Numerous diseases are manifested by the accumulation and aggregation of intracellular proteins, including neurodegenerative polyglutamine (polyQ) expansion disorders such as Huntington’s disease. In most of these disorders, fragments of the disease-related protein initiate aggregation and toxicity. Our lab is interested in the clearance of these polyQ fragments. We have developed different tools to mimic and visualize polyQ fragment generation in cells, and want to identify cellular proteins involved in the clearance of polyQ aggregates and study their function. These proteins include proteases (like the proteasome) or peptidases that can target intracellular polyQ peptides in vivo. Furthermore, the role of autophagy in the clearance of polyQ aggregates will be investigated. Both autophagy of large aggregates and selective autophagy via chaperone-mediated autophagy will be examined. Enhanced activity of these proteins could provide a strategy to prevent accumulation of toxic polyQ peptides
We study the processes to improve the degradation of aggregation-prone proteins in living cells. We use advanced fluorescence microscopy (including confocal imaging, FRET and FLIM) and correlative electron microscopy, and varied biochemical assays to analyze different stages of aggregation.
This research project to improve polyQ clearance was recently awarded with a Vidi grant from the Dutch government. We are looking for a post-doctoral fellow who will investigate and manipulate the autophagic route to remove aggregation-prone peptide aggregates. This will include the examination of known autophagy components, but also of a yet poorly understood autophagy pathway that we recently discovered using peptidase-resistant peptides. You will join a research group with several PhD students and technicians, all dedicated to various aspects of visualizing and manipulating polyQ aggregation and their clearance.
A Ph.D degree in molecular biology, cell biology and/or biochemistry is required. Previous experience with autophagy is a plus. Ability to work independently is expected.
We offer a position for 4 years with competitive salary. Our group resides within a research department dedicated to cell biology at the Academic Medical Centre, Amsterdam, the Netherlands, and embedded within a network of local research groups on neurodegeneration at the University of Amsterdam and the Netherlands Institute for Neuroscience.
Informal enquiries can be made to e.a.reits@amc.uva.nl
Also check our website at: http://www.amc.uva.nl/index.cfm?pid=2472
