NMR spectrometer of superlatives

One of the world´s three most powerful high-resolution 1.2 GHz NMR spectrometers comes to Göttingen

July 22, 2020

It looks like a giant thermos flask and weighs eight tons. But that is not the only reason the new 1.2 Gigahertz nuclear magnetic resonance spectrometer is a worldwide research heavyweight. With its magnetic field strength, the technology sets new standards in high resolution nuclear magnetic resonance (NMR) spectroscopy: 28.2 Tesla – almost 600,000 times stronger than the earth´s magnetic field. Presently, there are only three of these high-tech instruments; besides the University of Florence and ETH Zurich there is now one set up in Göttingen at the Max Planck Institute for Biophysical Chemistry. The costs for the instrument are 12.5 million euros.

A 60-ton crane and two trucks were necessary to put the new NMR spectrometer safely into the recently built hall at the institute. In the future, this innovative technology, now in Göttingen through the efforts of Christian Griesinger and Markus Zweckstetter will allow their teams to further expand their research in the field of neurodegenerative diseases. The Göttingen NMR experts also hope for new findings in cancer and infection research.

 "The scientific concept for purchase of this high-performance device had convinced the Max Planck Society's management which decided to finance the project. This unique state-of-the-art instrument will provide completely new insights into the structure and movements of biomolecules. This is a promising basis for groundbreaking findings," Max Planck President Martin Stratmann is pleased with the scientists about the new spectrometer.

The scientific concept was developed in collaboration with the University Medical Center Göttingen (UMG) and fit in with the orientation of the "Center for Biostructural Imaging of Neurodegeneration" (BIN), which Diethelm Richter initiated and planned together with other colleagues at the Göttingen Campus. The acquisition of the new NMR spectrometer required unusual mixed financing by the Max Planck Society, the German Research Foundation (DFG) and the State of Lower Saxony. The latter promoted this type of funding with great commitment: “The joint work at the Göttingen Campus between the University and research partners is already in a class of its own. These efforts are rewarded with one of the three internationally most powerful NMR spectrometers. The Göttingen scientists now have access to the most modern research facilities worldwide", says Björn Thümler, Lower Saxony's Minister of Science and Culture.

Wolfgang Brück, chairman of the executive board for research and education at UMG, states: "The new 1.2 GHz spectrometer will further strengthen the excellently positioned and state-of-the-art imaging portfolio at the Göttingen Campus. Research projects at the University Medical Center Göttingen will benefit from high-resolution NMR spectroscopy, especially through the established collaborations with research partners within the German Center for Neurodegenerative Diseases and the Center for Biostructural Imaging in Neurodegeneration. This will be an important future building block for the research and treatment of diseases in the fields of neurology and oncology."

Almost 600,000 times stronger than the earth's magnetic field

“NMR spectroscopy allows us to look at the mobility of atoms in a molecule in a broad range of time scales. The new device will enhance the sensitivity of our measurements by at least 60 percent compared to the existing 950 MHz instrument,” says Max Planck Director Griesinger. He is one of the world's leading experts in the development of methods for NMR spectroscopy and their application to biological problems. “Our scientists are always pushing boundaries. That means they need the instruments that push boundaries as well,” emphasizes Max Planck Vice President Asifa Akhtar. 

The teams of Griesinger and Zweckstetter as well as the research groups headed by Loren Andreas and Stefan Glöggler will use the high-performance instrument to characterize proteins that are difficult to study with other methods. These include membrane proteins or proteins that aggregate. “Such protein aggregations damage nerve cells, thereby contributing to neurodegenerative diseases such as Parkinson's and Alzheimer's,” explains Zweckstetter, professor at the UMG and group leader at the MPI for Biophysical Chemistry and the German Centre for Neurodegenerative Diseases (DZNE).

In the field of neurodegenerative diseases, Griesinger´s group, together with colleagues led by Armin Giese of the Ludwig-Maximilians-Universität (LMU) Munich, has already achieved promising results. In 2013, they developed a tailor-made molecule called anle138b, which slowed down protein aggregation as well as neuronal damage and death in mice. “The compound’s important feature is that it targets the protein aggregates and stops their formation,” the structural biologist explains. Anle138b is currently being tested in a clinical phase I trial by MODAG, a spin-off from the LMU and the Max Planck Society. “With the new 1.2 GHz instrument we hope to better understand the conformational changes that anle138b induces in the protein aggregates,” Griesinger says.

Other proteins are difficult to investigate because they are located on or inserted in a biological membrane. When these membrane proteins no longer function properly this can lead to severe disease. Membrane proteins, therefore, are targets for numerous drugs. “The new high-resolution spectrometer allows us to investigate such membrane proteins in their physiological environment,” reports Zweckstetter. The Göttingen researchers are currently carrying out research on proteins that enable infections by viruses, including influenza and the coronavirus.

A perfect home

A new hall for the high-performance instrument was built within 19 months considering special requirements: No steel was used and the new building had to be built with special regard to a stable working environment. Thick foundations make sure that no vibrations from inside or outside disturb the highly sensitive measurements. Not least, the experiments react to the smallest temperature fluctuations, so that high demands on the heating and ventilation systems had to be met.

It will take several weeks before the instrument is ready for research, however. First of all, the insulation shield of the helium and nitrogen reservoirs of the NMR spectrometer has to be pumped out – similar to a thermos flask – for approximately three weeks to generate the vacuum needed. In parallel, the magnet will be cooled down in two steps, first with liquid nitrogen to -196 °C, then with liquid helium to the final temperature of -271 °C. Only at these low temperatures will the superconducting coils inside the NMR spectrometer support the high current and high current density as well as the high magnetic field. Charging will commence after about four weeks.

The magnet coil is a new development of the company Bruker and comes as a sandwich: high-temperature superconductors for the inner coil and normal, low-temperature superconductors for the outer coil. Only with this special design can such a high, uniform magnetic field of 28.2 Tesla be generated. Once the Göttingen NMR magnet has reached this field, the spectrometer and probes can be tested and the first measurements undertaken. (cr/is)

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