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Purchase of a 900 MHz high-resolution NMR instrument

English title Purchase of a 900 MHz high-resolution NMR instrument
Applicant Grzesiek Stephan
Number 150814
Funding scheme R'EQUIP
Research institution Abteilung Strukturbiologie und Biophysik Biozentrum Universität Basel
Institution of higher education University of Basel - BS
Main discipline Biophysics
Start/End 01.12.2013 - 30.11.2014
Approved amount 600'000.00
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Keywords (10)

protein; metabolism; membrane proteins; bacterial virulence; cancer; protein interaction; dynamics; structure; protein folding; GPCR

Lay Summary (German)

Lead
Kernspinresonanz (Nuclear Magnetic Resonance, NMR) ist die einzige experimentelle Methode, mit der Struktur und Dynamik von Biomolekülen und ihrer Wechselwirkungen in atomarer Auflösung unter quasinatürlichen Bedingungen untersucht werden können. Dies ist notwendig, um die biologische Funktion zu verstehen und in weiteren Ansätzen z. B. durch Medikamente zu beeinflussen.
Lay summary

Das Biozentrum der Universität Basel betreibt zur Zeit ein 800 MHz NMR Gerät, das von mehreren Gruppen benutzt wird. Mit dem Bau des neuen Biozentrums wird es möglich, ein 900 MHz NMR Gerät anzuschaffen, welches durch höhere Auflösung und Empfindlichkeit die wissenschaftlichen Möglichkeiten am Biozentrum erheblich erweitern und die internationale Konkurrenzfähigkeit sichern wird. Als zukünftige Anwendung sind vorgesehen A) die Untersuchung krankheitsrelevanter Protein in Krebs und HIV, sowie die Weiterentwicklung von NMR-Methoden (Gruppe Grzesiek); B) die Charakterisierung von Funktion und Faltung grosser Biomoleküle mit Schwerpunkt integrale Membranproteine (Gruppe Hiller); C) die Untersuchung  von Proteinen, Wechselwirkung und Funktion in der Signaltransduktion durch c-di-GMP (Gruppen Schirmer, Jenal); D) die Untersuchung grosser Proteinkomplexe (Gruppen Maier, Hiller).

Weitere Anwendung sind durch die Gruppen Ernst, Hamburger (Departement für Pharmazeutische Wissenschaften, Universität Basel), Ward, Häussinger (Dept. Chemie, Universität Basel), Schertler (Paul-Scherrer-Institut, Villigen), Bühler (Friedrich-Miescher-Institut, Basel), Bumann (Biozentrum, Universität Basel) geplant.

 

Der eingereichte Antrag an den Schweizer Nationalfonds bezieht sich auf eine Teilfinanzierung von 800'000 CHF der Gesamtanschaffungsumme von 5'150'000 CHF des 900 MHz Gerätes. Der Rest der Finanzierung erfolgt durch die Universität Basel.

Direct link to Lay Summary Last update: 18.06.2014

Responsible applicant and co-applicants

Publications

Publication
Cyclic di-GMP acts as a cell cycle oscillator to drive chromosome replication.
Lori C, Ozaki S, Steiner S, Böhm R, Abel S, Dubey B N, Schirmer T, Hiller S, Jenal U (2015), Cyclic di-GMP acts as a cell cycle oscillator to drive chromosome replication., in Nature, advance online publication(0), 0-0.
An economic approach to efficient isotope labeling in insect cells using homemade 15N-, 13C- and 2H-labeled yeast extracts
Opitz Christian, Isogai Shin, Grzesiek Stephan, An economic approach to efficient isotope labeling in insect cells using homemade 15N-, 13C- and 2H-labeled yeast extracts, in Journal of Biomolecular NMR, in press(in press), 0-0.

