Steven Zuryn

With life expectancies increasing around the world, neurodegenerative disorders (e.g. Alzheimer's disease -AD, Parkinson's disease - PD, Motor neuron diseases - MND) represent an enormous disease burden on individuals, families, and society. Two forms of cellular stress are a hallmark of age-related neurodegenerative disease: mitochondrial dysfunction, and toxicity resulting from conformationally challenged, aggregate-prone proteins. Although direct links between these factors and human disease are sometimes elusive, it is clear that such stressors ultimately lead to a decline in individual neuron function over time.

The Zuryn lab uses cutting-edge molecular and cellular techniques in C. elegans and human cell culture systems to understand the fundamental mechanisms by which cells respond to and mitigate mitochondrial dysfunction. Mitochondria harbour their own genome (mtDNA), which is prone to accumulating mutations as we age leading to dysfunction that may contribute to the progressive nature of neurodegenerative diseases. The Zuryn lab have recently discovered that certain cell types in the body are prone to propagating mtDNA mutations more than others (Ahier et al. Nature Cell Biology 2018) and that aggregate-prone disease-associated proteins can enhance the accumulation of mtDNA mutations in neurons by inhibiting quality control pathways, such as mitophagy (Cummins et al. EMBO Journal 2019, Ahier et al Cell Reports 2021).

Excitingly, the Zuryn lab are now uncovering multiple distinct mechanisms that counteract the mtDNA mutations themselves by developing novel genetic tools that allow them to probe cellular responses and protective mechanisms that reverse the effects of mtDNA damage (Dai et al. Nature Cell Biology 2023).

Furthermore, they have revealed an ancient epigenetic mark (6mA) that decorates the mtDNA and protects against the inheritance of mtDNA mutations to future generations (Hahn et al. Cell Metabolism 2024).

The overarching aim of the Zuryn lab is to discover new molecules and mechanisms that protect cells from the effects of mitochondrial dysfunction and that may be used as novel therapeutics to counteract mitochondrial and neurodegenerative disease.