CRISPR-based mitophagy screens for regulators of mitochondrial protein import quality control

Mitophagy is a highly selective form of autophagy (cellular self-eating) for the removal of damaged or redundant mitochondria. Failures in its regulation are implicated in numerous human diseases. Our understanding of mitophagy in mammalian cells has advanced impressively, but we still lack essential understanding of its control during physiological mitochondrial stress. This project will bridge this knowledge gap by screening for individual proteins and associated pathways that coordinate the mitophagy response specifically during mitochondrial protein import arrest. Mitophagy reporter cell-lines will be adapted as platforms for CRISPRi (CRISPR interference) and/or CRISPRa (CRISPR activation)-based screening for regulators of mitophagy during mitochondrial protein import blockage. Mechanistic studies will then be carried out in whole cells and using isolated mitochondria to determine the roles of important individual proteins and their pathways. Multidisciplinary training will be provided in key areas, including: state-of-the-art widefield and confocal microscopy, with automated high content analysis; in vitro mitochondrial import assays; CRISPRi/a assay design; bioinformatics and large data set analytical methods; mechanistic cell biology.

Website: https://thelanelab.blogs.bristol.ac.uk

Twitter: @Jon_D_Lane 

Closing deadline: Monday 6 December, midnight.

Full details on the BBSRC SWBio DTP can be found at: https://www.swbio.ac.uk/programme/projects-available/

To apply, please use the following link: Start your application | Study at Bristol | University of Bristol. To choose the correct programme, please start to type 'Southwest' in the search box and the SWBio programme will appear.