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Heiko Möller - Uncovering molecular structures

Professor Heiko Möller enjoys looking beyond his own discipline. Möller teaches chemistry at the University of Constance and is a specialist in nuclear magnetic resonance spectroscopy. He enjoys working with other people, including colleagues from the field of chemistry and also biologists and tropical disease specialists. Heiko Möller returned from the USA to accept a junior professor position at Constance University.

Professor Möller has been working with nuclear magnetic resonance spectroscopy since he was a student in Hamburg. NMR spectroscopy is a standard method for the characterisation of organic molecules. However, it is not only organic chemistry that benefits from the wealth of information generated by this method, biological questions can also be clarified using NMR imaging.

When he was a graduate student in Hamburg, Professor Möller focused on the analysis of interactions between small molecules such as pharmaceutical substances or fragments of pathogens with macromolecular receptors (e.g. cell adhesion proteins). In Professor Bernd Meyer’s department in Hamburg, Möller investigated how HI viruses dock to host cells in order to develop molecules that prevent the intrusion of the viruses.

During his postdoc period in the USA at the Scripps Research Institute in San Diego, Möller focused on macromolecules (i.e. receptors) with the aim of elucidating the structure of proteins that bind to double-strand RNA (dsRNA). These processes play an important role in the development of cancer and viral infections.

Return to Germany from the USA

However, his stay in San Diego had quite a tricky start. He had barely set foot in San Diego, when Constance University began the search for a junior professor in “NMR spectroscopy of complex molecular systems”. The job description matched Möller’s qualifications and experience perfectly. However, as he had just arrived in San Diego the time didn’t really seem right to apply for the post. Nevertheless, Heiko Möller did exactly this and, as it turned out, luck was with him. The administrative process took rather a long time and he was able to stay in San Diego for one and a half years before finally returning to the German university.

One of Möller’s major projects relies on the discoveries he made in San Diego. Armed with what he found out about the molecular recognition of dsRNA, he uses NMR and other biophysical experiments to develop tiny molecules that bind to dsRNA with potentially interesting results. “This project requires in-depth know-how on ligand-based and receptor-based NMR spectroscopy,” said Prof. Möller highlighting a combination of skills that not everybody can offer.

The working conditions are pretty good in Constance, especially the view across the Lake Constance from his office on the 6th floor. However, more important than the pleasant view is his laboratory equipment that was upgraded with funds from the German government and the chemistry faculty. He has just put into operation a new 600 MHz NMR spectrometer equipped with a cryogenic probe head.
Professor Heiko Möller is junior professor of NMR spectroscopy at the University of Constance. (Photo: Keller-Ullrich)
His enthusiasm for this system, which cost about 1.2 million euros, clearly shows on Professor Möller’s face: An analysis that would have taken 36 hours with the old 600 system, now only takes one hour. “This enables us to analyse considerably smaller sample concentrations, something that is of great importance in biology,” said Möller.

Heiko Möller is in charge of setting up an NMR centre which also involves upgrading the laboratory equipment: The researchers will move their technology into the cellar, which is the best location for the highly sensitive devices that are easily disturbed by mobile phone aerials on the roof, solar irradiation or oscillations of the building. Möller, however, will be able to keep his office with the lake view.

Biological weapons – quick identification

NMR spectroscopy can take as long as several days, depending on the complexity of the molecule under investigation. It then takes weeks or months to analyse the signals and assemble them into a realistic picture. However, the effort is worth it, because the researchers’ work provides them with an exact, three-dimensional picture that is essential for researchers in different areas of expertise.

Möller is working with Professor Peter Seeberger from the ETH Zurich and Professor Gerd Pluschke from the Tropical Institute in Basel in a project focusing on the recognition of carbohydrate structures through antibodies that are specific for anthrax bacteria. This knowledge helps the scientists to quickly identify the typical characteristics of the dangerous bacteria without having to carry our too many syntheses. The findings from this project could promote the development of more effective, i.e. more reliable, rapid anthrax tests.

How nerves manage to grow again

Three-dimensional structure of the NfeD protein YuaF, which was determined using NMR spectroscopy (Figure: Möller)
Another of Möller’s major priorities is working with biologists on proteins (Reggie proteins) that are important for neuronal regeneration. These proteins are found in mammalian cells and the researchers already have a great deal of functional data at their disposition. However, highly resolved information on the molecular structure is still lacking.

Similar proteins also exist in bacteria, and are always found together with NfeD proteins. Since they are relatively easy to handle – they are very stable and can be labelled with isotopes – Professor Möller’s team is now investigating NfeD proteins in greater detail.

The researchers hope that the NfeD protein structures will provide them with information on the function of the Reggie proteins. The researchers’ goal is to find binding partners in eukaryotic cells and thus gain a better understanding of neuronal regeneration.

Neuronal regeneration works well in fish. If the optic nerve of a fish is injured, the fish nevertheless regain their vision six weeks later. The same is not true of human beings. Humans apparently have mechanisms that suppress this type of regeneration. That is why palsy is irreversible. The researchers also expect to gain new insights into other diseases of the nervous system such as Alzheimer’s, Parkinson’s or stroke. Professor Möller has just received a financial commitment from the DFG for his project.

mek – 26th June 2008
© BIOPRO Baden-Württemberg GmbH

Further information:
Department of Chemistry
University of Constance
Universitätsstraße 10
P.O. Box 715
78457 Konstanz
Tel.: +49 (0)7531 88-5174
Fax: +49 (0)7531 88-5149
E-mail: heiko.moeller@uni-konstanz.de
Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/heiko-moeller-uncovering-molecular-structures