Project

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Serial block face SEM

Applicant Zuber Benoît
Number 150823
Funding scheme R'EQUIP
Research institution Institut für Anatomie Universität Bern
Institution of higher education University of Berne - BE
Main discipline Structural Research
Start/End 01.12.2013 - 30.11.2014
Approved amount 428'575.00
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All Disciplines (2)

Discipline
Structural Research
Cardiovascular Research

Keywords (4)

three-dimension; electron microscopy; imaging; ultrastructure

Lay Summary (German)

Lead
Um die Erforschung der Funktion der Lebewesen zu erleichtern, kann deren feine Struktur mittels Elektronenmikroskopie detailliert untersucht werden. Mit den konventionellen Methoden können nur sehr kleine Probenvolumen analysiert werden. Eine neue Technologie ermöglicht die Untersuchung von viel grösseren Mengen, die zu einer besseren Darstellung und Erkennung der dreidimensionalen, funktionellen Struktur der Lebewesen führt.
Lay summary

Ziele:

Diese neue, elektronenmikroskopische Vorgehensweise automatisiert nicht nur das Zuschneiden von Proben, sondern auch die Aufnahme von Bildern. Dies führt zu einer enormen Beschleunigung dieser beiden Prozesse. Mit der Unterstützung des Schweizerischen Nationalfonds werden wir ein entsprechendes mikroskopisches Gerät erwerben und dieses für verschiedenste Forschungszwecke einsetzen. Über 20 Forschungsgruppen haben ihre Projekte bereits geplant und sind für deren Durchführung zwingend auf dieses Gerät angewiesen. Diese Projektgruppen arbeiten an verschiedenen Universitäten in Bern, Freiburg, Zürich, Lausanne, Basel und an der ETH Lausanne. Die Projektarbeiten konzentrieren sich hauptsächlich auf die Biologie von Herz oder Lunge, der Neurobiologie sowie diversen Aspekte der Blut- und Lymphgefässe.

 

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts:

Ein Teil der durchgeführten Arbeiten widmet sich der Grundlagenforschung. Ein anderer Teil konzentriert sich auf die angewandte Forschung mit Schwergewicht in der Entwicklung von Therapien gegen Krebs und Herz-Kreislauferkrankungen und neuer Untersuchungsverfahren im forensischen Bereich der Rechtsmedizin.

Direct link to Lay Summary Last update: 06.12.2013

Lay Summary (French)

Lead
L'étude de la structure des êtres vivants à une échelle sub-microscopique, typiquement à l'aide du microscope électronique, permet de mieux comprendre leur fonctionnement. Avec les méthodes traditionnelles, seuls de très petits volumes d'échantillon peuvent être analysés. Une nouvelle technologie permet d'étudier de nettement plus grands volumes, ce qui devrait mener à une bien meilleure compréhension de l'arrangement tridimensionnel détaillé des êtres vivants.
Lay summary

Objectifs:

Cette nouvelle approche de microscopie électronique se base sur l'automatisation non seulement de la coupe de l'échantillon mais aussi de l'acquisition d'images, ce qui conduit à une énorme accélération de ces deux processus.

Avec le soutien du Fonds National nous allons acquérir une telle machine. Les objectifs visés sont multiples. Plus de 20 groupes de recherche ont formulés des projets qui vont bénéficier du nouvel équipement. Ces groupes sont basés principalement à l'université de Berne mais également à l'université de Fribourg, l'université de Zurich, l'université de Lausanne, l'université de Bâle, et l'école polytechnique fédérale de Lausanne. Plusieurs projets sont centrés sur la biologie du cœur, sur celle des poumons, sur la neurobiologie, ainsi que sur divers aspects des vaisseaux sanguins et lymphatiques.

 

Contexte scientifique et sociétal du projet:

Une partie des recherches effectuées sur le nouvel appareillage sera d'ordre fondamental alors qu'une autre partie sera orientée sur la pratique, notamment dans le cadre du développement de thérapies contre le cancer et les maladies cardiovasculaires, ainsi que dans le cadre du diagnostic post mortem.

 

Direct link to Lay Summary Last update: 06.12.2013

Responsible applicant and co-applicants

Publications

Publication
Impaired mTORC1-Dependent Expression of Homer-3 Influences SCA1 Pathophysiology
Ruegsegger Celine, Stucki David M., Steiner Silvio, Angliker Nico, Radecke Julika, Keller Eva, Zuber Benoit, Ruegg Markus A., Saxena Smita (2016), Impaired mTORC1-Dependent Expression of Homer-3 Influences SCA1 Pathophysiology, in NEURON, 89(1), 129-146.
Mitochondrial impairments contribute to Spinocerebellar ataxia type 1 progression and can be ameliorated by the mitochondria-targeted antioxidant MitoQ
Stucki David M., Ruegsegger Celine, Steiner Silvio, Radecke Julika, Murphy Michael P., Zuber Benoit (2016), Mitochondrial impairments contribute to Spinocerebellar ataxia type 1 progression and can be ameliorated by the mitochondria-targeted antioxidant MitoQ, in FREE RADICAL BIOLOGY AND MEDICINE, 97, 427-440.
High resolution microscopy reveals an unusual architecture of the Plasmodium berghei endoplasmic reticulum
Keiser Gesine, De Niz Mariana, Zuber Benoît, Burda Paul-Christian, Kornmann Benoît, Heussler Volker T., Stanway Rebecca R., High resolution microscopy reveals an unusual architecture of the Plasmodium berghei endoplasmic reticulum, in Molecular Microbiology, Epub ahead of print(-), 1.

