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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 This proposal contributes funds for the replacement of outdated electronics of a 900 MHz NMR instrument.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.

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Last update: 21.02.2013

Active participation

Number	Title	Start	Funding scheme

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.