AAU logo

NMR Spectroscopy

NMR Spectroscopy

NMR Spectroscopy

Research Interests

The common theme of all our research is NMR spectroscopy, applied to biomolecular or biotechnological questions.

Antimicrobial Peptides

Research into AMPs is triggered by the fact that more and more human pathogens acquire resistance against multiple common, but also “last-resort”, antibiotics. AMPs are thought to offer a completely new class of antibiotics: they are widely abundant in nature, virtually every organism uses them. Moreover, it seems to be very difficult for bacteria to acquire resistance against AMPs, although some mechanisms of resistance are described in the literature

During the past years, we have been working on several different AMPs. A common topic has always been the determination of AMP structure and its link to activity studies. We developed a method to reliably establish orientation and insertion of peptides into micelles and developed a method relying on paramagnetic environment relaxation enhancement 1. (Independently, the Zangger research group at the University of Graz, Austria, developed a method based on the same basic idea, however with a completely different computational approach 2.)

 
Left: PREs provide distance constraints from the micelle center to almost each Hα atom of the peptide, defining peptide position in the micelle (shown as green sphere); Right:Structure and micelle immersion of a short helical antimicrobial peptide, determined by PREs.

As part of the Danish Center for Antibiotic Research and Development (DanCARD), we investigate structure-activity relationships of helical AMPs and structural implications of different peptidomimetics.

In a continuous collaboration with an industrial partner (Novozymes), we also worked on structural and activity studies of another class of AMPs – b-defensins. As part of a bigger study, we investigated the structural aspect of ligand binding of plectasin, an AMP from a fungus. This work was part of a large study finally published in the renowned international journal “Science” 3. We then demonstrated that also another fungal defensin called “eurocin” had a similar structure and targeted the same ligand 4. In a smaller study we showed that also a defensin from insects followed the same trend – however, with some subtle differences 5.


A: structure of plectasin with the interaction epitope with the micelle. B: structure of plectasin with lipid II modelled by HADDOCK and the interaction epitope with lipid II shown in magenta. Figure from 3.

Calmodulin-receptor interactions

Calmodulin is nature’s universal Ca2 sensor and Ca2 -dependent regulatory protein. Recently, the first human calmodulin mutations (N97S and N53I) in the CALM1 gene were discovered 6. They are linked to a severe dominantly inherited form of ventricular tachycardia (CPVT). In collaboration with Michael Overgaard, we work on understanding the structural background for the detrimental effect of these mutations.

Metabolomics in Medicine

We collaborate with Aalborg and Aarhus hospitals on metabolomics projects in certain diseases.

Metabolite Profiling

As part of the the Center for Microbial Communities, we work with metabolite profiling of bacteria from wastewater treatment plants, feeding them with isotope labelled substrates and analyzing, where the substrates go.

Cyclodextrin Technology

When we get tired of all the BIO-stuff, we turn to the Supramolecular Chemistry research group, where there is always an interesting cyclodextrin host-guest complex to be investigated!

Project leader

Professor with Specific Responsibilities
Reinhard Wimmer

Aalborg University
Department of Biotechnology, Chemistry and Environmental Engineering
Fredrik Bajers Vej 7H
9220 Aalborg East
Denmark

Tel.: ( 45) 9940 8518
Email: rw@bio.aau.dk

CV
Publications
Press clippings

References

  1. Franzmann M, Otzen D, Wimmer R (2009) Quantitative Use of Paramagnetic Relaxation Enhancements for Determining Orientations and Insertion Depths of Peptides in Micelles. Chembiochem 10:2339–2347.
  2. Zangger K, Respondek M, Gobl C, Hohlweg W, Rasmussen K, Grampp G, Madl T (2009) Positioning of micelle-bound peptides by paramagnetic relaxation enhancements. J Phys Chem B 113:4400–6.
  3. Schneider T, Kruse T, Wimmer R, Wiedemann I, Sass V, Pag U, Jansen A, Nielsen AK, Mygind PH, Raventós DS, et al. (2010) Plectasin, a Fungal Defensin, Targets the Bacterial Cell Wall Precursor Lipid II. Science (80- ) 328:1168–1172.
  4. Oeemig JS, Lynggaard C, Knudsen DH, Hansen FT, Noergaard KD, Schneider T, Vad BS, Sandvang D, Nielsen LA, Neve S, et al. (2012) Eurocin, a new fungal defensin: structure, lipid binding and its mode of action. J Biol Chem 287:42361–42372.
  5. Nygaard MKE, Andersen AS, Kristensen H-H, Krogfelt KA, Fojan P, Wimmer R (2012) The insect defensin lucifensin from Lucilia sericata. J Biomol NMR 52:277–282.
  6. Nyegaard M, Overgaard MT, Søndergaard MT, Vranas M, Behr ER, Hildebrandt LL, Lund J, Hedley PL, Camm AJ, Wettrell G, et al. (2012) Mutations in Calmodulin Cause Ventricular Tachycardia and Sudden Cardiac Death. Am J Hum Genet 91:703–712.