Matthias Elgeti has seen a lot in his scientific career, even working with Nobel Prize winners. But his first challenge at his new place of work, the Faculty of Medicine, was a very special one: how do you move an EPR spectrometer into a basement laboratory? Weighing in at 1.7 tonnes, the magnet – the heart of this piece of measuring equipment – was simply too heavy to take the lift. But scientists have a reputation for finding answers to tricky questions. Thanks to some very clever tinkering, it was possible to quickly increase the lift’s maximum load.
EPR stands for electron paramagnetic resonance, and an EPR spectrometer allows the precise study of the interaction of microwave radiation with unpaired electrons. Since unpaired electrons do not occur very often in nature, Dr Elgeti uses such electrons as artificial probes to study proteins very precisely with EPR. The EPR spectrometer is now in its new home and Dr Elgeti has already started his work.
“EPR is a huge toolbox with many different applications. We use the methods to study the structure and dynamics of proteins. We are particularly interested in how drugs interact with proteins to produce their effect,” explains Dr Elgeti. The scientist is interested in a number of questions: how do proteins themselves work, how do they change shape and how can they be controlled with drugs? In this way, he hopes to contribute to the development of new, improved drugs with fewer side effects.
Receptors as key regulators of bodily functions
In his new research group at the Institute for Drug Discovery, led by Humboldt Professor Jens Meiler, he is investigating, among other things, Y receptors, which regulate important functions in the body. These include the feeling of hunger, the rhythm of day and night, but also fear. “We are trying to understand the four Y-family receptors and their differences in detail so that we can develop drugs that have only the desired effects and no side effects.” Explaining his role at the institute, Dr Elgeti continues: “I see basic research as an essential part of any medical school. Medicine begins with an understanding of the body’s basic reactions, which enables rational, successful treatment of patients. To properly train the scientists and doctors of tomorrow, you also need people with giant magnets in their basement studying how proteins move.”
The biophysicist recently published a preprint, in collaboration with the research group of Nobel laureate Brian Kobilka (Stanford University), on one of the opioid receptors that regulates the sensation of pain, among other things. Drugs that act on this receptor sometimes have serious side effects and can be highly addictive. Thousands of people die every day from overdoses of opioids like fentanyl. So the researchers looked at the molecular causes of these powerful compounds.
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To teach the new EPR technology and the necessary basics, a seminar entitled Integration of Experimental Data with Artificial Intelligence for the Investigation of Membrane Proteins will be held at Leipzig University from 5 to 9 June for doctoral researchers, postdocs and interested students. Besides the theoretical basics for the investigation of membrane structures by NMR and EPR, the seminar will focus on integrative AI-mediated analysis, an innovative approach. Vanderbilt professors Professor Hassane Mchaourab, who is involved in CRC 1423 as a Mercator Professor, and Professor Erkan Karakas, as well as Professor Jens Meiler and Dr Matthias Elgeti from Leipzig University, will participate in the event.
The course was initiated by Professor Meiler and Professor Annette Beck-Sickinger, who have been coordinating the partnership between Leipzig and Vanderbilt University in Nashville since 2006. “Our collaboration with Vanderbilt University is an excellent combination of cutting-edge research and international training for students, doctoral researchers and academic staff,” says Beck-Sickinger. “This partnership is also an important cornerstone of scientific exchange and the promotion of early career researchers under DFG Collaborative Research Centre 1423,” adds the CRC spokesperson.
Collaborative Research Centre 1423: Structural Dynamics of GPCR Activation and Signaling.