A5040688806- RNA and protein synthesis mechanisms
- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- CRISPR and Genetic Engineering
- Insect and Pesticide Research
- Insect and Arachnid Ecology and Behavior
- Multiple Myeloma Research and Treatments
- Plant and animal studies
- Genomics and Phylogenetic Studies
- RNA Research and Splicing
- Salmonella and Campylobacter epidemiology
- RNA regulation and disease
- Pain Management and Treatment
- Nerve injury and regeneration
- Nerve Injury and Rehabilitation
- Genetics, Bioinformatics, and Biomedical Research
- Protein Degradation and Inhibitors
- Melanoma and MAPK Pathways
- Bariatric Surgery and Outcomes
- Peripheral Nerve Disorders
- Viral Infections and Immunology Research
- Helicobacter pylori-related gastroenterology studies
- Insect symbiosis and bacterial influences
- Autophagy in Disease and Therapy
- Animal Genetics and Reproduction
University of Würzburg
2015-2025
Universitätsklinikum Würzburg
2019-2024
University of Freiburg
2014
ABSTRACT While the model organism Escherichia coli has been subject of intense study for decades, full complement its RNAs is only now being examined. Here we describe a survey E. transcriptome carried out using differential RNA sequencing (dRNA-seq) approach, which can distinguish between primary and processed transcripts, an automated prediction algorithm transcriptional start sites (TSS). With criterion expression under at least one three growth conditions examined, predicted 14,868 TSS...
The molecular roles of many RNA-binding proteins in bacterial post-transcriptional gene regulation are not well understood. Approaches combining vivo UV crosslinking with RNA deep sequencing (CLIP-seq) have begun to revolutionize the transcriptome-wide mapping eukaryotic protein target sites. We applied CLIP-seq chart landscape two major regulators, Hfq and CsrA, model pathogen Salmonella Typhimurium. By detecting binding sites at single-nucleotide resolution, we identify preferences...
Cellular RNAs guide CRISPR-Cas9 The Cas9 nuclease widely used for genome editing is derived from natural bacterial defense systems that protect against invading viruses. directed by RNA guides to cut matching viral DNA. Jiao et al. discovered can also originate cellular unassociated with (see the Perspective Abudayyeh and Gootenberg). They rendered this process programmable, linking presence of virtually any cutting DNA Cas9. This capability basis a new CRISPR diagnostic method developed...
The widespread CsrA/RsmA protein regulators repress translation by binding GGA motifs in bacterial mRNAs. CsrA activity is primarily controlled through sequestration multiple small regulatory RNAs. Here we investigate control the absence of antagonizing RNAs examining regulon human pathogen Campylobacter jejuni. We use genome-wide co-immunoprecipitation combined with RNA sequencing to show that binds flagellar mRNAs and identify major flagellin mRNA (flaA) as main target. flaA...
Antigen-specific neuroinflammation and neurodegeneration are characteristic for neuroimmunological diseases. In Parkinson's disease (PD) pathogenesis, α-synuclein is a known culprit. Evidence α-synuclein-specific T cell responses was recently obtained in PD. Still, causative link between these dopaminergic had been lacking. We thus addressed the functional relevance of immune PD mouse model. utilized model which an Adeno-associated Vector 1/2 serotype (AAV1/2) expressing human mutated...
Abstract Bacterial small proteins impact diverse physiological processes, however, technical challenges posed by size hampered their systematic identification and biochemical characterization. In our quest to uncover relevant for Salmonella pathogenicity, we previously identified YjiS, a 54 amino acid protein, which is strongly induced during this pathogen’s intracellular infection stage. Here, set out further characterize the role of YjiS. Cell culture assays with mutants lacking or...
Abstract The RNA chaperone Hfq plays crucial roles in bacterial gene expression and is a major facilitator of small regulatory (sRNA) action. toroidal architecture the hexamer presents three well-characterized surfaces that allow it to bind sRNAs stabilize them engage target transcripts. Hfq-interacting are categorized into two classes based on they use Hfq. By characterizing systematic alanine mutant library identify amino acid residues impact survival Escherichia coli experiencing nitrogen...
Homeostatic calcium ion (Ca 2+ ) fluxes between the endoplasmic reticulum, cytosol, and extracellular space occur not only in response to cell stimulation but also unstimulated cells. Using murine astrocytes as a model, we asked whether there is signaling function of these resting Ca -fluxes. The data showed that reticulum (ER) depletion, induced by sarcoplasmic/endoplasmic -ATPase (SERCA) inhibition, resulted prolonged influx mitochondrial fragmentation within 10 30 minutes. This could be...
