Alban Ordureau, a former student and postdoc in Philip Cohen's lab in the MRC-PPU (2007-2012) has been awarded a prestigious Lefler Fellowship to continue his research at Harvard medical School, Boston, USA, which is aimed at clarifying the molecular mechanisms underlying Parkinson's disease.
The Lefler Fellowship was established by the Department of Neurobiology at Harvard Medical School to provide support for the training of the most promising pre-doctoral students and postdoctoral fellows working on projects relevant to neurodegeneration and neurodevelopment.
Over the past two and half years, while working and as a post-doctoral fellow in the laboratory of Wade Harper at Harvard Medical School, Alban has used state-of-the-art mass spectrometry and biochemistry techniques to uncover a feed-forward mechanism that regulates the activation of the E3 Ubiquitin Ligase Parkin by the protein kinase PINK1. This pathway, which is triggered by mitochondrial damage, is defective in Parkinson's disease. His studies, together that of other laboratories, including those of Miratul Muqit and Helen Walden in the MRC-PPU at Dundee, has shed new light on how the Parkin E3 ubiquitin ligase is activated by PINK1 and how the phosphorylation of ubiquitin chains retains Parkin on damaged mitochondria, allowing it to catalyse the ubiquitylation of mitochondrial outer membrane proteins to promote the removal of damaged mitochondria via mitophagy.
So far, our understanding of the PINK1-Parkin pathway has been based on studies with immortalized tissue culture cells engineered to express the normal and mutant forms of Parkin. There has been little attempt thus far to examine this biochemical pathway in a quantitative manner in primary neurons. With support from the Lefler Fellowship, Alban will pursue his quantitative analysis of the PINK1-Parkin pathway to systematically explore Parkin's activation mechanisms and the role of ubiquitin phosphorylation in neuronal mitophagy.
The Lefler Fellowship was established by the Department of Neurobiology at Harvard Medical School to provide support for the training of the most promising pre-doctoral students and postdoctoral fellows working on projects relevant to neurodegeneration and neurodevelopment.
Over the past two and half years, while working and as a post-doctoral fellow in the laboratory of Wade Harper at Harvard Medical School, Alban has used state-of-the-art mass spectrometry and biochemistry techniques to uncover a feed-forward mechanism that regulates the activation of the E3 Ubiquitin Ligase Parkin by the protein kinase PINK1. This pathway, which is triggered by mitochondrial damage, is defective in Parkinson's disease. His studies, together that of other laboratories, including those of Miratul Muqit and Helen Walden in the MRC-PPU at Dundee, has shed new light on how the Parkin E3 ubiquitin ligase is activated by PINK1 and how the phosphorylation of ubiquitin chains retains Parkin on damaged mitochondria, allowing it to catalyse the ubiquitylation of mitochondrial outer membrane proteins to promote the removal of damaged mitochondria via mitophagy.
So far, our understanding of the PINK1-Parkin pathway has been based on studies with immortalized tissue culture cells engineered to express the normal and mutant forms of Parkin. There has been little attempt thus far to examine this biochemical pathway in a quantitative manner in primary neurons. With support from the Lefler Fellowship, Alban will pursue his quantitative analysis of the PINK1-Parkin pathway to systematically explore Parkin's activation mechanisms and the role of ubiquitin phosphorylation in neuronal mitophagy.