Using C. elegans to monitor proteostasis imbalances
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Dr. Carmen Nussbaum-Krammer is a project group leader at the Center for Molecular Biology of Heidelberg University (ZMBH)...
Northeastern Illinois University
Dr. Cindy Voisine is an Associate Professor of Biology at Northeastern Illinois University. She obtained her PhD in...
Protein homeostasis, or ‘proteostasis’, is fundamental to cellular and organismal health. Conserved cellular processes cooperate to maintain a properly folded proteome by influencing protein synthesis, folding and clearance. Cells respond to proteostasis imbalances by activating the Heat shock response, the unfolded protein response (UPR) and the oxidative stress response (OxR) to readjust the cellular proteome. Alterations in proteostasis have been linked to age-related neurodegenerative diseases and cancers. Based on the high level of conservation, model systems such as C. elegans have been instrumental in understanding the role of proteostais in human health and disease. C. elegans possess many characteristics that make it an ideal experimental model including its short lifecycle, transparent cuticle and ease of chemical and genetic manipulations.
This collection will provide methodological strategies to monitor proteostasis at the cellular and organismal level in C. elegans. Stressors, such as misfolded disease proteins, can be experimentally introduced into specific tissues types while cellular and organismal response to proteotoxicity are monitored over time. Proteotoxicity leads to cellular dysfunction that can be quantitatively measured by phenotypic changes. Furthermore, activation of protective pathways in response to proteotoxic stress can be observed using fluorescent reporters. Genetic modifications and chemical treatments can then be employed to determine their effectiveness in readjusting proteostasis. The outcome of this series will provide a toolkit for probing and monitoring proteostasis, evaluating quality control systems that maintain a folded proteome, and investigating the dysregulation of these systems that lead to disease.
1Babraham Institute, 2Gurdon Institute, University of Cambridge, 3Department of Genetics, University of Cambridge, 4Wellcome Trust Genome Campus, Wellcome Trust Sanger Institute, 5Laboratory of Virology and Infectious Disease, The Rockefeller University
1Leibniz Research Institute for Molecular Pharmacology im Forschungsverbund Berlin, 2NeuroCure Cluster of Excellence, Charité - Universitätsmedizin Berlin, 3Molecular Neuroscience Group, Department of Chemical Engineering and Biotechnology, University of Cambridge, 4Cell Biology, University of Bremen