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A healthy proteome is critical for every organism. Cells constantly need to monitor their proteins and respond to physiological and pathological conditions that perturb the delicate balance between protein synthesis, folding and degradation. In the endoplasmic reticulum (ER), the protein-folding homeostasis is surveyed by a conserved signaling network called the unfolded protein response (UPR). The main purpose of the UPR is to adjust the ER’s folding capacity. How sensors and transducers detect protein-folding problems and mount an appropriate response is a major open question.
In my lab, we seek to understand the UPR at a mechanistic level. We combine cell biology and biochemistry to dissect how cells maintain a protein-folding homeostasis in the ER. Using next generation sequencing and proteomic approaches, we obtain global information on the molecular components regulating ER-quality control. We then reconstitute these processes biochemically and apply structural methods to dissect their working principles at atomic resolution. Our long-term goal is to use the mechanistic insights derived from these approaches to restore protein homeostasis in variety human diseases caused by protein misfolding.
Elif Karagöz majored Molecular Biology and Genetics with a minor in Chemistry at the Middle East Technical University in Turkey. She got her Master’s degree in Molecular Biology at the Max Planck Research School in Göttingen. After completing her PhD at Utrecht University in the group of Stefan Rüdiger, she did a postdoc at Peter Walter’s lab at the University of California San Francisco.
The UPR sensors directly detect unfolded proteins accumulating in the ER as activating ligands. ER-chaperones also bind the UPR sensors and regulate their activation/deactivation dynamics. In my lab, we dissect how the interplay among unfolded proteins, sensors and chaperones tunes the UPR using biochemical, structural, and cell biology approaches.
Protein synthesis and folding is tightly coupled to allow error-free assembly of the proteome. Posttranscriptional regulation provides rapid and reversible means for tuning protein synthesis, yet the mechanisms regulating the fate of ER-targeted mRNAs during protein folding stress remain largely unknown. To this end, we aim to reveal how translation and stability of ER-targeted mRNAs are regulated to maintain ER homeostasis.
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The unfolded protein response and endoplasmic reticulum protein targeting machineries converge on the stress sensor IRE1.
Acosta-Alvear, Diego; Karagöz, Gülsün Elif; Fröhlich, Florian; Li, Han; Walther, Tobias C; Walter, Peter
An unfolded protein-induced conformational switch activates mammalian IRE1.
Karagöz, G Elif; Acosta-Alvear, Diego; Nguyen, Hieu T; Lee, Crystal P; Chu, Feixia; Walter, Peter
Hsp90-Tau complex reveals molecular basis for specificity in chaperone action.
Karagöz, G Elif; Duarte, Afonso M S; Akoury, Elias; Ippel, Hans; Biernat, Jacek; Morán Luengo, Tania; Radli, Martina; Didenko, Tatiana; Nordhues, Bryce A; Veprintsev, Dmitry B; Dickey, Chad A; Mandelkow, Eckhard; Zweckstetter, Markus; Boelens, Rolf; Madl, Tobias; Rüdiger, Stefan G D
Systematic identification and functional characterization of transcriptional regulators
The mineralosphere as microhabitat for microbe, mineral and organic matter interaction in soils
Activation and regulation of plant immunity by secreted signaling peptides
Transcription start site selection is environmentally controlled to diversify the proteome in eukaryotes
How evolutionary interplay between sexes can help us define phenotypes and develop drugs
Mining for protein-protein interactions with AlphaFold: Lessons from Genome Maintenance
Title to be announced
The magical Martian Methane mystery and other stories about life on Mars
Probing life at the nanoscale - one molecule at a time
The Underworld of Deep-Sea Hydrothermal Vents
Epigenetic regulation of germline development
Sister chromatid cohesion is mediated by individual cohesin complexes
Origin and evolution of a defensive symbiosis in tortoise leaf beetles
Capturing conformational transitions in the ubiquitin conjugation cascade
18th Microsymposium on RNA Biology
The „Microsymposium on RNA Biology“ is an international conference that brings together young scientists, junior and senior group leaders, and company representatives from all over the world to present and discuss their latest findings in the exciting field of small RNAs and beyond. The Microsymposium was founded in 2005 and has established itself as the major small RNA meeting in Europe. It is organized by the four research institutions IMBA, IMP, GMI and the Max Perutz Labs as well as by the RNA community of the Vienna BioCenter.
Transformation Reactions of Organic Contaminants and Oxygen: From Field Sites to Reaction Mechanisms
Title to be announced
Multiscale plant bioimaging using advanced microscopy
Evading ageing: Mitochondrial and proteostatic adaptations in oocytes
Parthenogenesis, cryptobiosis, and the survival in extreme environmental conditions
Ubiquitin & Friends Symposium 2024
The Ubiquitin & Friends Symposium is an annual international meeting taking place in the beautiful capital of Austria, aiming to bring together scholars from various fields studying ubiquitin/Ubl biology and protein degradation in a personal, family-like atmosphere, as suggested by the name.
Genomes in Rhodnius prolixus symbiotic system
Stem cells, immune evasion and metastasis in colorectal cancer
The evolution and development of mollusc shells
Unraveling the Complexity of Crossover Regulation in C. elegans
Dynamics of 3D Genome Structure and Function
How superworms can help to solve our plastic waste crisis
New players in an old pathway: biology of methanogens of the TACK superphylum
Shaping morphogen gradients: from molecules to tissues and back
Studying stressed cells by in situ structural biology
Exploring Microbial Resilience: Unravelling Escherichia coliand#x27;s Stress Response at the Level of Protein Synthesis
Deep homology and deep diversity: Evolving genetic toolkits for making and sensing light
The evolution of cell type identity and tissue microecology at the fetal-maternal interface
The unanticipated roles of PICIs and phages in bacterial evolution
Origin and diversification of gut-derived organs in chordates
Job's Dilemma for the Genome: Why Bad Things Happen to Good Chromosomes
Connections between carbon and nitrogen cycling in the ocean
Understanding how the DNA-loop-extruding protein complex Condensin folds a chromatinized genome into mitotic chromosomes
From Roads to Rivers? Occurrence and environmental fate of tire and road wear particles and of tire-related chemicals
Striking physiology and cell biology of (marine) environmental microorganisms
Mechanisms controlling maintenance of cohesin dependent loops
Title to be announced