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  1. Book ; Thesis: Engineering of polyketide production routes in the amoeba Dictyostelium discoideum

    Reimer, Christin / Brakhage, Axel. A. / Winckler, Thomas / Nett, Markus

    2022  

    Institution Friedrich-Schiller-Universität Jena
    Author's details by Christin Reimer (M.Sc.)
    Language English ; German
    Size 132, IX Blätter, Illustrationen, Diagramme, 30 cm
    Publishing place Jena
    Publishing country Germany
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Dissertation, Friedrich-Schiller-Universität Jena, 2022
    Note Zusammenfassungen in deutscher und englischer Sprache ; Zeitschriftenaufsätze in englischer Sprache ; Kumulative Dissertation, enthält Zeitschriftenaufsätze. - Tag der Verteidigung: 01.12.2022
    HBZ-ID HT021733273
    Database Catalogue ZB MED Medicine, Health

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    2023 E 369 order for loan Magazin

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  2. Article ; Online: Control of TurboID-dependent biotinylation intensity in proximity ligation screens.

    Garloff, Vera / Krüger, Thomas / Brakhage, Axel / Rubio, Ignacio

    Journal of proteomics

    2023  Volume 279, Page(s) 104886

    Abstract: Proximity biotinylation screens are a widely used strategy for the unbiased identification of interacting or vicinal proteins. The latest generation biotin ligase TurboID has broadened the range of potential applications, as this ligase promotes an ... ...

    Abstract Proximity biotinylation screens are a widely used strategy for the unbiased identification of interacting or vicinal proteins. The latest generation biotin ligase TurboID has broadened the range of potential applications, as this ligase promotes an intense and faster biotinylation, even in subcellular compartments like the endoplasmic reticulum. On the other hand, the uncontrollable high basal biotinylation rates deny the system's inducibility and are often associated with cellular toxicity precluding its use in proteomics. We report here an improved method for TurboID-dependent biotinylation reactions based on the tight control of free biotin levels. Blockage of free biotin with a commercial biotin scavenger reversed the high basal biotinylation and toxicity of TurboID, as shown by pulse-chase experiments. Accordingly, the biotin-blockage protocol restored the biological activity of a bait protein fused to TurboID in the endoplasmic reticulum and rendered the biotinylation reaction inducible by exogenous biotin. Importantly, the biotin-blockage protocol was more effective than biotin removal with immobilized avidin and did not affect the cellular viability of human monocytes over several days. The method presented should be useful to researchers interested in exploiting the full potential of biotinylation screens with TurboID and other high-activity ligases for challenging proteomics questions. SIGNIFICANCE: Proximity biotinylation screens using the last generation biotin ligase TurboID represent a powerful approach for the characterisation of transient protein-protein interaction and signaling networks. However, a constant and high basal biotinylation rate and the associated cytotoxicity often preclude the use of this method in proteomic studies. We report a protocol based on modulation of free biotin levels that prevents the deleterious effects of TurboID while allowing inducible biotinylation, even in subcellular compartments such as the endoplasmic reticulum. This optimised protocol greatly expands the applications of TurboID in proteomic screens.
    MeSH term(s) Humans ; Biotinylation ; Biotin ; Proteomics/methods ; Proteins ; Ligases
    Chemical Substances Biotin (6SO6U10H04) ; Proteins ; Ligases (EC 6.-)
    Language English
    Publishing date 2023-03-24
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2400835-7
    ISSN 1876-7737 ; 1874-3919
    ISSN (online) 1876-7737
    ISSN 1874-3919
    DOI 10.1016/j.jprot.2023.104886
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  3. Article: Fostering students' situational interest in physics

    Brakhage, Henriette / Groeschner, Alexander / Glaeser-Zikuda, Michaela / Hagenauer, Gerda

    Research in Science Education

    Results from a classroom-based intervention study

    2023  Volume 53, Page(s) 993–1008

    Abstract: Research indicates that students' interest in science decreases during their school years. To counteract this, a quasi-experimental instructional intervention was designed in which we addressed students' leisure interests to foster their (situational) ... ...

