Project

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New electronics for 900MHz NMR spectrometer

Applicant Wider Gerhard
Number 139221
Funding scheme R'EQUIP
Research institution Institut für Molekularbiologie und Biophysik ETH Zürich
Institution of higher education ETH Zurich - ETHZ
Main discipline Biophysics
Start/End 01.12.2011 - 30.11.2012
Approved amount 350'000.00
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All Disciplines (2)

Discipline
Biophysics
Molecular Biology

Lay Summary (English)

Lead
Lay summary

Nuclear magnetic resonance (NMR) in solution is an established technique in physics, chemistry and biology; in the latter discipline it has an especially large impact in structural biology. Numerous studies of three-dimensional structures of macromolecules and their dynamic features as well as investigations of their interactions have demonstrated the significance of NMR for biological research. This proposal contributes funds for the replacement of outdated electronics of a 900 MHz NMR instrument. With the upgrade the instrument belongs again to the top range of NMR spectrometers world-wide and the reliability and versatility will be much improved in the interest of its users. Measurements on the 900 MHz NMR instrument support research in a wide range of topics which include but are not limited to studies of membrane proteins involved in the communication between cells and their environment; studies of multi-domain RNA-binding proteins involved in protein-engineering and protein regulation and studies of their interaction with RNA; studies of Amyloid proteins associated with neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease; studies of post-transcriptional regulation of germ cell apoptosis in C. elegans; the development of new methods in NMR spectroscopy; studies of structural and dynamic aspects of proteins in the ubiquitination pathway, studies of protein-RNA complexes involved in alternative splicing which multiplies the information of genes; studies of the structure and function of glycans and the elucidation of a "Glycocode"; …. . Many more research topics will be added during the life-time of the new electronics for the 900 MHz NMR instrument. In summary, the structural and dynamic studies of biological macromolecules and their interaction partners with the upgraded 900 MHz NMR spectrometer will result in a detailed physical understanding of the properties, the functions, and the interactions of the investigated molecules, which is a basis for further biological, medical and pharmaceutical research.

Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Publications

Publication
Automated projection spectroscopy (APSY) for the assignment of NMR resonances of biological macromolecules.
Krähenbühl Barbara, Wider Gerhard (2012), Automated projection spectroscopy (APSY) for the assignment of NMR resonances of biological macromolecules., in Chimia, 66(10), 770-4.
Plasticity of the β-trefoil protein fold in the recognition and control of invertebrate predators and parasites by a fungal defence system.
Schubert Mario, Bleuler-Martinez Silvia, Butschi Alex, Wälti Martin A, Egloff Pascal, Stutz Katrin, Yan Shi, Collot Mayeul, Mallet Jean-Maurice, Wilson Iain B H, Hengartner Michael O, Aebi Markus, Allain Frédéric H-T, Künzler Markus (2012), Plasticity of the β-trefoil protein fold in the recognition and control of invertebrate predators and parasites by a fungal defence system., in PLoS pathogens, 8(5), 1002706-1002706.
Solution structure of the N-terminal dsRBD of Drosophila ADAR and interaction studies with RNA.
Barraud Pierre, Heale Bret S E, O'Connell Mary A, Allain Frédéric H-T (2012), Solution structure of the N-terminal dsRBD of Drosophila ADAR and interaction studies with RNA., in Biochimie, 94(7), 1499-509.
Structural basis for sigma factor mimicry in the general stress response of Alphaproteobacteria
Campagne S. Damberger F.F. Kaczmarczyk A. Francez-Charlot A. Allain F.H. Vorholt J.A. (2012), Structural basis for sigma factor mimicry in the general stress response of Alphaproteobacteria, in Proc. Natl. Acad. Sci. USA, 109(21), 1405.
Automated Projection Spectroscopy and Its Applications
Hiller S. and Wider G. (2012), Automated Projection Spectroscopy and Its Applications, in Curr. Chem. , 316, 21.
A syn-anti conformational difference allows SRSF2 to recognize guanines and cytosines equally well.
Daubner Gerrit M, Cléry Antoine, Jayne Sandrine, Stevenin James, Allain Frédéric H-T (2012), A syn-anti conformational difference allows SRSF2 to recognize guanines and cytosines equally well., in The EMBO journal, 31(1), 162-74.
Cotranslational structure acquisition of nascent polypeptides monitored by NMR spectroscopy
Eichmann C Preissler S Riek R Deuerling E. (2011), Cotranslational structure acquisition of nascent polypeptides monitored by NMR spectroscopy, in Proc Natl Acad Sci U S A, 107, 9111.
Structural basis of pre-let-7 miRNA recognition by the zinc knuckles of pluripotency factor Lin28
Loughlin F.E. Gebert L.F. Towbin H. Brunschweiger A. Hall J. Allain F.H. (2011), Structural basis of pre-let-7 miRNA recognition by the zinc knuckles of pluripotency factor Lin28, in Nat. Struct. Mol. Biol., 19(1), 84.

