At FZJ, diagnostics and therapeutics are being developed for inflammatory and degenerative CNS, infectious, and tumour diseases. Methodological focus is set on structure-based drug research, radio chemistry, and image based procedures for drug studies. In the areas of x-ray crystallography, as well as in liquid and solid state NMR spectroscopy, structural biology research is carried out at the highest international level.
Together with the Heinrich-Heine-University Düsseldorf (HHU) FZJ is running the Biomolecular NMR Center, which is one of the leading NMR centres in Germany and is an important partner within the Roadmap Structural Biology of the Helmholtz Association. One focus of the structural biological investigations is set on the characterization of protein ligand complexes and membrane proteins. In addition, chemical-analytical (LA-ICP-MS, AAS, GC-MS, LC-MS, FTICR-MS) and molecular biological methods (mirror image phage display) and innovative imaging techniques using high-end devices (high field MRI and PET hybrid approaches for humans and rodents) are applied.
Ultrasensitive assays for CSF and blood based lab diagnostics of neurodegenerative diseases (M. Alzheimer, M. Parkinson) are being developed. Clinical imaging procedures are the focus of the in vivo diagnostic approaches towards an early presymptomatic identification of neurologic and psychiatric diseases (schizophrenia, PSP, MSA, M. Alzheimer) as well as brain tumours. This includes research on radio diagnostic probes for molecular imaging using PET (amyloid imaging in dementias) and tracers for novel contrast agents to be used in high field MRI. Evaluated target structures and effectors are tested preclinically in model organisms and clinically in phases I to IIb (according to AMG).
The FZJ segment of the radionuclide based drugs creates a unique feature of the Helmholtz Association compared to other research collaboratives.
Kroll T, Elmenhorst D, Weisshaupt A, Beer S, Bauer A. Reproducibility of non-invasive A1 adenosine receptor quantification in the rat brain using [18F]CPFPX and Positron Emission Tomography. Mol Imaging Biol. (2014) 16(5):699-709.
Kroll T, Elmenhorst D, Matusch A, Wedekind F, Weisshaupt A, Beer S, Bauer A. Suitability of [18F]Altanserin and PET to determine 5-HT2A receptor availability in the rat brain: In vivo and in vitro validation of invasive and non-invasive kinetic models. Mol Imaging Biol. (2013) 15(4):456-467.
Elmenhorst D, Kroll T, Wedekind F, Weisshaupt A, Beer S, Matusch A, Bauer A. In vivo Kinetic and Steady-State Quantification of [18F]CPFPX Binding to Rat Cerebral A1 Adenosine Receptors: Validation by Displacement and Autoradiographic Experiments. J Nucl Med. (2013) 54(8):1411-1419.
Lecher J, Schwarz CKW, Stoldt M, Smits SHJ, Willbold D, Schmitt L. RTX toxin transporters tether its substrate prior to secretion via the unique function of its N- terminal domain. Structure 20, 1778-1787 (2012).
Schünke S, Stoldt M, Lecher J, Kaupp UB, Willbold D. Structural insights into conformational changes of a cyclic nucleotide-binding domain in solution from Mesorhizobium loti K1 channel. Proc. Natl. Acad. Sci. USA, 108, 6121-6126 (2011).
Zhang J., Baker M.L., Schröder G.F., Douglas N.R., Reissmann S., Jakana J., Dougherty M., Fu C.J., Levitt M., Ludtke S.J., Frydman J., Chiu W. Mechanism of folding chamber closure in a group II chaperonin. Nature. (2010) 463: 379-383.
Schröder G.F., Levitt M., Brunger A.T. Super-resolution biomolecular crystallography with low-resolution data. Nature. (2010) 464: 1218-1222.
Funke SA, van Groen T, Kadish I, Bartnik D, Nagel-Steger L, Brener O, Sehl T, Batra-Safferling R, Moriscot C, Schoehn G, Horn AHC, Müller-Schiffmann A, Korth C, Sticht H, Willbold D. Oral Treatment with the D-Enantiomeric Peptide D3 Improves Pathology and Behavior of Alzheimer’s disease Transgenic Mice. ACS Chem. Neurosci. 1, 639-648 (2010).
Müller-Schiffmann A, März-Berberich J, Andrjevna A, Rönicke R, Bartnik D, Brener O, Kutzsche J, Horn AHC, Hellmert M, Polkowska J, Gottmann K, Reymann K, Funke SA, Nagel-Steger L, Moriscot C, Schoehn G, Sticht H, Willbold D, Schrader T, Korth C. Combining independent drug classes into superior, synergistically acting hybrid molecules. Angew. Chem. Int. Ed. Engl. 49, 8743-8746 (2010).
Schwarten M, Mohrlüder J, Ma P, Stoldt M, Thielmann Y, Stangler T, Hersch N, Hoffmann B, Merkel R, Willbold D. Nix directly binds to GABARAP: A possible crosstalk between apoptosis and autophagy. Autophagy 5, 690-698 (2009).
Schünke S, Stoldt M, Novak K, Kaupp UB, Willbold D. Solution structure of the M.loti K1 channel cyclic nucleotide binding domain in complex with cAMP. EMBO Rep. 10, 729-735 (2009).
Glück JM, Wittlich M, Feuerstein S, Hoffmann S, König BW and Willbold D. Integral membrane proteins in nanodiscs can be studied by solution NMR spectroscopy. J. Am. Chem. Soc. 131, 12060-12061 (2009).
Stöhr J., Weinmann N., Wille H., Kaimann K., Nagel-Steger L., Birkmann E., Panza G., Prusinder S.B., Eigen M., Riesner D. Mechanisms of prion protein assembly into amyloid. Proc. Natl. Acad. Sci. USA. (2008) 105: 2409-2414.
Elfrink K., Ollesch J., Stoehr J., Willbold D., Riesner D., Gerwert K. Structural changes of membrane-anchored native PrPC. Proc. Natl. Acad. Sci. USA. (2008) 105: 10815-10819.