A5057002790- interferon and immune responses
- Cancer-related molecular mechanisms research
- MicroRNA in disease regulation
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- RNA modifications and cancer
- Neonatal Respiratory Health Research
- Neuroscience of respiration and sleep
- Pneumocystis jirovecii pneumonia detection and treatment
- Respiratory Support and Mechanisms
- Extracellular vesicles in disease
- Legionella and Acanthamoeba research
- RNA and protein synthesis mechanisms
- Antibiotic Resistance in Bacteria
- Escherichia coli research studies
- Bacteriophages and microbial interactions
- RNA regulation and disease
- Heme Oxygenase-1 and Carbon Monoxide
- Vibrio bacteria research studies
- Peroxisome Proliferator-Activated Receptors
- Viral Infections and Immunology Research
- Respiratory viral infections research
- Gut microbiota and health
- Influenza Virus Research Studies
- Autophagy in Disease and Therapy
Philipps University of Marburg
2018-2024
Universities of Giessen and Marburg Lung Center
2018-2020
Institut für Lungenforschung
2018-2020
German Center for Lung Research
2018-2020
Justus-Liebig-Universität Gießen
2018
University of Lübeck
2017
University Hospital Schleswig-Holstein
2017
Influenza A viruses (IAV) and influenza B (IBV) cause significant morbidity mortality during seasonal outbreaks. Cleavage of the viral surface glycoprotein hemagglutinin (HA) by host proteases is a prerequisite for membrane fusion essential virus infectivity. Inhibition relevant provides promising therapeutic approach that may avoid development drug resistance. HA most cleaved at monobasic cleavage site, number have been shown to cleave in vitro . This study demonstrates transmembrane...
The systemic immune response to viral infection is shaped by master transcription factors, such as NF-κB, STAT1, or PU.1. Although long noncoding RNAs (lncRNAs) have been suggested important regulators of factor activity, their contributions the immunopathologies observed during SARS-CoV-2 remained unknown. Here, we employed a targeted single-cell RNA sequencing approach reveal lncRNAs differentially expressed in blood leukocytes severe COVID-19. Our results uncover lncRNA PIRAT...
Influenza A virus (IAV) causes severe respiratory infections and alveolar epithelial damage resulting in acute distress syndrome (ARDS). Extracellular vesicles (EVs) have been shown to mediate cellular crosstalk inflammation by transfer of microRNAs (miRNAs). In this study, we found significant changes the miRNA composition EVs bronchoalveolar lavage fluid from patients with IAV-induced ARDS. Among 9 significantly deregulated microRNAs, miR-17-5p was upregulated patients' BALF IAV-infected...
RNA has been proposed as an important scaffolding factor in the nucleus, aiding protein complex assembly dense intracellular milieu. Architectural contributions of to cytosolic signaling pathways, however, remain largely unknown. Here, we devised a multidimensional gradient approach, which systematically locates components within cellular networks. Among subset noncoding RNAs (ncRNAs) cosedimenting with ubiquitin-proteasome system, our approach unveiled ncRNA MaIL1 critical structural...
The biological and immune-protective properties of surfactant-derived phospholipids phospholipid subfractions in the context neonatal inflammatory lung disease are widely unknown. Using a porcine triple-hit acute respiratory distress syndrome (ARDS) model (repeated airway lavage, overventilation, LPS instillation into airways), we assessed whether supplementation surfactant (S; poractant alfa) with inositol derivatives [inositol 1,2,6-trisphosphate (IP3) or phosphatidylinositol...
Infectious agents such as lipopolysaccharides (LPS) challenge the functional properties of alveolar-capillary barrier (ACB) in lung. In this study, we analyse site-specific effects LPS on ACB and reveal individual cell types a unit. Monocultures H441 epithelial cells co-cultures with endothelial cultured Transwells® were treated from apical or basolateral compartment. Barrier analysed by transepithelial electrical resistance (TEER), transport assays, immunostaining assessment tight...
Infection research routinely employs in vitro cell cultures or vivo mouse models as surrogates of human hosts. Differences between murine and immunity the low level complexity traditional cultures, however, highlight demand for alternative that combine -like properties system with straightforward experimental perturbation. Here, we introduce a 3D tissue model comprising multiple types intestinal barrier, primary site pathogen attack. During infection foodborne Salmonella enterica serovar...
Transgene expression of green fluorescent protein (GFP) has facilitated the spatiotemporal investigation host-pathogen interactions; however, introduction GFP gene remains challenging in drug-resistant bacteria. Herein, we report a novel far-red nucleic acid stain, 6-TramTO-3, which efficiently labels bacteria through DNA binding mode without affecting growth and viability. Exemplarily, stained Klebsiella pneumoniae, major threat to hospitalized patients, deciphered divergent interaction...
