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Institute: search.filters.UBSInstitut.Fakultätsübergreifend / Sonstige EinrichtungAuthor: search.filters.author.Feuer, Ronny

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    Rapid sampling of Escherichia coli after changing oxygen conditions reveals transcriptional dynamics
    (2017) Wulffen, Joachim von; Ulmer, Andreas; Jäger, Günter; Sawodny, Oliver; Feuer, Ronny
    Escherichia coli is able to shift between anaerobic and aerobic metabolism by adapting its gene expression, e.g., of metabolic genes, to the new environment. The dynamics of gene expression that result from environmental shifts are limited, amongst others, by the time needed for regulation and transcription elongation. In this study, we examined gene expression dynamics after an anaerobic-to-aerobic shift on a short time scale (0.5, 1, 2, 5, and 10 min) by RNA sequencing with emphasis on delay times and transcriptional elongation rates (TER). Transient expression patterns and timing of differential expression, characterized by delay and elongation, were identified as key features of the dataset. Gene ontology enrichment analysis revealed early upregulation of respiratory and iron-related gene sets. We inferred specific TERs of 89 operons with a mean TER of 42.0 nt/s and mean delay time of 22.4 s. TERs correlate with sequence features, such as codon bias, whereas delay times correlate with the involvement of regulators. The presented data illustrate that at very short times after a shift in oxygenation, extensional changes of the transcriptome, such as temporary responses, can be observed. Besides regulation, TERs contribute to the dynamics of gene expression.
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    Model-based characterization of inflammatory gene expression patterns of activated macrophages
    (2016) Rex, Julia; Albrecht, Ute; Ehlting, Christian; Thomas, Maria; Zanger, Ulrich M.; Sawodny, Oliver; Häussinger, Dieter; Ederer, Michael; Feuer, Ronny; Bode, Johannes G.
    Macrophages are cells with remarkable plasticity. They integrate signals from their microenvironment leading to context-dependent polarization into classically (M1) or alternatively (M2) activated macrophages, representing two extremes of a broad spectrum of divergent phenotypes. Thereby, macrophages deliver protective and pro-regenerative signals towards injured tissue but, depending on the eliciting damage, may also be responsible for the generation and aggravation of tissue injury. Although incompletely understood, there is emerging evidence that macrophage polarization is critical for these antagonistic roles. To identify activation-specific expression patterns of chemokines and cytokines that may confer these distinct effects a systems biology approach was applied. A comprehensive literature-based Boolean model was developed to describe the M1 (LPS-activated) and M2 (IL-4/13-activated) polarization types. The model was validated using high-throughput transcript expression data from murine bone marrow derived macrophages. By dynamic modeling of gene expression, the chronology of pathway activation and autocrine signaling was estimated. Our results provide a deepened understanding of the physiological balance leading to M1/M2 activation, indicating the relevance of co-regulatory signals at the level of Akt1 or Akt2 that may be important for directing macrophage polarization.
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    Selective gene expression profiling contributes to a better understanding of the molecular pathways underlying the histological changes observed after RHMVL
    (2022) Arlt, Janine; Vlaic, Sebastian; Feuer, Ronny; Thomas, Maria; Settmacher, Utz; Dahmen, Uta; Dirsch, Olaf
    Background. In previous studies, five vasoactive drugs were investigated for their effect on the recovery process after extended liver resection without observing relevant improvements. We hypothesized that an analysis of gene expression could help to identify potentially druggable pathways and could support the selection of promising drug candidates. Methods. Liver samples obtained from rats after combined 70% partial hepatectomy and right median hepatic vein ligation ( n  = 6/group) sacrificed at 0 h, 24 h, 48 h, and 7days were selected for this study. Liver samples were collected from differentially perfused regions of the median lobe (obstruction-zone, border-zone, normal-zone). Gene expression profiling of marker genes regulating hepatic hemodynamics, vascular remodeling, and liver regeneration was performed with microfluidic chips. We used 3 technical replicates from each sample. Raw data were normalized using LEMming and differentially expressed genes were identified using LIMMA. Results. The strongest differences were found in obstruction-zone at 24 h and 48 h postoperatively compared to all other groups. mRNA expression of marker genes from hepatic hemodynamics pathways (iNOS,Ptgs2,Edn1) was most upregulated. Conclusion. These upregulated genes suggest a strong vasoconstrictive effect promoting arterial hypoperfusion in the obstruction-zone. Reducing iNOS expression using selective iNOS inhibitors seems to be a promising approach to promote vasodilation and liver regeneration.