    Title translation Förderung des situativen Interesses von Schülern an der Physik: Ergebnisse einer klassenbasierten Interventionsstudie. (DeepL)
    Abstract Research indicates that students' interest in science decreases during their school years. To counteract this, a quasi-experimental instructional intervention was designed in which we addressed students' leisure interests to foster their (situational) interest in physics. Students in the intervention group got the opportunity to choose topics matching their leisure interests (e.g. sports, music) and were encouraged to reflect on and discuss the application of principles of semiconductor physics to those topics throughout the intervention with a duration over 11 lessons. The intervention group consisted of 60 students from German high-track schools; another 55 students comprised the control group. The results of a MANCOVA analysis indicate that the instructional intervention succeeded in triggering students' catch and hold component of situational interest during all four phases of the lesson series. Furthermore, behavioural disengagement developed more positively for students in the intervention group, while no significant effects were found for their behavioural engagement, their interest in physics-related activities in leisure or their general interest in physics classes in school. The results suggest that addressing students' leisure interests in physics classes can promote their situational interest and reduce their behavioural disengagement in physics.
    Keywords Einstellungen (Schülerinnen, Schüler und Studierende) ; Engagement (Schülerinnen, Schüler und Studierende) ; Freizeit ; High School Students ; Interessen ; Interests ; Lehrmethoden ; Leisure Time ; Naturwissenschaftlicher Unterricht ; Physics ; Physik ; School Based Intervention ; Schulische Intervention ; Science Education ; Sekundarstufenschülerinnen und Sekundarstufenschüler ; Student Attitudes ; Student Engagement ; Teaching Methods
    Language English
    Document type Article
    ZDB-ID 2065354-2
    ISSN 1573-1898 ; 0157-244X
    ISSN (online) 1573-1898
    ISSN 0157-244X
    DOI 10.1007/s11165-023-10120-x
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  4. Article ; Online: EAM/FEMS launches

    Brakhage, Axel / Buchrieser, Carmen / Horn, Matthias / Traktman, Paula

    microLife

    2020  Volume 1, Issue 1, Page(s) uqaa001

    Language English
    Publishing date 2020-07-08
    Publishing country England
    Document type Editorial
    ISSN 2633-6693
    ISSN (online) 2633-6693
    DOI 10.1093/femsml/uqaa001
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  5. Article: Functional modulation of chemical mediators in microbial communities.

    Stallforth, Pierre / Mittag, Maria / Brakhage, Axel A / Hertweck, Christian / Hellmich, Ute A

    Trends in biochemical sciences

    2022  Volume 48, Issue 1, Page(s) 71–81

    Abstract: Interactions between microorganisms are often mediated by specialized metabolites. Although the structures and biosynthesis of these compounds may have been elucidated, microbes exist within complex microbiomes and chemical signals can thus also be ... ...

    Abstract Interactions between microorganisms are often mediated by specialized metabolites. Although the structures and biosynthesis of these compounds may have been elucidated, microbes exist within complex microbiomes and chemical signals can thus also be subject to community-dependent modifications. Increasingly powerful chemical and biological tools allow to shed light on this poorly understood aspect of chemical ecology. We provide an overview of loss-of-function and gain-of-function chemical mediator (CM) modifications within microbial multipartner relationships. Although loss-of-function modifications are abundant in the literature, few gain-of-function modifications have been described despite their important role in microbial interactions. Research in this field holds great potential for our understanding of microbial interactions and may also provide novel tools for targeted interference with microbial signaling.
    MeSH term(s) Microbiota
    Language English
    Publishing date 2022-08-16
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 194216-5
    ISSN 1362-4326 ; 0968-0004 ; 0376-5067
    ISSN (online) 1362-4326
    ISSN 0968-0004 ; 0376-5067
    DOI 10.1016/j.tibs.2022.07.006
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  6. Article: Influenza Virus-Induced Paracrine Cellular Senescence of the Lung Contributes to Enhanced Viral Load.

