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Enhanced Resolution Confocal Laser Scanning Microscope

English title Enhanced Resolution Confocal Laser Scanning Microscope
Applicant Hilbi Hubert
Number 170811
Funding scheme R'EQUIP
Research institution Institut für Medizinische Mikrobiologie Universität Zürich
Institution of higher education University of Zurich - ZH
Main discipline Experimental Microbiology
Start/End 01.10.2017 - 30.09.2018
Approved amount 365'000.00
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All Disciplines (2)

Discipline
Experimental Microbiology
Medical Microbiology

Keywords (5)

hematology; infectiology; medical microbiology; imaging; confocal laser scanning microscope

Lay Summary (German)

Lead
Hochauflösende bildgebende Verfahren sind ein zentraler Bestandteil der modernen medizinisch-biologischen Forschung. Konfokale Laser-Scanning Mikroskopie wird routinemässig eingesetzt, um Fluoreszenz-markierte pathogene Bakterien, Zellen und Gewebe mit grosser Auflösung, Geschwindigkeit und Sensitivität zu analysieren. Eine neue Generation von Detektoren ermöglicht eine bislang unerreichte räumliche und zeitliche Auflösung von biologischen Vorgängen.
Lay summary

Das für dieses Projekt erworbene hochauflösende konfokale Laser-Scanning Mikroskop weist sensitive Detektoren auf, kann Proben schnell und mit geringer Phototoxizität analysieren und ermöglicht, Durchlichtaufnahmen mit hohem Kontrast zu erzeugen sowie Fluoreszenzfarbstoffe in einem breiten Spektrum anzuregen. Diese Eigenschaften des Mikroskops erlauben es, pathogene Bakterien und lebende Zellen sowie Gewebe und vollständige Organe unter kontrollierten Umgebungsbedingungen mit grosser Auflösung, Geschwindigkeit und Sensitivität zu analysieren.

Zentrale Studien dieses Projekts befassen sich mit den Wechselwirkungen von Wirtszellen mit pathogenen Bakterien (Legionellen, Mykobakterien, Staphylokokken), welche respiratorische Krankheiten (Lungenentzündung, Tuberkulose) oder systemische Infektionen („Blutvergiftung“) verursachen. Um den intrazellulären Verlauf der Infektionen mikroskopisch zu analysieren, werden sowohl die Bakterien als auch die Wirtszellen mit fluoreszierenden Markern versehen. Diese bildgebenden Studien geben Aufschluss über die Virulenz der Bakterien und den Pathomechanismus der Infektionen. Letztendliches Ziel der Arbeiten ist es, effizientere Therapiemöglichkeiten gegen humanpathogene Bakterien zu entwickeln.

In weiteren Studien des Projekts werden grundlegende zellbiologische Prozesse im Modellorganismus Bäckerhefe mikroskopisch untersucht. Hier steht vorallem die Analyse der Proteinproduktion (Translation) als zentraler und essentieller Vorgang jeder Zelle im Vordergrund. Ausserdem wird in einer Studie die Blutzellbildung (Hämatopoiese) im Knochenmark untersucht, wofür hochauflösende Mikroskopie von grösseren Flächen notwendig ist. Insgesamt wird das hochauflösende Konfokal-Mikroskop dazu beitragen, zentrale medizinisch-biologisch relevante Prozesse aufzuklären.

