Understanding the function of the E3 ligase Parkin in Parkinson’s disease

Understanding the function of the E3 ligase Parkin in Parkinson’s disease

Project details

Parkinson’s disease (PD) is caused by the excessive and progressive death of dopaminergic neruons that control motor function. What causes the death of these neurons remains unclear.

Parkin is an E3 ubiquitin ligase that is a critical effector of mitophagy (mitochondrial quality control). Its function is important to prevent early onset PD with 50 per cent of early onset PD cases caused by mutations in Parkin. Our studies have revealed a novel intersection between the machinery that controls mitophagy and that which controls apoptotic cell death.

This project will utilise multi-disciplinary approaches to interrogate how Parkin mediates mitophagy and determines cell survival. This insight will inform how we might better target the process to treat disease and whether Parkin itself might be a new drug target. The project will involve diverse approaches including cell culture, microscopy, protein chemistry and mass spectrometry.

References:

Bernardini et al, Oncogene 2016 36(10):1315
Bernardini et al, EMBO J 2019 38(2)
Gladkova et al, Nature 2018 559(7714):410-414

About our research group

The lab currently comprises three PhD students, and a post-doctoral research assistant. Each of the lab members have their own research focus within the broader context of understanding the fundamental processes of apoptosis and mitochondrial quality control (mitophagy). The lab collaborates widely within the Institute and also with external labs. A key collaborator in our research into Parkin and Parkinson’s disease is Professor David Komander (Head, Ubiquitin Signalling division). Research positions are available for students with a passion for biological research and an interest in neurodegeneration and cancer.

 

 

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