    Schulz, Luise / Hornung, Franziska / Häder, Antje / Radosa, Lukáš / Brakhage, Axel A / Löffler, Bettina / Deinhardt-Emmer, Stefanie

    Aging and disease

    2023  Volume 14, Issue 4, Page(s) 1331–1348

    Abstract: Aging is a major risk factor associated with increased morbidity and mortality rates observed during respiratory infections. In this study, we investigated the role of influenza virus infections in the establishment of premature cellular senescence and ... ...

    Abstract Aging is a major risk factor associated with increased morbidity and mortality rates observed during respiratory infections. In this study, we investigated the role of influenza virus infections in the establishment of premature cellular senescence and paracrine macrophage-activated inflammation. We observed in our murine model a premature aging by the appearance of senescent cells in the lungs after 21 d of influenza A virus infection. By using murine ex vivo lung models, the influence of TNF-α on the establishment of cellular senescence was detectable. Our findings were proven by using conditioned media of infected human monocyte-derived macrophages on primary lung fibroblasts. Here, a distinct expression of senescence-associated parameters could be confirmed. Furthermore, senescent cells in the lungs strongly influenced subsequent viral infections. Our data demonstrated a higher viral load in senescent primary lung fibroblasts, indicating an intracellular effect on viral replication. Transcriptomic data revealed an increased regulation of JAK/STAT signaling in senescent IAV-infected cells accompanied with increased TRAIL expression. Additionally, senescent cells indicating low pH values, accelerating viral replication. Our study provides new insights into pathomechanisms of virus-induced cellular senescence. Hence, IAV infection induces premature senescence and subsequent infections in senescent cells lead to an increased viral replication.
    Language English
    Publishing date 2023-08-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2625789-0
    ISSN 2152-5250
    ISSN 2152-5250
    DOI 10.14336/AD.2023.0310
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  7. Article ; Online: Multiple phosphorylation sites regulate the activity of the repressor Mig1 in

    Ramírez-Zavala, Bernardo / Betsova, Darina / Schwanfelder, Sonja / Krüger, Ines / Mottola, Austin / Krüger, Thomas / Kniemeyer, Olaf / Brakhage, Axel A / Morschhäuser, Joachim

    mSphere

    2023  Volume 8, Issue 6, Page(s) e0054623

    Abstract: Importance: The SNF1 protein kinase signaling pathway, which is highly conserved in eukaryotic cells, is important for metabolic adaptations in the pathogenic ... ...

    Abstract Importance: The SNF1 protein kinase signaling pathway, which is highly conserved in eukaryotic cells, is important for metabolic adaptations in the pathogenic yeast
    MeSH term(s) Candida albicans/genetics ; Candida albicans/metabolism ; Phosphorylation ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae/genetics ; Carbon/metabolism
    Chemical Substances Saccharomyces cerevisiae Proteins ; Carbon (7440-44-0)
    Language English
    Publishing date 2023-11-27
    Publishing country United States
    Document type Journal Article
    ISSN 2379-5042
    ISSN (online) 2379-5042
    DOI 10.1128/msphere.00546-23
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  8. Article ; Online: Bacterial secretion systems contribute to rapid tissue decay in button mushroom soft rot disease.

    Wein, Philipp / Dornblut, Katharina / Herkersdorf, Sebastian / Krüger, Thomas / Molloy, Evelyn M / Brakhage, Axel A / Hoffmeister, Dirk / Hertweck, Christian

    mBio

    2023  Volume 14, Issue 4, Page(s) e0078723

    Abstract: The soft rot ... ...

    Abstract The soft rot pathogen
    MeSH term(s) Bacterial Secretion Systems ; Agaricus/genetics ; Oxalobacteraceae ; Fungi ; Bacteria
    Chemical Substances Bacterial Secretion Systems
    Language English
    Publishing date 2023-07-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mbio.00787-23
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  9. Article ; Online: The influenza A virus promotes fungal growth of Aspergillus fumigatus via direct interaction in vitro.

