Extracellular Vesicles and Diffusable Signals

Prof. Dr. med. Bernd T. Schmeck

Bernd Schmeck has been appointed Adjunct Faculty of the Institute for Lung Health, where he oversees the area of Extracellular Vesicles. He is a full professor for Molecular Pneumology and Infectious Diseases at the University of Marburg, Germany, head of the Institute for Lung Research and the Clinic for Airway Infections at the University Medical Center. He is a member of the German Center for Lung Research (DZL), the German Center for Infectious Diseases Research (DZIF), and the Marburg Center for Synthetic Microbiology (SYNMIKRO).

Bernd Schmeck was born in Siegen and studied medicine at the JLU Giessen and the Charité Medical School in Berlin. After a research stay at King´s College London he pursuit and finished his doctoral thesis with distinction at Humboldt University Berlin. In 2003, he received a research scholarship for pneumonia research. He was visiting scientist at the Johns-Hopkins-University, Baltimore, and Postdoc in lung research at the Charité Medical School in Berlin. In 2008, he was appointed head of the BMBF Junior Research Group “Systems biology of Lung Inflammation”. In 2011, he was appointed full professor at Marburg University, 2013 funding director of the Institute for Lung Research, and 2020 head of the Clinic for Airway Infection. He has served as co-speaker of the European JPIAMR project “Restrict-Pneumo-AMR” as well as the LOEWE consortium Medical RNomics, and was member of the steering committees of BMBF FORSYS and BMBF Capsys. Currently, he his speaker of the LOEWE consortium “Diffusible Signals” (Impact of diffusible signals at human cell-microbe interfaces), and the European ERACoSysMed consortium “Sysmed COPD”. He is project leader of the transregional DFG-Collaborative Research Center “Innate Immunity of the Lung” (SFB/TR84) and faculty member of the international Max Planck Research School (IMPRS) “Principles of Microbial Life: From molecules to cells, from cells to interactions (µLife)”. He published 111 research papers (up to 03/2021) in well-renowned scientific journals such as Nature Microbiology, Nature Communications, Proceedings of the National Academy of Science, Journal of Clinical Investigation, Circulation Research, and the American Journal of Respiratory and Critical Care Medicine.

The Schmeck lab focuses on the intercellular communication between different host cell types and also bacterial cells in lung parenchyma inflammation. Specifically, we address extracellular vesicles from host cell and bacterial origin, their generation, content, uptake, and function, and have established many state-of-the-art and novel technologies for that.

Extracellular vesicles (EVs) constitute an emerging class of diffusible effectors for cellular communication in homeostasis and pathogenicity. They are released from most cell types and can be found in all body fluids. Because they contain a multitude of molecules (nucleic acids, lipids and proteins), which depend on the status of their cell of origin, they can function as biomarkers. Their acquisition requires only minimally invasive procedures, and their content may be useful for the detection and prognosis of diseases.

In the laboratory, EVs are isolated from body fluids and experimental models by size-exclusion chromatography, differential ultracentrifugation, or precipitation techniques. They are analysed by NanoView ExoView technology, imaging flowcytometry (Amnis ImageStream Mk II), nanoparticle tracking analysis, nano-flowcytometry, RNA-sequencing, mass spectrometry (proteomics, metabolomics), and structural biology techniques in cooperation with other platforms.

Figure 1: Technologies applied for extracellular vesicles analysis (by Katrin Bedenbender)

Exemplarily, the group found that EVs in patient plasma are biomarkers for the diagnosis and prognosis of severe respiratory infection. Furthermore, the group analysed EVs from bronchioalveolar lavage (BAL) fluid of influenza-induced ARDS patients and observed an enrichment of microRNA-17a, which causes a repression of Mx1 and subsequent enhanced influenza virus replication in primary human alveolar epithelial cells.

