Exploring a mitochondrial role for alpha-synuclein in Parkinson’s disease pathophysiology

• Honours
• PhD and Graduate Research Masters

Alpha-synuclein (aSyn) is a protein associated with Lewy bodies, the primary pathological feature of Parkinson’s disease (PD). Impaired mitochondrial health has emerged as a driver of PD and may be initiated or exacerbated by aSyn mutations and aggregation. Specifically, aSyn has been implicated in PINK-Parkin mitophagy, a process that clears damaged mitochondria in cells. Mutations in PINK1 and Parkin cause genetic forms of PD and are associated with elevated risk of sporadic PD.

This project will aim to leverage our expertise in mitochondrial biology to determine if and how mitochondria are impacted by aSyn in PD disease models. Students will generate induced and ex-vivo neuronal culture models, learn cell viability assays, and gain skills in microscopy, molecular biology, and mitochondrial biology.

The Dewson Lab’s research is focused on the powerhouses of cells, structures called mitochondria. Maintaining the integrity and function of mitochondria is essential for cells to survive and to grow. Mitochondria are also central to the process of cell death termed apoptosis.

Defective function and integrity of mitochondria can lead to many diseases including Parkinson’s disease and cancer. Our research uses innovative approaches to better understand how cells in our body maintain their mitochondria to promote cell survival. This information is informing the development of new ways to treat a broad range of diseases with a specific focus on Parkinson’s disease.

Highlighted references:

• Mitochondria in neurodegenerative disease (Bernardini 2018 EMBO J 2018 38(2), Gan 2022 Nature 602(7896):328, Schmidt CDD 2019 28(2):570, Masaldan Biochem Soc Trans. 2022 50(2):783).
• Control of apoptosis (Dewson Molecular Cell 2008 30(2):369, Dewson Molecular Cell 2009 36(4):696)