    König, Sarah / Schroeder, Josefine / Nietzsche, Sandor / Heinekamp, Thorsten / Brakhage, Axel A / Zell, Roland / Löffler, Bettina / Ehrhardt, Christina

    Microbes and infection

    2023  Volume 26, Issue 3, Page(s) 105264

    Abstract: Seasonal influenza A virus (IAV) infections still pose a major burden for public health worldwide. Severe disease progression or even death is often related to superinfections of the virus and a secondary bacterial pathogen. However, fungi, especially ... ...

    Abstract Seasonal influenza A virus (IAV) infections still pose a major burden for public health worldwide. Severe disease progression or even death is often related to superinfections of the virus and a secondary bacterial pathogen. However, fungi, especially Aspergillus fumigatus, are also frequently diagnosed during IAV infection. Although, clinical studies have reported the severity of influenza-associated pulmonary aspergillosis, the molecular mechanisms underlying this type of disease are poorly understood. Here, a new in vitro model is introduced that allows the investigation of complex pathogen-host and pathogen-pathogen interactions during coinfection of lung epithelial cells with IAV and A. fumigatus. Our data reveal a reduced IAV load and IAV-induced cytokine and chemokine expression in the presence of A. fumigatus. At the same time, IAV infection promotes the growth of A. fumigatus. Even in the absence of the human host cell, purified IAV particles are able to induce hyphal growth, due to a direct interaction of the virus particles with the fungal surface. Thus, our study gives first insights into the complex interplay between IAV, A. fumigatus and the host cell as well as the two pathogens alone.
    MeSH term(s) Humans ; Aspergillus fumigatus ; Influenza A virus ; Influenza, Human ; Lung/microbiology ; Epithelial Cells
    Language English
    Publishing date 2023-11-24
    Publishing country France
    Document type Journal Article
    ZDB-ID 1465093-9
    ISSN 1769-714X ; 1286-4579
    ISSN (online) 1769-714X
    ISSN 1286-4579
    DOI 10.1016/j.micinf.2023.105264
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  10. Article ; Online: Regulation of fungal secondary metabolism.

    Brakhage, Axel A

    Nature reviews. Microbiology

    2012  Volume 11, Issue 1, Page(s) 21–32

    Abstract: Fungi produce a multitude of low-molecular-mass compounds known as secondary metabolites, which have roles in a range of cellular processes such as transcription, development and intercellular communication. In addition, many of these compounds now have ... ...

    Abstract Fungi produce a multitude of low-molecular-mass compounds known as secondary metabolites, which have roles in a range of cellular processes such as transcription, development and intercellular communication. In addition, many of these compounds now have important applications, for instance, as antibiotics or immunosuppressants. Genome mining efforts indicate that the capability of fungi to produce secondary metabolites has been substantially underestimated because many of the fungal secondary metabolite biosynthesis gene clusters are silent under standard cultivation conditions. In this Review, I describe our current understanding of the regulatory elements that modulate the transcription of genes involved in secondary metabolism. I also discuss how an improved knowledge of these regulatory elements will ultimately lead to a better understanding of the physiological and ecological functions of these important compounds and will pave the way for a novel avenue to drug discovery through targeted activation of silent gene clusters.
    MeSH term(s) Biological Products/metabolism ; Fungi/genetics ; Fungi/metabolism ; Gene Expression Regulation, Fungal ; Genes, Fungal ; Metabolic Networks and Pathways/genetics ; Multigene Family ; Transcription, Genetic
    Chemical Substances Biological Products
    Language English
    Publishing date 2012-11-26
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2139054-X
    ISSN 1740-1534 ; 1740-1526
    ISSN (online) 1740-1534
    ISSN 1740-1526
    DOI 10.1038/nrmicro2916
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