Contact

Prof. Dr. med. Bernd T. Schmeck
Member of the German Center of Lung Research (DZL)
Member of the German Center for Infectious Disease Research (DZIF)

Institute for Lung Research
Philipps University Marburg
Hans-Meerwein-Str. 2
35043 Marburg, Germany

Tel: +49 (0) 06421 28 65713
Fax: +49 (0) 06421 28

Email:
Bernd.schmeck@uni-marburg.de

Web:
www.i-lung.de

 Ten most important publications

1. Herkt CE, Caffrey BE, Surmann K, Blankenburg S, Gesell Salazar M, Jung AL, Herbel SM, Hoffmann K, Schulte LN, Chen W, Sittka-Stark A, Völker U, Vingron M, Marsico A, Bertrams W, Schmeck B. A MicroRNA Network Controls Legionella pneumophila Replication in Human Macrophages via LGALS8 and MX1. mBio. 2020;11(2):e03155-19.
2. Bertrams W, Griss K, Han M, Seidel K, Klemmer A, Sittka-Stark A, Hippenstiel S, Suttorp N, Finkernagel F, Wilhelm J, Greulich T, Vogelmeier CF, Vera J, Schmeck B. Transcriptional analysis identifies potential biomarkers and molecular regulators in pneumonia and COPD exacerbation. Sci Rep. 2020;10(1):241.
3. Lindhauer NS, Bertrams W, Pöppel A, Herkt CE, Wesener A, Hoffmann K, Greene B, Van Der Linden M, Vilcinskas A, Seidel K, Schmeck B. Antibacterial activity of a Tribolium castaneum defensin in an in vitro infection model of Streptococcus pneumoniae. Virulence. 2019;10(1):902-909.
4. Jung AL, Møller Jørgensen M, Bæk R, Griss K, Han M, Auf Dem Brinke K, Timmesfeld N, Bertrams W, Greulich T, Koczulla R, Hippenstiel S, Suttorp N, Schmeck B. Surface Proteome of Plasma Extracellular Vesicles as Biomarkers for Pneumonia and Acute Exacerbation of Chronic Obstructive Pulmonary Disease. J Infect Dis. 2020;221(2):325-335.
5. Scheller N, Herold S, Kellner R, Bertrams W, Jung AL, Janga H, Greulich T, Schulte LN, Vogelmeier CF, Lohmeyer J, Schmeck B. Proviral MicroRNAs Detected in Extracellular Vesicles From Bronchoalveolar Lavage Fluid of Patients With Influenza Virus-Induced Acute Respiratory Distress Syndrome. J Infect Dis. 2019;219(4):540-543
6. Nandakumar R, Tschismarov R, Meissner F, Prabakaran T, Krissanaprasit A, Farahani E, Zhang BC, Assil S, Martin A, Bertrams W, Holm CK, Ablasser A, Klause T, Thomsen MK, Schmeck B, Howard KA, Henry T, Gothelf KV, Decker T, Paludan SR. Intracellular bacteria engage a STING-TBK1-MVB12b pathway to enable paracrine cGAS-STING signalling. Nat Microbiol. 2019;4(4):701-713.
7. Schulz C, Lai X, Bertrams W, Jung AL, Sittka-Stark A, Herkt CE, Janga H, Zscheppang K, Stielow C, Schulte L, Hippenstiel S, Vera J, Schmeck B. THP-1-derived macrophages render lung epithelial cells hypo-responsive to Legionella pneumophila - a systems biology study. Sci Rep. 2017;7(1):11988.
8. Jung AL, Herkt CE, Schulz C, Bolte K, Seidel K, Scheller N, Sittka-Stark A, Bertrams W, Schmeck B. Legionella pneumophila infection activates bystander cells differentially by bacterial and host cell vesicles. Sci Rep. 2017;7(1):6301.
9. Du Bois I, Marsico A, Bertrams W, Schweiger MR, Caffrey BE, Sittka-Stark A, Eberhardt M, Vera J, Vingron M, Schmeck BT. Genome-wide Chromatin Profiling of Legionella pneumophila-Infected Human Macrophages Reveals Activation of the Probacterial Host Factor TNFAIP2. J Infect Dis. 2016;214(3):454-63.
10. Jung AL, Stoiber C, Herkt CE, Schulz C, Bertrams W, Schmeck B. Legionella pneumophila-Derived Outer Membrane Vesicles Promote Bacterial Replication in Macrophages. PLoS Pathog. 2016;12(4):e1005592.

Here you can find all ILH-publications