Direct link to Lay Summary Last update: 12.09.2017

Responsible applicant and co-applicants

Publications

Publication
Quantitative spatial analysis of haematopoiesis-regulating stromal cells in the bone marrow microenvironment by 3D microscopy
Gomariz Alvaro, Helbling Patrick M., Isringhausen Stephan, Suessbier Ute, Becker Anton, Boss Andreas, Nagasawa Takashi, Paul Grégory, Goksel Orcun, Székely Gábor, Stoma Szymon, Nørrelykke Simon F., Manz Markus G., Nombela-Arrieta César (2018), Quantitative spatial analysis of haematopoiesis-regulating stromal cells in the bone marrow microenvironment by 3D microscopy, in Nature Communications, 9(1), 2532-2532.
Quantitative Imaging Flow Cytometry of Legionella -Infected Dictyostelium Amoebae Reveals the Impact of Retrograde Trafficking on Pathogen Vacuole Composition
Welin Amanda, Weber Stephen, Hilbi Hubert (2018), Quantitative Imaging Flow Cytometry of Legionella -Infected Dictyostelium Amoebae Reveals the Impact of Retrograde Trafficking on Pathogen Vacuole Composition, in Applied and Environmental Microbiology, 84(11), e00158-18.
The large GTPase atlastin controls ER remodeling around a pathogen vacuole
Steiner Bernhard, Weber Stephen, Kaech Andres, Ziegler Urs, Hilbi Hubert (2018), The large GTPase atlastin controls ER remodeling around a pathogen vacuole, in Communicative & Integrative Biology, 11(2), 1-5.
Structure of a eukaryotic cytoplasmic pre‐40S ribosomal subunit
Scaiola Alain, Peña Cohue, Weisser Melanie, Böhringer Daniel, Leibundgut Marc, Klingauf‐Nerurkar Purnima, Gerhardy Stefan, Panse Vikram Govind, Ban Nenad (2018), Structure of a eukaryotic cytoplasmic pre‐40S ribosomal subunit, in The EMBO Journal, 37(7), e98499-e98499.
Acanthamoeba and Dictyostelium as Cellular Models for Legionella Infection
Swart A. Leoni, Harrison Christopher F., Eichinger Ludwig, Steinert Michael, Hilbi Hubert (2018), Acanthamoeba and Dictyostelium as Cellular Models for Legionella Infection, in Frontiers in Cellular and Infection Microbiology, 8, 61.
Ribosome Levels Selectively Regulate Translation and Lineage Commitment in Human Hematopoiesis
Khajuria Rajiv K., Munschauer Mathias, Ulirsch Jacob C., Fiorini Claudia, Ludwig Leif S., McFarland Sean K., Abdulhay Nour J., Specht Harrison, Keshishian Hasmik, Mani D.R., Jovanovic Marko, Ellis Steven R., Fulco Charles P., Engreitz Jesse M., Schütz Sabina, Lian John, Gripp Karen W., Weinberg Olga K., Pinkus Geraldine S., Gehrke Lee, Regev Aviv, Lander Eric S., Gazda Hanna T., Lee Winston Y., et al. (2018), Ribosome Levels Selectively Regulate Translation and Lineage Commitment in Human Hematopoiesis, in Cell, 173(1), 90-103.e19.
Formation of the Legionella -containing vacuole: phosphoinositide conversion, GTPase modulation and ER dynamics
Steiner Bernhard, Weber Stephen, Hilbi Hubert (2018), Formation of the Legionella -containing vacuole: phosphoinositide conversion, GTPase modulation and ER dynamics, in International Journal of Medical Microbiology, 308(1), 49-57.
Structural insights into Legionella RidL-Vps29 retromer subunit interaction reveal displacement of the regulator TBC1D5
Bärlocher Kevin, Hutter Cedric A. J., Swart A. Leoni, Steiner Bernhard, Welin Amanda, Hohl Michael, Letourneur François, Seeger Markus A., Hilbi Hubert (2017), Structural insights into Legionella RidL-Vps29 retromer subunit interaction reveal displacement of the regulator TBC1D5, in Nature Communications, 8(1), 1543-1543.
Formation of the Legionella Replicative Compartment at the Crossroads of Retrograde Trafficking
Bärlocher Kevin, Welin Amanda, Hilbi Hubert (2017), Formation of the Legionella Replicative Compartment at the Crossroads of Retrograde Trafficking, in Frontiers in Cellular and Infection Microbiology, 7, 482.
ER remodeling by the large GTPase atlastin promotes vacuolar growth of Legionella pneumophila
Steiner Bernhard, Swart Anna Leoni, Welin Amanda, Weber Stephen, Personnic Nicolas, Kaech Andres, Freyre Christophe, Ziegler Urs, Klemm Robin W, Hilbi Hubert (2017), ER remodeling by the large GTPase atlastin promotes vacuolar growth of Legionella pneumophila, in EMBO reports, 18(10), 1817-1836.
Pathogen-Induced TLR4-TRIF Innate Immune Signaling in Hematopoietic Stem Cells Promotes Proliferation but Reduces Competitive Fitness
Takizawa Hitoshi, Fritsch Kristin, Kovtonyuk Larisa V., Saito Yasuyuki, Yakkala Chakradhar, Jacobs Kurt, Ahuja Akshay K., Lopes Massimo, Hausmann Annika, Hardt Wolf-Dietrich, Gomariz Álvaro, Nombela-Arrieta César, Manz Markus G. (2017), Pathogen-Induced TLR4-TRIF Innate Immune Signaling in Hematopoietic Stem Cells Promotes Proliferation but Reduces Competitive Fitness, in Cell Stem Cell, 21(2), 225-240.e5.
Reactive Oxygen Species–Producing Myeloid Cells Act as a Bone Marrow Niche for Sterile Inflammation–Induced Reactive Granulopoiesis
Zhu Haiyan, Kwak Hyun-Jeong, Liu Peng, Bajrami Besnik, Xu Yuanfu, Park Shin-Young, Nombela-Arrieta Cesar, Mondal Subhanjan, Kambara Hiroto, Yu Hongbo, Chai Li, Silberstein Leslie E., Cheng Tao, Luo Hongbo R. (2017), Reactive Oxygen Species–Producing Myeloid Cells Act as a Bone Marrow Niche for Sterile Inflammation–Induced Reactive Granulopoiesis, in The Journal of Immunology, 198(7), 2854-2864.
Type IV Secretion in Gram-Negative and Gram-Positive Bacteria
Hilbi Hubert, Nagai Hiroki, Kubori Tomoko, Roy Craig R. (2017), Type IV Secretion in Gram-Negative and Gram-Positive Bacteria, Springer International Publishing, Cham.
Quantification and three-dimensional microanatomical organization of the bone marrow
Nombela-Arrieta Cesar, Manz Markus G. (2017), Quantification and three-dimensional microanatomical organization of the bone marrow, in Blood Advances, 1(6), 407-416.
The Role of the Bone Marrow Stromal Compartment in the Hematopoietic Response to Microbial Infections
Nombela-Arrieta César, Isringhausen Stephan (2017), The Role of the Bone Marrow Stromal Compartment in the Hematopoietic Response to Microbial Infections, in Frontiers in Immunology, 7, 689.

