Parkinson's disease unit, Neurogenetics Research Laboratory

Lab head: Dr Jin Sung Park
Location: Level 11, Kolling Institute of Medical Research (Northern Clinical School)

Among the causative genes of familial Parkinson’s disease (PD), Mutations in Parkin are thought to cause PD by impairing the removal of dysfunctional mitochondria (mitophagy). After the recent discovery that induction of an alternative mitophagy can improve mitochondrial function in Parkin-related PD, we are currently working to improve its efficiency by manipulating several molecules involved in this pathway. For this, we are keen to recruit an enthusiastic honours student who will be involved in one of the projects and contribute to the development of a highly effective treatment in PD by improving mitochondrial function.

Lab members: 1 Senior Research Fellow, 2 Postdoctoral scientists
Funding: Parkinson's NSW and internal funds
Research approach equipment: We investigate various aspects of mitochondrial function in conventional and patient-derived cell models such as fibroblasts and iPS cells using a broad range of molecular biology techniques including lentivirus system and gene expression analysis, immunocytochemistry, protein analysis and biochemical assays.

M. Sue, J.-S. Park and B. Koentjoro (2015), Compositions and methods for the treatment or prevention of neurodegenerative disorders. International (PCT) Patent application (P093792C) (pending)

B. Koentjoro, J.-S. Park, A.D. Ha and C.M. Sue (2012), Phenotypic Variability of parkin mutations in Single Kindred, Mov. Disord., 27(10):1299-1303

Development of highly effective treatment on mitochondrial dysfunction in Parkinson's disease

Primary supervisor: Jin Sung Park

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder. Patients with PD have a specific loss of dopaminergic neurons in the substantia nigra. The cause of this neurodegeneration is still unknown, but both genetic and environmental factors are known to play key roles. Mutations in Parkin are the most frequent genetic cause of autosomal recessive early-onset PD. The Parkin gene encodes an E3 ubiquitin ligase which mediates protein degradation through the ubiquitin-proteasomal system. Recently, there has been a link between PD and mitophagy, a removal of mitochondria by autophagic degradation, through the PINK1/Parkin pathway. Parkin mutations are strongly associated with impaired mitophagy and mitochondrial dysfunction in cellular models of PD. Previously, we identified the first case of a homozygous Parkin mutation carrier who had no Parkin protein, but did not develop PD. In further investigation, we discovered that a Parkin-independent mitophagic pathway compensated for the loss of Parkin in the asymptomatic carrier, suggesting its therapeutic potential for PD-associated mitochondrial dysfunction by restoring mitophagy. Meanwhile, several proteins have been shown to be involved in the pathway, but their roles in mediating mitophagy remain unclear.

In this project, we will investigate the role of several proteins associated with the Parkin-independent mitophagic pathway in modulating the efficiency of the pathway in cell lines derived from Parkin/PINK1-related PD patients using various techniques including cell culture, gene expression analysis using quantitative real-time RT-PCR, manipulation of gene expression by siRNA and lentivirus, Western blotting, immunocytochemistry, confocal microscope-assisted live cell imaging and biochemical assays.

Discipline: Pathology
Co-supervisors: Carolyn Sue, Brianada Koentjoro
Keywords: Parkinson's disease, Cell & Molecular Biology, Bioenergetics