CRISPR-Cas is a sophisticated defence system used by bacteria and archaea to fend off invaders. systems vary in their Cas protein composition have therefore been divided into different classes types. Type I of shown contain the small Cas11 as part interference complex known Cascade. Here we show for first time that an archaeal type I-B also contains homolog Cas11. The Cas11b protein, encoded cas8b gene Haloferax volcanii, represents case internal in-frame translation protein. Translation...
Campylobacter jejuni is currently the most common cause of bacterial gastroenteritis worldwide. However, its genome provides few clues about how it interacts with host. Moreover, infection screens have often been limited to classical cell culture or animal models. To identify C. genes involved in host interactions, we applied transposon sequencing a humanized 3D intestinal model based on tissue engineering. This revealed key proteins required for adherence and/or internalization, including...
Salmonella virulence chiefly relies upon two major pathogenicity islands, SPI-1 and SPI-2, which enable host cell invasion intracellular survival, respectively. There has been increasing evidence for post-transcriptional control of SPI gene expression by Hfq-dependent small RNAs (sRNAs) such as PinT. This 80-nucleotide sRNA is highly expressed after enters cells modulates the transition from to SPI-2 program targeting different factor mRNAs. It elusive, however, how PinT activity could be...
FinO-domain proteins are a widespread family of bacterial RNA-binding with regulatory functions. Their target spectrum ranges from single RNA pair, in the case plasmid-encoded FinO, to global regulons, as enterobacterial ProQ. To assess whether FinO domain itself is intrinsically selective or promiscuous, we determine vivo targets Neisseria meningitidis, which consists solely domain. UV-CLIP-seq identifies associations 16 small non-coding sRNAs and 166 mRNAs. Meningococcal ProQ predominantly...
A full understanding of the contribution small RNAs (sRNAs) to bacterial virulence demands knowledge their target suites under infection-relevant conditions. Here, we take an integrative approach capturing targets Hfq-associated sRNA PinT, a known post-transcriptional timer two major programs Salmonella enterica. Using MS2 affinity purification and RNA sequencing (MAPS), identify PinT ligands in bacteria vitro conditions mimicking specific stages infection cycle growing inside macrophages....
Head and neck squamous cell carcinoma (HNSCC) is known to overexpress a variety of receptor tyrosine kinases, such as the HGF Met. Like other malignancies, HNSCC involves mutual interaction between tumor cells surrounding tissues cells. We hypothesized that activation HGF/Met signaling in influences glucose metabolism therefore substantially changes microenvironment. To determine effect HGF, we submitted three established lines mRNA sequencing. Dynamic were measured real time by an...
Background: Daptomycin represents a reserve antibiotic effective against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). resistance (DAP-R) and clinical treatment failure has been associated with adaptive chromosomal mutations, but so far not acquisition of specific genes. We previously isolated Staphylococcus/Mammaliicoccus sciuri strain TS92, which displays high-level DAP-R lacks reported mutations.Methods: To identify the underlying mechanism, we...
Bacterial small noncoding RNAs (sRNAs) play posttranscriptional regulatory roles in cellular responses to changing environmental cues and adaptation harsh conditions. Generally, the RNA-binding protein Hfq helps sRNAs associate with target mRNAs modulate their translation modify global RNA pools depending on physiological state. Here, a combination of vivo UV cross-linking immunoprecipitation followed by high-throughput sequencing (CLIP-seq) total RNA-seq showed that interacts different...
How homeostatic ER calcium fluxes shape cellular signals is still poorly understood. Here we used dual-color imaging (ER-cytosol) and transcriptome analysis to link candidates of the toolkit astrocytes with signals. We found molecular pharmacological evidence that P/Q-type channel Cacna1a contributes depolarization-dependent entry in astrocytes. For stimulated release, cells express phospholipase Cb3, IP3 receptors Itpr1 Itpr2, but no ryanodine (Ryr1–3). After IP3-induced Stim1/2 – Orai1/2/3...
Abstract Damage to thinly myelinated and unmyelinated nerve fibers causes small fiber pathology, which is increasingly found in pain syndromes such as neuropathy (SFN) fibromyalgia syndrome (FMS). The peripheral endings of the terminate within epidermis, where they are surrounded by keratinocytes that may act primary nociceptive transducers. We performed RNA sequencing obtained from patients with SFN, FMS, healthy controls. 141 deregulated protein coding genes between SFN controls no...
CRISPR-Cas systems provide bacteria with adaptive immunity against phages and plasmids; however, pathways regulating their activity are not well defined. We recently developed a high-throughput genome-wide method (SorTn-seq) used this to uncover regulators. Here, we demonstrate that the widespread Rsm/Csr pathway regulates expression of multiple in Serratia (type I-E, I-F III-A). The main component, RsmA (CsrA), is an RNA-binding post-transcriptional regulator carbon utilisation, virulence...