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Cryo-Electron Microscopy in the ZMB of the University of Basel

Applicant Stahlberg Henning
Number 164074
Funding scheme R'EQUIP
Research institution C-CINA Biozentrum Universität Basel
Institution of higher education University of Basel - BS
Main discipline Cellular Biology, Cytology
Start/End 01.06.2016 - 31.05.2017
Approved amount 405'000.00
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All Disciplines (7)

Discipline
Cellular Biology, Cytology
Experimental Microbiology
Biochemistry
Molecular Biology
Structural Research
Biophysics
Medical Microbiology

Keywords (5)

Single particle cryo-EM; Electron Microscopy; 3D imaging; Structural Biology; Cryo-TEM

Lay Summary (German)

Lead
Mit diesem Antrag erbitten wir finanzielle Unterstützung zur Anschaffung eines Elektronenmikroskops für die Untersuchungen von tief-gefrorenen biologischen Proben in der Elektronenmikroskopie Service Facility "BioEM Lab" der Universität Basel.
Lay summary

Das BioEM Lab wurde in Frühjahr 2016 als Nachfolger des Zentrum für Mikroskopie (ZMB) der Uni Basel gegründet.  Das BioEM Lab bietet seinen Kunden moderne Elektronenmikroskopie Strukturuntersuchungen als Service an. Hierzu gehört unter anderem auch die hoch-auflösende Strukturbestimmung von einzelnen Protein Partikeln, welche im tief-gefrorenen Kryo-Zustand (-190 ºC) mit dem beantragten Elektronenmikroskop fotografiert werden sollen. Durch Computer Bildverarbeitung wird anschliessend die detaillierte 3D Struktur bis hin zu atomarer Auflösung ermittelt.

Das ZMB hat bisher diese moderne Methode des "Cryo-EM" nicht anboten. Mit Inbetriebnahme des hier beantragten neuen Gerätes kann das BioEM Lab als Nachfolger des ZMB nun auch diese revolutionäre Methode anbieten.

Die Kunden des BioEM Labs sind vorwiegend aus dem Life Sciences Bereich, und schliessen Forschergruppen des Biozentrums der Uni Basel, sowie aus dem weiteren Raum Basel, Schweiz, und benachbartes Ausland mit ein. 

Mit dem Gerät werden somit zum Beispiel bakterielle Proteine untersucht, um zu verstehen, wie manche gefährlichen Erreger die menschlichen Wirtszellen manipulieren um zu chronischen Infektionen zu führen. Ein Verständnis dieses Mechanismus ist nötig, um gezielte Behandlungsstrategien entwickeln zu können. Andere Beispiele von untersuchten Proben stammen aus der Erforschung der Parkinson'schen Krankheit, oder aus der Nano-Biologie.

 

Direct link to Lay Summary Last update: 15.08.2016

Responsible applicant and co-applicants

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159525 Molecular mechanisms of force generation and protein translocation by contractile tails 01.02.2016 Project funding (Div. I-III)
177084 Efficient cryo electron microscopy of macromolecular assemblies and membrane proteins 01.09.2018 R'EQUIP
155778 Dynamics of the bacterial Type VI secretion system assembly and substrate delivery 01.09.2015 SNSF Starting Grants
159696 Multienzymes in Lipid and Polyketide Biosynthesis 01.04.2015 Project funding (Div. I-III)
146929 Electron Microscopy of Membrane Proteins 01.04.2013 Project funding (Div. I-III)
146614 Reconciling Molecular and Transport Aspects of Nuclear Pore Complex Functionality: Karyopherin Binding Avidity, FG Domain Conformation and the Role of RanGTP Revisited 01.06.2013 Project funding (Div. I-III)

Abstract

We here request financial support for the acquisition of an efficient automated 200kV cryo-transmission electron microscope (cryo-TEM) for screening and cellular scale analysis. This instrument is intended for the ZMB, the “Zentrum für Mikroskopie Basel”, which is the Electron Microscopy (EM) service facility of the University Basel. The ZMB so far did not offer cryo-TEM investigations in its portfolio. The ZMB has now been transformed into the BioEM Lab, which with the installation of the requested instrument now offers cryo-EM as service also.Various laboratories at the University of Basel and beyond would benefit from the availability of cryo-TEM in the service institution. The suggested workhorse cryo-EM instrument is fully suited for analysis at the cellular level with 1nm resolution. It uniquely supports the time-consuming sample optimization for high-resolution single particle structure determination by cryo-TEM. Once, optimized samples are ready for cryo-TEM, high-resolution data could then be acquired with little time efforts else-where, as for example in the C-CINA of the Biozentrum of the University of Basel, or in other cities (e.g., ScopeM at the ETH Zurich, or the NECEN facility in Leiden in The Netherlands). The availability of an efficient screening microscope would also further reinforce a highly focused use of high-end microscopes and in this regard serve many Swiss scientist requiring access to high-end instruments.Cryo-TEM will also be highly valuable for many laboratories at the University of Basel to characterize liposome preparations, synthetic life constructs (the NCCR Molecular Systems Engineering in Basel will implement three new research groups in this direction), or synthetic molecule structures such as block-polymer membranes (Wolfgang Meier, Chemistry). For these type of projects, the proposed 200kV cryo-TEM instrument is an ideal choice. The proposed cryo-TEM instrument should be an automated or an automatizable 200kV TEM, preferentially a system-in-a-box such as the FEI Talos, alternatively an automizable JEOL JEM-2100F. Two ZMB employees are already trained in cryo-TEM. A suitable location in the ZMB is available for the new instrument. Maintenance will be provided by an available EM service engineer, employed at the University of Basel. Sufficient consumable support funds are secured. We here present a several immediate applications for cryo-TEM at the ZMB/BioEM Lab. A large number of additional customers will also benefit from the proposed instrument, as described in chapter 3.
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