CRISPR/Cas9-based approaches have greatly facilitated targeted genomic deletions. Contrary to coding genes however, which can be functionally knocked out by frame-shift mutagenesis, non-coding RNA (ncRNA) gene knockouts remained challenging. Here we present a universal ncRNA knockout approach guided epigenetic hallmarks, enables robust silencing even in provisionally annotated loci. We build on previous work reporting the presence of overlapping histone H3 lysine 4 tri-methylation (H3K4me3)...
Immune response in the lung has to protect huge alveolar surface against pathogens while securing delicate structure. Macrophages and epithelial cells constitute first line of defense together orchestrate initial steps host defense. In this study, we analysed influence macrophages on type II during Legionella pneumophila-infection by a systems biology approach combining experimental work mathematical modelling. We found that L. pneumophila-infected THP-1-derived provoke pro-inflammatory...
The RNA helicase RIG-I plays a key role in sensing pathogen-derived RNA. Double-stranded structures bearing 5'-tri- or diphosphates are commonly referred to as activating ligands. However, endogenous fragments generated during viral infection via RNase L also activate RIG-I. Of note, RNase-digested bear 5'-hydroxyl group and 2',3'-cyclic phosphate. How despite the lack of 5'-phosphorylation has not been elucidated. Here we describe an ligand (eRL) that is derived from internal transcribed...
A persisting obstacle in human immunology is that blood-derived leukocytes are notoriously difficult to manipulate at the RNA level. Therefore, our knowledge about immune-regulatory RNA-networks largely based on tumour cell-line and rodent knockout models, which do not fully mimic leukocyte biology. Here, we exploit straightforward cell penetrating peptide (CPP) chemistry enable efficient loss-of-function phenotyping of regulatory RNAs primary cells. The classical CPP octaarginine (R8)...
Abstract Transgene expression of green fluorescent protein (GFP) has facilitated the spatiotemporal investigation host–pathogen interactions; however, introduction GFP gene remains challenging in drug‐resistant bacteria. Herein, we report a novel far‐red nucleic acid stain, 6‐TramTO‐3 , which efficiently labels bacteria through DNA binding mode without affecting growth and viability. Exemplarily, stained Klebsiella pneumoniae major threat to hospitalized patients, deciphered divergent...
Despite the important functions of PPARγ in various cell types lung, PPARγ-deficiency club cells induces only mild emphysema. Peroxisomes are distributed a similar way as lung and mainly enriched AECII cells. To date, effects on overall peroxisomal compartment its metabolic alterations pulmonary unknown. Therefore, we characterized wild-type cell-specific knockout-mice lungs used C22 to investigate roles distal airway epithelium by means 1) double-immunofluorescence labelling for proteins,...
Influenza A virus (IAV) causes severe respiratory infections and alveolar epithelial damage resulting in acute distress syndrome (ARDS). Extracellular vesicles (EV) have been shown to mediate cellular crosstalk inflammation by transfer of microRNAs. In this study, we found significant changes the miRNA composition EVs broncho-alveolar lavage fluid (BALF) from patients with IAV-induced ARDS. Among nine significantly deregulated microRNAs, miR-17-5p was upregulated patientsʼ BALF, IAV-infected...
Die Immunreaktion der Lunge muss die große Alveolaroberfläche verteidigen, andererseits aber delikate Lungenstruktur bewahren. Makrophagen und Lungenepithelzellen orchestrieren initiale Infektabwehr. In dieser Studie untersuchten wir den Einfluss von auf Typ II Alveolarepithelzellen während bakteriellen Infektion. Es zeigte sich, dass bakteriell infizierte pro-inflammatorische Aktivierung benachbarter verursachen, gleichzeitig auch deren Reaktivität gegenüber einer direkten Infektion mit dem...
This protocol describes how to knockout mammalian non-coding RNA genes through excision of an epigenetic transcriptional start site (TSS) signature. To this end two guideRNAs are cloned onto the pX458 CRISPR vector induce DNA cleavage right up- and downstream TSS element. The generate homozygous cell clones. Optionally, successful target by dual guideRNA construct may be pre-validated transfection into easy-to-transfect line (e.g. Hek293) genomic PCR without prior single clonal expansion.
Abstract The systemic immune response to viral infection is shaped by master transcription factors such as NFκB or PU.1. Although long non-coding RNAs (lncRNAs) have been suggested important regulators of factor activity, their contributions the immunopathologies observed during SARS-CoV-2 remained unknown. Here, we employed a targeted single-cell RNA-seq approach reveal lncRNAs differentially expressed in blood leukocytes severe COVID-19. Our results uncover lncRNA PIRAT major PU.1...