China Scholarship Council: Mapping mitochondrial signalling pathways in neurodegeneration

Our laboratory has dissected the function of two Parkinson’s disease-linked genes encoding the protein kinase, PINK1 and ubiquitin E3 ligase, Parkin, that has illuminated a highly conserved mitochondrial quality control pathway found in nearly every cell type including brain cells. Mitochondrial damage-induced activation of PINK1 stimulates phosphorylation-dependent activation of Parkin and ubiquitin-dependent elimination of mitochondria by autophagy (mitophagy).

In ongoing studies, we are investigating the key regulators of PINK1 and Parkin function using state-of-the-art mass spectrometry technologies combined with Cas9/CRISPR technologies to genetically knockout genes in somatic cell lines. We are also investigating the molecular mechanism of how PINK1 is activated. We have recently generated highly sensitive PINK1 monoclonal antibodies and wish to utilize these together with mass spectrometry methodologies to determine physiological binding partners of endogenous PINK1. Our lab also studies signalling in PD relevant cells including primary neuron cultures. 

The overall aim of the project is to uncover new mechanisms for how PINK1 activation induces mitophagy and the student will be trained in a variety of biochemical, CRISPR, and mass spectrometry methods towards addressing this question.