title: Using Caenorhabditis elegans as a model system to study protein homeostasis in a multicellular organism.
abstract: The folding and assembly of proteins is essential for protein function, the long-term health of the cell, and longevity of the organism. Historically, the function and regulation of protein folding was studied in vitro, in isolated tissue culture cells and in unicellular organisms. Recent studies have uncovered links between protein homeostasis (proteostasis), metabolism, development, aging, and temperature-sensing. These findings have led to the development of new tools for monitoring protein folding in the model metazoan organism Caenorhabditis elegans. In our laboratory, we combine behavioral assays, imaging and biochemical approaches using temperature-sensitive or naturally occurring metastable proteins as sensors of the folding environment to monitor protein misfolding. Behavioral assays that are associated with the misfolding of a specific protein provide a simple and powerful readout for protein folding, allowing for the fast screening of genes and conditions that modulate folding. Likewise, such misfolding can be associated with protein mislocalization in the cell. Monitoring protein localization can, therefore, highlight changes in cellular folding capacity occurring in different tissues, at various stages of development and in the face of changing conditions. Finally, using biochemical tools ex vivo, we can directly monitor protein stability and conformation. Thus, by combining behavioral assays, imaging and biochemical techniques, we are able to monitor protein misfolding at the resolution of the organism, the cell, and the protein, respectively.
authors.affiliation: Department of Life Sciences, National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev.
authors.forename: Ido
authors.initials: I
authors.lastname: Karady
authors.forename: Anna
authors.initials: A
authors.lastname: Frumkin
authors.forename: Shiran
authors.initials: S
authors.lastname: Dror
authors.forename: Netta
authors.initials: N
authors.lastname: Shemesh
authors.forename: Nadav
authors.initials: N
authors.lastname: Shai
authors.forename: Anat
authors.initials: A
authors.lastname: Ben-Zvi
mesh_terms: D000367:Age Factors; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D006706:Homeostasis; D023421:Models, Animal; D011487:Protein Conformation; D017510:Protein Folding; D055550:Protein Stability; D013312:Stress, Physiological / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins