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Purchase of a 900 MHz High-Resolution NMR Instrument

Research Project
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01.12.2013
 - 30.11.2014

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.

Funding

PURCHASE OF A 900 MHZ HIGH-RESOLUTION NMR INSTRUMENT

SNF Projekt (GrantsTool), 12.2013-11.2014 (12)
PI : Grzesiek, Stephan.
CI : Hiller, Sebastian,Jenal, Urs,Maier, Timm,Schirmer, Tilman.

Members (5)

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Stephan Grzesiek

Principal Investigator
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Sebastian Hiller

Co-Investigator
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Urs Jenal

Co-Investigator
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Timm Maier

Co-Investigator
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Tilman Schirmer

Co-Investigator