The Ganley lab is interested in unravelling the molecular mechanism of autophagy (which literally translates from the Greek meaning to eat oneself). Autophagy is a critical lysosomal degradation pathway that functions to clear the cell of potentially damaging agents, such as protein aggregates or faulty mitochondria. Importantly, autophagy appears to be dysregulated in many diseases and therefore its modulation could lead to novel therapies. However, to enable this, we first need to understand the machinery involved.

A project is available to decipher the signals that lead to the specific autophagy of mitochondria (termed mitophagy), a process that has strong links to cancer and in particular Parkinson’s disease. Following up on recently published work, the project will utilise state-of-the-art microscopy, cell biology, protein biochemistry and mass spectrometry to identify phosphorylation and ubiquitylation events involved in capturing mitochondria for degradation. As well as gaining experience in a wide variety of techniques, you will be part of a dynamic and collaborative team intent on making new scientific discoveries and producing the next generation of world-class scientists.

References

1. Ganley IG, Simonsen A. Diversity of mitophagy pathways at a glance. J Cell Sci. 2022 Dec 1;135(23):jcs259748. PMID: 36504076.
2. McWilliams TG, Prescott AR, Montava-Garriga L, Ball G, Singh F, Barini E, Muqit MMK, Brooks SP, Ganley IG. Basal Mitophagy Occurs Independently of PINK1 in Mouse Tissues of High Metabolic Demand. Cell Metab. 2018 Feb 6;27(2):439-449. PMID: 29337137.
3. Wilhelm LP, Zapata-Muñoz J, Villarejo-Zori B, Pellegrin S, Freire CM, Toye AM, Boya P, Ganley IG. BNIP3L/NIX regulates both mitophagy and pexophagy. EMBO J. 2022 Dec 15;41(24):e111115. PMID: 36215693.
4. Singh F, Prescott AR, Rosewell P, Ball G, Reith AD, Ganley IG. Pharmacological rescue of impaired mitophagy in Parkinson's disease-related LRRK2 G2019S knock-in mice. Elife. 2021 Aug 3;10:e67604. PMID: 34340748.