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Bacteria live under ever-changing environmental conditions. To survive and propagate, bacteria sense environmental cues and respond to them quickly allowing for adaptation. Our research aims to unravel novel principles and pathways underlying signal-perception, -transduction and cellular regulation in the model organism Escherichia coli and related bacteria including pathogens. We focus on mechanisms acting at the post-transcriptional level including small RNAs and RNA-binding proteins. Moreover, we study two-component and phosphotransferase systems, which monitor the environment and transduce information into the cell. Specifically, we investigate a regulatory network, which controls cell envelope biosynthesis and repair in response to metabolic signals and extracytoplasmic stress. This network involves the trans-envelope signaling complex QseEGF, which employs a regulatory cascade composed of small RNAs GlmY/GlmZ and the RNA binding protein RapZ to achieve envelope homeostasis.
We are bacterial geneticists and use the whole repertoire of molecular biology methods to address our questions. We are devoted to the power and art of genetic screens that often reveal novel regulatory pathways and factors. For our RNA-based research projects we employ classical methods such as Northern, EMSA or RACE analyses as well as state-of-the-art approaches including RNA-seq, RNA structure probing and pull-down techniques to analyze RNA/protein interactions. Furthermore, the laboratory has a longstanding expertise in analyzing protein phosphorylations and protein-protein interactions using a variety of complementary in vivo and in vitro techniques. Through application of ligand fishing approaches we routinely identify novel interaction partners for our proteins of interest. Structural and biophysical techniques and bioinformatics are applied in the framework of established collaborations.
Boris Görke studied Biology and obtained a PhD at the University of Freiburg, Germany. Boris performed a postdoc at the Laboratoire De Chimie Bacteriénne, CNRS in Marseille, France. Subsequently he moved to the University of Göttingen, Germany where he started his own research group and received the venia legendi for “Microbiology and Genetics”. Since 2013 he is group leader at the Max Perutz Labs
We recently revealed a conserved signaling cascade acting across three different cellular compartments. The outer-membrane lipoprotein QseG activates the inner membrane-bound kinase QseE by interaction to phosphorylate a cytoplasmic response regulator. This three-component system senses a stimulus, likely derived from the cell envelope, to activate genes required for envelope synthesis and repair.
Kinase KdpD can be activated by non-phosphorylated PtsN, a component of the PTS(Ntr), resulting in phosphorylation of response regulator KdpE. Paradoxically, PtsN and KdpE compete for binding as both contact the KdpD transmitter domain. We found that PtsN binds one protomer in the KdpD dimer to stimulate phosphorylation of the second protomer in trans, which finally phosphorylates KdpE.
The RNA-binding protein RapZ is part of a regulatory circuit involving the two homologous small RNAs GlmY and GlmZ, which jointly regulate synthesis of cell envelope precursor molecules. Our recent work on RapZ revealed the structure and features of a novel type of an RNA-binding protein, which allosterically activates endoribonuclease RNase E by interaction to selectively degrade GlmZ on demand.
We recently discovered that small RNAs GlmY and GlmZ provide Enterobacteria including important pathogens with intrinsic resistance towards antibiotics targeting the central cell envelope synthesis enzyme GlmS. Thus, suppression of the GlmY/GlmZ circuit increases antibiotic susceptibility, which could be useful to treat infections and may help to overcome the current antibiotic resistance crisis.
Doris emeruem
Diploma/Master Student
+43-1-4277-74610
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Two Small RNAs Conserved in Enterobacteriaceae Provide Intrinsic Resistance to Antibiotics Targeting the Cell Wall Biosynthesis Enzyme Glucosamine-6-Phosphate Synthase.
Khan MA, Göpel Y, Milewski S, Görke B.
Domain swapping between homologous bacterial small RNAs dissects processing and Hfq binding determinants and uncovers an aptamer for conditional RNase E cleavage.
Göpel, Yvonne; Khan, Muna Ayesha; Görke, Boris
Targeted decay of a regulatory small RNA by an adaptor protein for RNase E and counteraction by an anti-adaptor RNA.
Göpel, Yvonne; Papenfort, Kai; Reichenbach, Birte; Vogel, Jörg; Görke, Boris
Project title: “Signal perception and transduction by small RNAs GlmY and GlmZ" (P26681-B22)”
Our research on small RNAs is supported by the FWF.
The Group Görke participates in the special Doctoral Program "RNA Biology" reviewed and funded by the Austrian Research Fund FWF.
The Görke group participates in the Special Research Area (SFB) "RNA-Reg - RNA regulation of the transcriptome" funded by the Austrian Science Fund FWF. SFB's are peer-reviewed, highly interactive research networks, established to foster long-term, interdisciplinary co-operation of local research groups working on the frontiers of their thematic areas.
Nutrient-regulated control of lysosome function by signaling lipid conversion
Shedding Light on the Dark Side of Terrestrial Ecosystems: Assessing Biogeochemical Processes in Soils
Protein homeostasis and lifelong cell maintenance
Dissecting the turgor sensing mechanisms in the blast fungus Magnaporthe oryzae
Pikobodies: What does it take to bioengineer NLR immune receptor-nanobody fusions
When all is lost? Measuring historical signals
Gene regulatory mechanisms governing human development, evolution and variation
Regulation of Cerebral Cortex Morphogenesis by Migrating Cells
Phage therapy for treating bacterial infections: a double-edged sword
Suckers and segments of the octopus arm
Using the house mouse radiation to study the rapid evolution of genes and genetic processes
CRISPR jumps ahead: mechanistic insights into CRISPR-associated transposons
SLiMs and SHelMs: Decoding how short linear and helical motifs direct PPP specificity to direct signaling
Title to be announced
Visualising mitotic chromosomes and nuclear dynamics by correlative light and electron microscopy
Enigmatic evolutionary origin and multipotency of the neural crest cells - major drivers of vertebrate evolution
Engineered nanocarriers for imaging of small proteins by CryoEM
Bacterial cell envelope homeostasis at the (post)transcriptional level
Title to be announced
Hydrologic extremes alter mechanisms and pathways of carbon export from mountainous floodplain soils
Dissecting post-transcriptional gene expression regulation in humans and viruses
Polyploidy and rediploidisation in stressful times
Prdm9 control of meiotic synapsis of homologs in intersubspecific hybrids
Title to be announced
RNA virus from museum specimens
Programmed DNA double-strand breaks during meiosis: Mechanism and evolution
Title to be announced