Background

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. 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 protein homeostasis (proteostasis) in an intact organism.

Current Projects

1. Develop a toolbox of folding sensors to monitor proteostasis challenges. 2. Determine the genetic and physical interactions of various metastable proteins and sensors with the cellular folding machinery. 3. Identify cell-specific and cell-nonspecific modifiers of proteostasis in C. elegans and compare the folding capacity of different cell types. 4. Evaluate the impact of the expression of various aggregation-prone proteins on the folding capacity of different cell types.

Recent Publications

Frumkin A., Dror S., Pokrzywa W., Bar-Lavan Y., Karady I., Hoppe T. and Ben-Zvi A. (2014) Challenging muscle homeostasis uncovers novel chaperone interactions in Caenorhabditis elegans. Front. Mol. Biosci. 1:21. doi: 10.3389/fmolb.2014.00021

Valenci I., Yonai L., Bar-Yaacov D., Mishmar D. and Ben-Zvi A. (2015) Parkin modulates heteroplasmy of truncated mtDNA in Caenorhabditis elegans. Mitochondrion 20: 64-70.

Amara N., Gregor R., Rayo J., Dandela R., Daniel E., Liubin N., Willems M., Ben-Zvi A., Krom B and MeijlerM.M. (2016) Fine-Tuning Covalent Inhibition of Bacterial Quorum Sensing. ChemBioChem, 17(9): 825-835.

Bar-Lavan Y., Shemesh N., Dror S., Ofir R., Yeger-Lotem E. and Ben-Zvi A. (2016) A differentiation transcription factor establishes muscle-specific proteostasis in Caenorhabditis elegans, PLoS Genet, 12(12):e1006531.

Smoly I.Y., Shemesh N., Ziv-Ukelson M., Ben-Zvi A. and Yeger-Lotem E. (2017) An asymmetrically balanced organization of kinases versus phosphatases across eukaryotes determines their distinct impacts. PLoS Comput Biol, 13(1):e1005221.

Ph.D. The Hebrew University of Jerusalem, 2004.