Collaboration

Group / person Country
Types of collaboration
Microscopy Imaging Centre Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
- Industry/business/other use-inspired collaboration

Associated projects

Number Title Start Funding scheme
175953 How does the 3-dimensional structure of the pulmonary acinus develop, regenerate, and change during breathing? What are the functional consequences for ventilation and particle deposition? 01.10.2017 Project funding (Div. I-III)
139098 Time-resolved structural study of calcium-dependent membrane fusion 01.07.2012 SNSF Professorships
146215 Molecular mechanisms of extracellular DNA trap formation by granulocytes 01.04.2013 Project funding (Div. I-III)
185536 Microglial activation in Complement C4-stratified schizophrenic patients and in a mouse model of C4 overexpression (NEURON-119 microSCHIZ) 01.01.2020 ERA-NET NEURON
121980 The molecular mechanisms of ceramide action in apoptosis 01.10.2008 Project funding (Div. I-III)
128415 Dendritic excitability and synaptic plasticity of cortical neurons under physiological and pathological conditions of neuropathic pain 01.07.2010 SNSF Professorships
140931 Transcription factors FOXC2 and PROX1 in lymphatic vascular development and cancer 01.07.2012 SNSF Professorships
133092 Defining the specific role of endothelial-expressed Ig-superfamily cell adhesion molecules (IgCAMs) in mediating the individual steps involved in T cell extravasation across the blood-brain barrier in vitro and in vivo 01.10.2010 Project funding (Div. I-III)
138297 Structural and Electrical Remodeling of Cardiac Tissue: Consequences for Impulse Generation and Propagation at the Cellular Network Level. 01.10.2011 Project funding (Div. I-III)
135550 In-vivo study of lung physiology with sub-second X-ray tomographic microscopy 01.05.2011 Interdisciplinary projects
140691 Pathogen-host cell interactions during the liver stage of Plasmodium parasites 01.08.2012 Project funding (Div. I-III)
135535 Force-controlled patch clamp (pc-FluidFM) 01.04.2011 Interdisciplinary projects
141811 Cell-cell communication and mechano-transduction in lymphatic vascular morphogenesis and disease 01.09.2012 Sinergia
143766 Artificial mesenchymal progenitor cell niches for bone tissue engineering 01.11.2012 Interdisciplinary projects
135740 Regulatory mechanisms of intussusceptive (splitting) angiogenesis and their potential clinical implications 01.12.2011 Project funding (Div. I-III)
130680 Knock-out mice for the calcium-binding proteins parvalbumin, calbindin D-28k and calretinin. Models for muscle and brain diseases. 01.05.2010 Project funding (Div. I-III)
147060 Molecular Determinants of Nav1.5 Multiprotein Complexes in Cardiac Cells 01.04.2013 Project funding (Div. I-III)
144167 Angiogenesis in skeletal muscle induced by endurance exercise 01.10.2012 Project funding (Div. I-III)
135596 Is Fetal and Placental Size, Blood Pressure and Overall Pregnancy Outcome Determined by Aldosterone Production and Salt Intake? 01.09.2011 Project funding (Div. I-III)
141127 Alveolar-capillary microfluidic model for the analysis of lung injury, regeneration and repair 01.05.2012 Project funding (Div. I-III)
143898 Cellular and molecular mechanisms of vascular maturation for therapeutic angiogenesis 01.10.2012 Project funding (Div. I-III)

Abstract

Transmission electron microscopy (TEM) of ultrathin tissue sections has played a critical role in our understanding of cell and tissue structure and function. Most of the images gathered with this technique are two-dimensional (2D) and have provided a wealth of information. Nev-ertheless three-dimensional (3D) images are required to tackle a number of biological problems. Over the past 10 years, electron tomography has become a widely used 3D TEM method involv-ing automatic data collection and semi-automatic three-dimensional reconstruction. High-resolution 3D data can be obtained within less than an hour. Nonetheless the volume that can be analysed with this technique is limited to the thickness of the ultrathin section (typically lower than 300 nm), which is still much too small to address many issues. On the other hand, serial section TEM has been used since the early days of electron microscopy (EM) to recon-struct larger volumes albeit at lower resolution. The main drawback of this technique lies nonetheless in its technical difficulty and in its low throughput, which limits the sample thick-ness that can be practically analysed to a few micrometres in most cases.Quite recently, serial block face scanning electron microscopy (SBF-SEM) has emerged as a powerful technique to obtain 3D reconstructions of large biological samples. The latter are de-hydrated, heavy metal stained and resin embedded similarly as for TEM but the whole resin block, as opposed to ultrathin sections, is inserted in the microscope. The microscope is equipped with an internal ultramicrotome. After acquiring an image of the sample surface, which appears quite similar to a TEM image, an ultrathin section is removed from the sample and an image of the newly exposed surface is obtained. This process is fully automatic and can be repeated hundreds of times overnight or many thousands of times over longer period of time, leading to reconstructions of several hundred micrometre thickness.The Institute of Anatomy has nearly 50 years' experience in electron microscopy. The Institute and the applicants, who have pioneered several advanced EM and 3D X-ray imaging modalities, would like to acquire an SBF-SEM device in order to stay at the forefront of ultrastructural research. 22 research projects, of which 15 originate from groups external to the Institute of Anatomy, will directly benefit from this new technology. Moreover, this should prove very valu-able to members of other academic centres of Switzerland (see projects and support letters) as well as to members of the Industry since the Institute of Anatomy provides service to external researchers.
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