65 64 Principal Scientist Profiles Axel Brakhage Axel Brakhage Principal Scientist Profiles PROFESSOR OF MICROBIOLOGY AND MOLECULAR BIOLOGY, INSTITUTE OF MICROBIOLOGY Axel Brakhage is the scientific director of the Leibniz Institute for Natural Product Research and Infection Biology (HKI) and head of the department of Molecular and Applied Microbiology. Since 2004 he holds a Chair of Microbiology and Molecular Biology at the Institute of Microbiology. He coordinates the Excellence Cluster “Balance of the Microverse”, the CRC/TR 124“Pathogenic fungi and their human host – FungiNet” and the BMBF consortium InfectControl. He is a member of the board of the Leibniz Institute for Photonic Technologies in Infection Research (LPI). He is an elected member and senator of the National Academy of Sciences Leopodina. Currently, he serves as vicepresident the German Research Foundation (DFG). He is member of several scientific advisory boards. AXEL BRAKHAGE RESEARCH AREAS Prof. Brakhage’s research focuses on all aspects of the pathobiology of the human pathogenic fungus Aspergillus fumigatus and on the molecular biology/ biotechnology of fungal natural products and related microbial communication, including: pathogenicity determinants, interaction with the immune system, immune evasion, systems biology of fungal infection, proteome and transcriptome analyses, transcription factors, the activation of silent gene clusters using genetic engineering, drug discovery and antibiotics, histone modifications, microbial communication such as interaction of fungi and bacteria leading to the activation of silent gene clusters with the production of novel compounds; molecular mechanisms of cross talk. TEACHING FIELDS Prof. Brakhage’s teaching is devoted to the early involvement of young scientists in research, as well as to the education of postgraduates. He gives courses in: • Applied microbiology and molecular biology • Molecular biotechnology/ infection biology of lower eukaryotes RESEARCH METHODS The laboratory led by Prof. Brakhage offers methods for the characterization of immune effector cells, the molecular biology of fungi, biochemistry and biotechnology: • 2D-gel electrophoresis and MALDI-TOF/ TOF mass spectrometry, proteomics • Fluorescence and confocal laser scanning microscopy, cell culture techniques • Plasmon resonance spectroscopy • Murine infection models, analysis of immune cells • Isolation of compounds, transcriptome analyses RECENT RESEARCH RESULTS Axel Brakhage’s group has been investigating the pathobiology of the human-pathogenic fungus Aspergillus fumigatus for which the first pathogenicity determinant, dihydroxynaphthalene (DHN) melanin, was discovered. This determinant has major effects on the intracellular processing and apoptosis of human immune effector cells, at least in part by modifying lipid rafts of the phagolysosmal membrane. During this work, the group also contributed to the discovery of a human receptor sensing DHN melanin and of Th17 cells directed against A. fumigatus, that are induced almost exclusively by crossreactivity to Candida albicans. Recently, it was also found that A. fumigatus induces the formation of extracellular antifungal vesicles in human neutrophils [1, 2, 3, 4]. His group has been working on the regulation of the biosyntheses of fungal natural products, many of them being important drugs. His group showed that fungal silent gene clusters are induced by microbial communication, i.e., triggered by a specific bacterium [5]. His work has opened up the possibilities for further investigation of these thus far untapped reservoirs for drug development purposes. This research also contributes to the understanding of how microorganisms communicate with each other. The group has been applying methods of functional genome analysis such as proteome and transcriptome analyses. HOST IMMUNE EVASION TACTICS OF PATHOGENIC FUNGI Human pathogenic microorganisms have evolved a multitude of different immune evasion strategies for establishing their pathogenic lifestyle inside the host. The pathogen mimics or alters host structures, thereby preventing or at least diminishing the host structure’s immune response. Professional phagocytes are often the target of manipulation by intruding microorganisms. Only little is known about how filamentous fungi avoid intracellular killing by phagocytes. Aspergillus fumigatus represents an important airborne fungal pathogen: it is the primary causative agent of invasive aspergillosis in immunocompromised patients. In lung alveoli, resident alveolar macrophages belong to the first line of defence against inhaled conidia. We could show that, depending on dihydroxynaphthalene (DHN)-melanin, the grey green conidial pigment, A. fumigatus prevents formation of flotillin-dependent lipid rafts in phagolysosomal membranes. This leads to reduced vATPase assembly on phagolysosomal membranes and thus reduced acidification of phagolysosomes, in which the pathogen can then survive for a certain time. Our data suggests that pathogenic fungi manipulate host cells to generate a niche, allowing them to survive. [1] Schmidt et al., Cell Reports 32, 108017 (2020). [2] Shopova et al., mBio 11, e00596-20 (2020). [3] Bacher et al., Cell 176, 1340 (2019). [4] Stappers et al., Nature 555, 382 (2018). [5] Stroe et al., eLife 9, e5254 (2020). Contact: Phone: + 49 3641 532-1001 Email: axel.brakhage@uni-jena.de
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