Ph.D.: The Hebrew University of Jerusalem, Israel
Post-doctorate: Northwestern University, Evanston, USA
Position: Senior Lecturer
Department of Life Sciences
Faculty of Natural Sciences
E-mail: anatbz@bgu.ac.il
Webpage: http://in.bgu.ac.il/en/natural_science/LifeSciences/Pages/staff/Anat_Ben-Zvi.aspx
Protein folding homeostasis in a multicellular organism
The long-term health of all metazoan cells is linked to protein quality control. All cells have highly conserved pathways that detect, prevent, and resolve protein damage. The absence or malfunction of these pathways can result in developmental arrest, functional decline of diverse cellular machinery, and the onset of protein misfolding diseases. When protein folding and clearance balance protein biosynthetic processes, protein-folding homeostasis (proteostasis) is achieved, preventing the accumulation of misfolded protein and aggregates within cells.
Most protein misfolding diseases exhibit tissue-selective impairment. However, the mechanism for this selectivity and vulnerability is not known. Given that cell-type-specific and tissue-specific regulation of protein expression results in different cellular functions and morphological characteristics, protein-folding requirements and therefore its regulation may also vary between tissues. We aim to elucidate how cell-specific differences in protein expression affect cellular quality control networks. Caenorhabditis elegans provides an opportunity to study the complex biological networks that determine proteostasis in an intact organism. To understand how cell-specific differences in protein expression affect cellular quality control networks we apply C. elegans model system to study protein folding in the cell, via a combination of cell biological, biochemical, and genetic approaches to:
1. Develop a toolbox of folding sensors to monitor proteostasis challenges and their determine the genetic and physical interactions with the cellular folding machinery.
2. Identify cell-specific and cell-nonspecific modifiers of proteostasis in C. elegans and compare the folding capacity of different cell types.
3. Evaluate the impact of the expression of various aggregation-prone proteins on the folding capacity of different cell types. Examine and compare proteostasis networks in different cell types.
Gidalevitz T*., Ben-Zvi A*., Ho K.H., Brignull H.R. and Morimoto R.I (2006). Progressive Disruption of Cellular Protein Folding in Models of Polyglutamine Diseases. Science 311(5766):1471-1474.
Ben-Zvi A., Miller E.A and Morimoto R.I (2009). Collapse of Proteostasis Represents an Early Molecular Event in C. elegans Aging. Proc. Natl. Acad. Sci. USA 106(35):14914-14919.
Bar-Lavan Y., Kosolapov L., Frumkin F. and Ben-Zvi A. (2011). Regulation of cellular protein quality control networks in a multi-cellular organism. FEBS J. 279(4):526-531.
Shemesh N., Shai N. and Ben-Zvi A. (2013). Germline stem cell arrest inhibits the collapse of somatic proteostasis Early in Caenorhabditis elegans Adulthood. Aging Cell 12(5):814-822.
Feldman N., Kosolapov L. and Ben-Zvi A. (2013). Fluorodeoxyuridine improves Caenorhabditis elegans proteostasis independent of reproduction onset. PLOS ONE 9(1):e85964.
Karady I., Frumkin A., Dror S., Shemesh N., Shai N. and Ben-Zvi A. (2013). Using Caenorhabditis elegans as a model system to study protein homeostasis in a multicellular organism. J.Vis.Exp (82):e50840. doi: 10.3791/50840.
