Autophagy and mitochondrial quality control in disease Lab Head Profile Michael's research interests are focused on autophagy pathways and various aspects of mitochondrial biology in health and disease.
Michael was awarded his PhD from La Trobe University studying the assembly of membrane protein complexes in mitochondria and their defects in energy generation disorders. In 2010, as an NIH fellow, Michael conducted his post doctoral research studies with Richard Youle (National Institutes of Health, Bethesda, USA) working on mitochondrial dysfunction in Parkinson's disease. His post doctoral work focused on the Parkinson's disease proteins PINK1 and Parkin and their role in maintaining mitochondrial health through a degradative process termed mitophagy. The work led to Michael receiving the 2013 ASBMB Boomerang Award and in 2014 he returned to Australia to join the Department of Biochemistry and Molecular Biology at Monash University. Autophagy provides nutrients during starvation, maintains cellular quality control, helps cells defend against invading pathogens and is involved in cell death pathways. An autophagosome containing a mitochondrion imaged by transmission electron microscopy. During autophagy, cytosolic components are engulfed by a double membrane structure called an autophagosome. Autophagosomal contents are subsequently degraded following fusion of the autophagosome with a lysosome. Autophagy can be activated in response to starvation where recycling of degradation products provides both energy and building blocks for essential cellular processes. Starvation induced autophagy is largely a non selective process that randomly packages cellular material into autophagosomes. Selective forms of autophagy are activated in response to specific cellular stresses such as clearance of dysfunctional mitochondria through mitophagy, and removal of invading bacteria through xenophagy. Failure of either starvation induced autophagy, mitophagy or xenophagy can perturb cellular functions and cause cell death. It is therefore essential to understand how autophagosomes form during both selective and non selective autophagy. Using high resolution imaging, cell biology techniques and 3D structural analyses of autophagosomes, we aim to decipher how autophagosomes are built during cellular stress as well as characterise the factors that drive autophagosome formation. Damaged mitochondria (red) oakley black iridium being engulfed by an autophagosome (green) during PINK1/Parkin mitophagy. PINK1/Parkin mitophagy and Mitochondrial quality control in Parkinson's disease Parkinson's disease (PD) is one of the most common of the neurodegenerative disorders, affecting 1 2% of the population worldwide. Multiple lines of evidence place mitochondrial dysfunction as a central player in the pathogenesis oackley sunglasses of sporadic PD, and studies of genes associated with familial PD demonstrate convergent pathways involving oxidative stress and mitochondrial dysfunction. Two proteins commonly mutated in familial PD, PINK1 and Parkin, play a key role in maintaining mitochondrial integrity by identifying damaged mitochondria and degrading them through a selective form of autophagy termed mitophagy. PINK1 functions as a molecular sensor oakley usa of mitochondrial health by specifically accumulating on the outer membrane of damaged mitochondria. PINK1 mens oakley glasses alerts Parkin to damage by recruiting it to the dysfunctional mitochondrion and activating Parkin's ubiquitin ligase activity. Parkin then adds ubiquitin chains onto substrates on the outer mitochondrial membrane.
PINK1 phosphorylates these ubiquitin chains enabling them to act as molecular signals that recruit the machinery required to build autophagosomes. Basic model of PINK1/Parkin mitophagy Members of the lab Dr Thanh Nguyen (post doc) Dr Benjamin Padman (post doc) Joanne Usher (research assistant) Honours and PhD opportunitiesCandidates must have achieved a high level (H1) honours degree (or equivalent) in Biochemistry, Molecular Biology or Cell Biology (or a related discipline). Students currently undertaking an honours degree are also encouraged to apply.
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