MRC DiMeN Doctoral Training Partnership: Mitochondrial quality control for a healthy brain

Description

A deterioration in mitochondrial health is linked to normal ageing and several neurodegenerative conditions, including Parkinson’s (PD), Alzheimer’s and Motor Neuron Diseases. We are particularly interested in PD for which there is good evidence that a defect in the clearance of damaged mitochondria by a process called mitophagy can lead to the condition. At the core of this pathway are two proteins (PINK1 and Parkin) which have been genetically linked to PD, through loss of function mutations. A major challenge in the field is how to activate this pathway or compensate for its loss. One approach we have been working on together with industrial partners is to inhibit a deubiquitylase enzyme called USP30. This has led to some promising pre-clinical results which have provided the green light for clinical trials to begin this year. With this project we are now seeking to build out knowledge of the pathway, by studying two other less well studied proteins, which may offer new therapeutic strategies. The host laboratory is a vibrant and well equipped biochemistry and cell biology environment (http://pcwww.liv.ac.uk/~clague/). We use tissue culture models that include neurons induced from iPSC cells. Our primary aims are to gain fundamental mechanistic insights leading to high quality publications and to enable the PD drug discovery pipeline.

Benefits of being in the DiMeN DTP:

This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle, York and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of-the-art facilities to deliver high impact research.

We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.

Being funded by the MRC means you can access additional funding for research placements, training opportunities or internships in science policy, science communication and beyond. Further information on the programme and how to apply can be found on our website:

https://www.dimen.org.uk/