Collaboration

Group / person Country
Types of collaboration
Prof. H. Bode/ University of Frankfurt Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. L. Eichinger/ University of Cologne Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Prof. Dr. W. Eisenreich/ TU Munich Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Dr. Jason King/ University of Sheffield Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. A. Itzen/ TU Munich Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Prof. A. Flieger/ RKI Wernigerode Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
- Exchange of personnel
Prof. D. Becher/ University of Greifswald Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Prof. C. Buchrieser/ Institute Pasteur, Paris France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Prof. B. Oppitz/ Charite University Hospital Berlin Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
- Exchange of personnel
Prof. M. Seeger/ University of Zürich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Prof. P. Cosson/ University of Geneva Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Prof. C. Hedberg/ Umea University Sweden (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Dr. R. Kammerer/ Paul-Scherrer Institute Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Dr. François Letourneur/ University of Montpellier France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. A. Haas/ University of Bonn Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
PD Dr. A. Müller-Taubenberger/ LMU Munich Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Dr. M. Bonazzi/ University of Montpellier France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. T. Soldati/ University of Geneva Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Awards

Title Year
Fellow, American Academy of Microbiology 2018

Associated projects

Number Title Start Funding scheme
153200 Formation of the Legionella-containing vacuole: Effectors targeting retrograde trafficking and microtubules 01.01.2015 Project funding (Div. I-III)
159597 Multidimensional analysis of the dynamics of bone marrow microenvironment during inflammation 01.04.2015 Project funding (Div. I-III)
146295 Circumvention of Host Innate Immune Defenses by Bacterial Nucleases 01.07.2013 Project funding (Div. I-III)
175557 Virulence and communication of Legionella: Molecular determinants of pathogen-host cell interactions 01.04.2018 Project funding (Div. I-III)
153349 Tuberculosis - Protein Secretion, modification, Drug and Vaccine Development (TB-PSDVD) 01.04.2014 Project funding (Div. I-III)
166571 Exploring the interface between ribosome assembly and nucleocytoplasmic transport 01.10.2016 Project funding (Div. I-III)
176252 Staphylococcus aureus - persisting bacteria that are difficult to eradicate 01.10.2017 Project funding (Div. I-III)

Abstract

Life science research at the University of Zurich (UZH) and University Hospital Zurich (USZ) has a very broad scope. Of major importance are cellular and molecular aspects of various biological systems. Imaging is key to many of these research topics. Over the last years a number of new microscopy techniques (e.g. super resolution microscopy or selective plane illumination microscopy) have evolved that allow new approaches of fluorescent imaging of individual cells, tissue and whole organisms. However, classical 3D microscopy employing a confocal laser scanning microscope (CLSM) is still one of the most frequently and widely used approaches. New developments have made this well-established technique even more powerful: novel detectors allow for faster imaging with decreased phototoxicity at improved resolution. We would like to offer such a new CLSM for the life science research community at the University of Zurich and the University Hospital of Zurich. To this end, we propose to purchase an advanced, state-of-the-art CLSM and install it in the framework of the Center for Microscopy and Image Analysis (ZMB) at the Institute of Medical Microbiology, located at the city campus of the UZH/USZ.
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