Mutations of mitochondrial DNA (mtDNA) cause a wide range of diseases that cause severe disability and shorted lifespan and represent a major challenge in modern medicine. Unfortunately, treatment remains restricted to symptomatic control, and no significant disease modifying treatments are available.
Nanna therapeutics have developed small molecule compounds and technologies to assay the effects of a novel libraries of small molecules on mitochondrial function using a unique high throughput micro-fluidic platform requiring minute samples. In the Duchen lab, we will generate iPS cells from patient derived fibroblasts carrying mtDNA mutations. These will be differentiated into skeletal muscle and neurons using established protocols already in use in the lab. We will establish the impact of the mtDNA mutation on cell biochemistry and physiology and working with Nanna therapeutics we will assay and screen for compounds to identify new potential therapeutic molecules.
For positive hits we will explore mechanism. We will use confocal fluorescence microscopy to measure mitochondrial morphology, membrane potential, glycolytic flux, redox state, calcium signalling and mitophagic flux and the ‘Seahorse’ to measure rates of oxygen consumption and lactic acid generation.
This is an exciting opportunity for a student to work in an excellent and well equipped academic laboratory and gain exposure to industrial research at the same time. Our hope is that we will elucidate the specific consequences of different mtDNA mutations for cell and mitochondrial function and identify potential novel therapeutics with translational potential for a group of diseases for which at present there are no effective treatments available.
Fully funded place including home (UK) tuition fees and a tax-free stipend in the region of £17,009. Students from the EU are welcome to submit an application for funding, any offers will be subject to MRC approval and criteria.