Damage control: exploring the mechanisms of mitophagy in neurons and organoids

Project type

  • PhD
  • Masters by Coursework
  • Honours

Project details

Mitophagy is an important cellular pathway that keeps mitochondria healthy by selectively degrading those that become damaged. Mitophagy dysfunction is linked to neurodegenerative diseases including Parkinson’s disease, and therefore the goal of this project is to understand how mitophagy works in neurons.Students will utilise stem cell derived neurons and midbrain organoids differentiated from healthy controls, Parkinson’s disease patients, or gene edited lines deficient in mitophagy, to uncover the key mechanisms of neuronal mitophagy and how it can go wrong in disease.

Students will develop fundamental skills in cell culture, viral transductions, genome engineering (CRISPR/Cas9), and molecular biology. In addition, students will learn how to visualise mitophagy in cells and organoids by advanced imaging techniques. Students will therefore gain experience in a range of scientific approaches, providing them with a strong scientific foundation to build their research career.

Scientific diagram by Michael Lazarou
A midbrain organoid used for mitophagy analyses including imaging. Organoids are generated in collaboration with researchers at the Florey Institute and University of Sydney (Lachlan Thompson and Clare Parish)

About our research group

The Lazarou lab is focused on understanding pathways that keep our mitochondria fit and healthy. This is important because failure to maintain mitochondrial health results in a range of human diseases including neurodegeneration.

Our lab has a particular interest in Parkinson’s disease, the world’s second most common neurodegenerative disorder, which affects 1-2% of people.

Two proteins commonly mutated in familial Parkinson’s disease, PINK1 and Parkin, play a key role in maintaining mitochondrial health by identifying damaged mitochondria and degrading them through mitophagy. Placed within the Parkinson’s Disease Research Centre at WEHI, our lab investigates the molecular mechanisms and cell biology of PINK1/Parkin mitophagy and other mitophagy pathways, with the goal of translating our discoveries to boost or stimulate mitophagy to overcome disease from Parkinson’s disease and beyond.

Education pathways