Investigation of the pathogenic effects of mutations in the polymerase gamma gene

PhD Top-up Scholarships

$90,000 AUD

01/02/2010 → 01/02/2014

Carolyn Sue


Paula Woodbridge


University of Sydney


Prof Carolyn Sue

Project Name

Investigation of the pathogenic effects of mutations in the polymerase gamma gene

Project Details

Mitochondrial dysfunction causes a range of early-onset neurological conditions and contributes to neurodegenerative conditions such as Parkinson Disease. The mechanisms of neuronal damage are unknown, and the study of these at a cellular level may lead to improved treatment and greater understanding of the role of both nuclear – and mitochondrial – DNA mutations in both rare and common conditions.

This project focuses on complex I deficiency, the most common mitochondrial respiratory chain defect. Using multiple primary and established cell culture models, it studies the effects of mutations on mitochondrial membrane potential, reactive oxygen species, ATP production, apoptosis and cellular calcium dynamics, primarily using techniques in fluorescent microscopy and cell biology, as well as biochemistry and molecular biology. We already have data on most of these parameters for patient fibroblast cell lines with characterised mutations in complex I subunits and assembly factors.

This project focuses on cell culture models that more closely reflect neuronal function to study possible mechanisms of neuronal damage. In particular, this includes primary neural cell cultures established from two mouse models with complex I deficiency resulting from mutations in two different nuclear encoded complex I subunits. We access two other models, namely olfactory stem cell cultures derived from patients with mtDNA mutations (from Prof Carolyn Sue) and mouse embryonic stem cells with mitochondrial DNA mutations (from Prof Doug Turnbull).