MicroRNA control of the metabolic response to hypoxia in malignancy

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The project will develop these initial approaches further, utilising more advanced 3D culture techniques, including spheroid and rotary cell culture. This will allow more in depth assessment of the microRNA response to varying micro-environmental conditions, including hypoxia. Laser microdissection will be used to evaluate specific tumour cell niches and assess heterogeneity of the response, both in 3D cell culture and in patient tumour specimens. Imunohistochemistry will be informed to validate results at a protein level, using already constructed in house tissue microarrays. Effects can also be analysed at a metabolic level by mass spectrometry.Functional analysis of targets will be undertaken by microRNA or gene knock in/down, with proliferation, migration and invasion assays already in use in the laboratory. Orthotopic brain tumour models are also available to allow in vivo analysis of any candidates at the late stages of the project. We will seek to repurpose any known inhibitors of the metabolic pathways interrogated to test as possible candidate agents for GBM therapy.