Collaboration

Group / person Country
Types of collaboration
Prof. J. Vorholt/ETH-Z Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Prof. A. Krainer/CSHL United States of America (North America)
- Publication
Prof. G. Schertler and Dr. V. Dmitry/PSI Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. E. Weber-Ban/ETH-Z Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. M. Aebi/ETH-Z Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. J. Hall/ETHZ Switzerland (Europe)
- Publication
Prof. S. Choe/Salk Institute United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. M. Jantsch/Univ. Vienna Austria (Europe)
- Publication
Prof. M. Hengartner and Dr. I. Jelezarov/Univ. Zürich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Prof. R. Sigel/Univ. Zürich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. H. Simon/Univ. Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Dr. S. Ravindranathan/NCL Pune India (Asia)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Drs. N. Meisner and J. Hunziker/Novartis Basel Switzerland (Europe)
- Industry/business/other use-inspired collaboration
Prof. M. Peter/ETH-Z Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. V. Panse/ETHZ Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Exchange of personnel
Prof. R. Emeson/Univ. Vanderbilt United States of America (North America)
- Publication
Prof. H. Stahlberg/Univ. Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. D. Eisenberg/UCLA United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
Prof. E. Deuerling/Univ. Konstanz Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. B. Chabot/Sherbrook Canada (North America)
- Publication
Prof. D. Black/UCLA United States of America (North America)
- Publication
Prof. B. Ernst/Univ. Basel) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Cell symposia “functional RNA” 02.12.2012 Sitges, Spain
FEBS meeting 2012 04.09.2012 Seville, Spain
NCCR symposium 29.08.2012 Zurich, Switzerland
XXVth ICMRBS 26.07.2012 Lyon, France
Intedisciplinary research in molecular biology and biomedecin 28.03.2012 Warsaw, Poland
Indo Swiss NMR symposium 23.01.2012 NCL, Pune, Indien
Indian Biophysical Society Meeting 19.01.2012 University of Madras, Chennai, Indien
Satellite Meeting of Euromar 19.08.2011 Bad Homburg, Germany


Associated projects

Number Title Start Funding scheme
127454 Post-transcriptional regulation of germ cell apoptosis in C. elegans 01.11.2009 Sinergia
133134 NMR structure determination of protein-RNA complexes involved in pre-mRNA editing and translation regulation 01.10.2010 Project funding
120048 Technische Entwicklunen in biomolekularer NMR Spektroskopie 01.06.2009 Project funding
144242 Combined use of NMR and DNA encoded libraries for drug discovery 01.12.2012 Project funding
126488 Structural Studies of Aggregates and Membrane Proteins 01.01.2010 Project funding
131031 Nuclear import and substrate recognition by double stranded RNA binding domains (D-A-CH/LAE) 01.05.2010 Project funding
127333 Glycocode: towards the structure and function of glycans 01.11.2009 Sinergia

Abstract

In the mid 1970's the Institute of Molecular Biology and Biophysics installed a high field NMR laboratory on the initiative of Prof. K. Wüthrich. Due to continuous financial support by private, industrial and public funding the NMR lab could be maintained at the edge of technical developments and the number of hosted NMR spectrometers was gradually increased from one 360 MHz instrument to currently six instruments in the range of 400 to 900 MHz. Since 1995 Prof. Gerhard Wider is the head of the NMR facility and it is in this capacity that he functions as responsible applicant for this application.In this funding application we request new electronics for the 900 MHz NMR spectrometer which was purchased in 2000 and installed in early 2002. The term "electronics" includes all hardware required to operate the instrument except the magnet and the CryoProbe (CryoProbe: trademark of the company Bruker). The superconducting magnets used for NMR spectrometers are not subject to regular wear and tear and can often be operated for 20 and more years. Our 900 MHz magnet is fully functional and fulfills the same specifications as at the time of installation. The CryoProbe is used to detect the NMR signal and in our case was purchased only 2 years ago; this CryoProbe can normally be operated at least another 5 years. All other parts of the 900 MHz spectrometer electronics are in operation since the time of installation. The costs for the new electronics amount to about 10% of the total investment price for a 900 MHz NMR spectrometer that is configured as the existing machine. In the last ten years there were major advances in NMR technology. Modern NMR electronics is more digitized and more miniaturized with the concomitant advantages, e.g. in stability, linearity, dynamic range, reliability and purity of radio-frequencies. One consequence is that the existing CryoProbe will produce a higher sensitivity with the new electronics than on the current system. The technical developments have reached a stage where we can no longer install the newest software on our system. Thus, we are cut-off from all developments even if our system would in principle allow performing some of the new software features. Our NMR spectrometers are operated 24h a day and seven days a week. Thus, at the time of a possible replacement the 900 MHz electronics will have been continuously operated for more than ten years. The signal detected by NMR instruments is very weak and requires the whole instrument to be in top condition for optimal results. So far, obvious failures and malfunctioning of the 900 MHz electronics have increased only slightly, however, this situation can deteriorate any time. One measurement may take up to three days and one little glitch in the electronics can severely impair or even destroy the whole measurement. Since the life time of the measured samples may be very limited, one failed experiment can produce considerable loss in time and may require substantial additional financial resources. Last year the NMR lab of the Institute of Molecular Biology and Biophysics has become a tech-nology platform of the Biology Department of the ETH which increased the number of potential users substantially. Currently, on the 900 MHz spectrometers the co-applicants Prof. Frederic Allain and Prof. Roland Riek (D-CHAB) are still the main users. The 900 MHz NMR spectrometer at the ETH is the instrument with the highest magnetic field and the highest sensitivity in Switzerland and is also used by researchers from outside the ETH. In summary, the purchase of new electronics for the 900 MHz spectrometer at the ETH is absolutely essential for the continuation of a competitive research at the forefront of NMR spectroscopy applied to structural biology.
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