Topic: Molecular switches regulating stress granule oscillation during RNA virus infection (collaborative project with Alessia Ruggieri within the Heidelberg-Berlin Transregio TRR 186 „Molecular Switches in the Spatio-Temporal Control of Cellular Signal Transmission“)
Stress granules (SGs) are cytosolic aggregates of stalled translation pre-initiation complexes that form under various stress conditions, including virus infection. SGs participate in controlling protein synthesis and are generally thought to have a cytoprotective function. Recently, we discovered that infection with hepatitis C virus (HCV) and other RNA viruses induces an oscillating host cell stress response characterized by cycles of SG assembly and disassembly (1). We identified protein kinase K (PKR) and GADD34 as two main switches that regulate SG oscillation by controlling the phosphorylation status of eIF2. The goal of this project is to quantify the spatio-temporal expression of GADD34 and provide experimental evidence for its oscillation using live-cell imaging microscopy. Moreover, the successful applicant will characterize novel candidate kinases identified in a screen as potential regulators of SG oscillation during HCV infection, including kinases involved in cell cycle control and inflammation. An important goal of the project is to determine whether SGs serve an anti- or pro-vial function during chronic HCV infection.
Application for this position is online through the HBIGS graduate school (Stoecklin0116).
Selected publications of the Stoecklin group:
- Schott et al. Translational regulation of specific mRNAs controls feedback inhibition and survival during macrophage activation. PLoS Genet. 2014;10(6):e1004368.
- Leppek et al. Roquin promotes constitutive mRNA decay via a conserved class of stem-loop recognition motifs. Cell 2013;153:869-81.
- Hofmann et al. Translation suppression promotes stress granule formation and cell survival in response to cold shock. Mol Biol Cell. 2012; 23(19):3786-3800.
- Spasic et al. Genome-wide assessment of AU-rich elements by the AREScore algorithm. PLoS Genet. 2012;8(1):e1002433.
- Sandler et al. Not1 mediates recruitment of the deadenylase Caf1 to RNAs targeted for degradation by tristetraprolin. Nucleic Acids Res. 2011;39(10):4373-86.