Collaboration

Group / person Country
Types of collaboration
Prof. Thomas Ward, University of Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Prof. Urs Jenal, Biozentrum, University of Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Prof. Beat Ernst, University of Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Prof. Tilman Schirmer, Biozentrum, University of Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Prof. Gebhard Schertler/Paul Scherrer Institut Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Dr. W Jahnke/Novartis Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Dirk Bumann, Biozentrum, University of Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Prof. U. Zaehringer/FZ Borstel Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Associated projects

Number Title Start Funding scheme
138414 Molecular mechanisms of c-di-GMP signaling and of target AMPylation 01.02.2012 Project funding (Div. I-III)
127433 Mechanisms of cyclic di-GMP signaling 01.02.2010 Sinergia
128419 Structure, Function and Folding of Membrane Proteins and their Complexes 01.08.2010 SNSF Professorships
141898 NMR studies of GPCRs: Structure, dynamics and interactions with ligands and signaling proteins 01.12.2012 Sinergia
132857 Biomacromolecular structures, dynamics and interactions by NMR and new developments in NMR technology 01.10.2010 Project funding (Div. I-III)
147090 Cyclic di-GMP signaling in cell behavior and reproduction 01.04.2013 Project funding (Div. I-III)
149927 Biomacromolecular structures, dynamics and interactions by NMR and new developments in NMR technology 01.10.2013 Project funding (Div. I-III)
138262 Multienzymes and the Regulation of Eukaryotic Lipid Metabolism 01.01.2012 Project funding (Div. I-III)

Abstract

Background - Biological function results from time-dependent interactions between biomolecules. It is ultimately encoded in the primary chemical structures of molecules, which determine the positions and movements of their atoms in space. NMR spectroscopy is the only experimental method, which yields both structural and dynamical information on biomolecules at atomic resolution with minimal invasiveness and at close to natural conditions. As such, it can provide unique information to understand the connection between chemical structure, three-dimensional structure, dynamics and ultimately function.The application of NMR spectroscopy to large interesting biomolecular systems is limited by sensitivity and resolution, both of which increase strongly with magnetic field strength. The planned new building for the Biozentrum of the University Basel provides the unique opportunity to upgrade the present 800 MHz NMR instrument to a state-of-the-art 900 MHz instrument. This will substantially improve the scientific capacities of the Biozentrum’s high-field NMR center. The new installation will benefit from the strong technical and biological expertise of the principal applicants and the high demand for NMR characterization of exciting biological projects inside and outside of the University of Basel.Research proposal - Expertise, maintenance, running, building and a large part of the total purchase costs will be provided by the Biozentrum and the University of Basel. The core users will use the instrument to A) study structures and interactions of disease-relevant biomolecules and to further develop high-resolution NMR methods (Grzesiek, principal applicant); B) characterize structure, function and folding mechanisms of large biomacromolecules and their complexes with a focus on integral membrane proteins (Hiller); C) investigate proteins, interaction and functional mechanisms in cyclic-di-GMP signaling (Schirmer, Jenal); D) study large protein complexes (Maier, Hiller). Further research projects comprise 1) interactions of the uropathogenic E. coli protein FimH with glycoproteins from the urothelial cell surface (Ernst); 2) interactions of bioactive natural products with target proteins (Hamburger); 3) the catalytic activity of artificial metalloenzymes (Ward, Häussinger); 4) dynamics and interaction of G-protein coupled receptors (Schertler); 5) interactions and dynamics of histone-binding proteins and their role in heterochromatin silencing (Bühler); 6) alterations in cellular metabolism of eukaryotic cells upon infection with pathogens (Bumann).Expected value - Structures and motions of biomolecules need to be determined at atomic resolution to understand their mechanisms from first principles. This information can be provided by NMR analysis. This is a fundamental prerequisite to unravel the connection between biomolecular structure, dynamics and function, as well as for the rational intervention into biological processes such as drug design. Justification of the needed equipment - The new instrument will provide significant increases in sensitivity and resolution for the NMR analysis of structures and motions of biomolecules. The reduced required concentrations and the larger achievable molecular sizes will further extend its applicability to highly challenging biomolecular systems. The instrument will satisfy the high demand for such NMR characterizations within the University of Basel and from outside collaborations. The foreseen research projects comprise several medically relevant G-protein coupled receptors (GPCRs), cancer drug targets, pathogenic bacterial systems, large molecular machines such as membrane protein assembly and polypeptide translocation complexes, as well as general questions of protein folding. The new instrument will ensure that this research can be carried out at an internationally competitive level.
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