The research group leader at the Max Planck Institute (MPI) for Biophysical Chemistry receives 2.4 million euros of funding from the European Research Council (ERC) for the next five years. With the help of this funding, the physical chemist and her team want to combine two methods: nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) spectroscopy. By doing this, the researchers aim to develop more sensitive techniques with higher resolution to study, for example, interactions between proteins and drugs.
How do proteins regulate biological processes in our bodies? How are they activated and how inhibited? And where do drugs bind with biomolecules? To better observe these processes at a molecular level, Bennati and her team want to further develop techniques in NMR and EPR spectroscopy: “Magnetic resonance is one of the most important methods in natural sciences for studying the structure and function of molecules. However, the two techniques are often not sensitive enough to give us all the answers,” explains Bennati, who heads an independent research group at the MPI for Biophysical Chemistry and is a professor in the department of chemistry at the University of Göttingen.
One of the proteins targeted by the researchers is ribonucleotide reductase (RNR), an enzyme which helps to manufacture vital components for our genetic information. Bennati wants to elucidate how RNR is activated and inhibited. Since the RNR is also an important target for anti-cancer drugs, this knowledge could help develop new agents. “Our lab possesses suited expertise and state-of-the-art EPR and NMR instruments to gain deeper insights into such regulatory mechanisms,” the scientist emphasizes.
One phenomenon, two different methods
EPR and NMR spectroscopy are based on the phenomenon of magnetic resonance. This occurs because electrons and atomic nuclei all have a spin and therefore align themselves with strong magnetic fields. NMR spectroscopy is based on the fact that different atomic nuclei behave differently under the influence of strong magnetic fields. This allows conclusions about neighboring atoms and thus the structure of biomolecules.
Unpaired electrons are also magnetically active and serve as highly sensitive probes for researchers. EPR spectroscopy is based on this technique. Even though only molecules with unpaired electrons are suitable for EPR spectroscopy, the results of this method are three orders of magnitude more sensitive than those of NMR spectroscopy.
Bennati and her team are trying to combine the best of both worlds: They use EPR-based methods and simultaneously measure resonance signals of the atomic nuclei. Also, they use NMR-based techniques, but add molecules whose unpaired electrons make the method more sensitive. “In a nutshell, we use NMR methods to improve EPR and vice versa,” the Göttingen physical chemist sums up. “Thanks to the approved ERC Advanced Grant, we can now develop new strategies to amplify magnetic resonance signals to achieve higher resolution and sensitivity.”
This year, four researchers from Lower Saxony successfully applied for ERC Advanced Grants, three of them from Göttingen: In addition to Marina Bennati, her colleague Lutz Ackermann at the University of Göttingen´s faculty of chemistry and Alexander Flügel at the University Medical Center Göttingen received grants worth millions.