Reut Shalgi, PhD
Assistant Professor of Biochemistry
PhD, 2009 - Weizmann Institute of Science, Israel
Translational regulation in proteostasis and disease
Protein homeostasis (proteostasis) is the balance of protein synthesis, folding, localization and degradation. Cells need to respond rapidly to changing environments and maintain protein homeostasis dynamically throughout life. In my lab we try to understand how different cellular networks work together to maintain protein homeostasis. We focus on two crucial systems, thus far largely considered separate: (1) protein synthesis - primarily the ribosome; and (2) protein folding, which involves molecular chaperones. We discovered that chaperones, which sense perturbations in proteostasis, communicate this information to the translational machinery to tune protein synthesis in response to environmental cues. We use high throughput technologies, together with molecular and computational biology, to explore dynamic chaperone networks and their crosstalk with the translation machinery. We are interested in how chaperones control translation, and how translation is deregulated in neurodegenerative diseases such as Parkinson’s, Huntington’s, and ALS. For more information, see: http://reuts4.wix.com/reutshalgi
Shalgi R, Hurt JA, Lindquist S, and Burge CB 2014. Widespread inhibition of post-transcriptional splicing shapes the cellular transcriptome following heat shock. Cell Reports 7, 1362-1370. Featured in Nat Rev Mol Cell Biol
Shalgi R, Hurt JA, Krykbaeva I, Taipale M, Lindquist S, and Burge CB. 2013. Widespread regulation of translation by elongation pausing in heat shock. Molecular Cell 49, 439-452. Featured in Nature SMB and Nat Rev Genet
Dahary D*, Shalgi R*, and Pilpel Y. 2011. CpG Islands as a putative source for animal miRNAs: evolutionary and functional implications. Mol Biol Evol 28, 1545-1551. *These authors equally contributed to this work.
Shalgi R, Pilpel Y, and Oren M. 2010. Repression of transposable-elements - a microRNA anti-cancer defense mechanism? Trends Genet 26, 253-259.
Christoffersen NR, Shalgi R, Frankel LB, Leucci E, Lees M, Klausen M, Pilpel Y, Nielsen FC, Oren M, and Lund AH. 2010. p53-independent upregulation of miR-34a during oncogene-induced senescence represses MYC. Cell Death Differ 17, 236-245.
Hsp70’s dynamic interaction with translating ribosomes mediates global translational pausing on the vast majority of mRNAs during proteotoxic stress in mammalian cells.