBB). Each drug combination will be tested as a dose-ratio matrix to calculate synergistic, additive and antagonistic effects. The most promising drug combinations will subsequently be packaged into BBB penetrating nanoparticles for preclinical testing across the suite of new in vitro and in vivo GBM models using state-of-the-art imaging to quantify drug combination delivery and therapeutic response.
The University of Edinburgh, University of Oxford, Massachusetts Institute of Technology and a number of pharmaceutical industry partners have joined forces to use our combined expertise to develop an innovative drug combination discovery and delivery platform specifically tailored for GBM. The PhD project described above will feed directly into this wider global initiative.