Forschungszentrum Jülich - FZJ
Multifold functionality and structure
Research at the Institute of Complex Systems (Structural Biochemistry, ICS-6) focusses on the investigation of three-dimensional structures and interactions of proteins, to elucidate how biological macromolecules perform their multitude of functions in cells and organism. Furthermore, the institute investigates pathways of misfolding and subsequent loss or gain of function, with the focus on proteins involved in the development and progression of neurodegenerative diseases like Alzheimer’s and Parkinson’s disease. Based on these insights the ICS-6 is developing new approaches for diagnosis and therapy, including their validation in vitro and in vivo. Scientists from a variety of disciplines like biochemistry, biology, chemistry, medicine, pharmacy and physics work together within the institutes’ interdisciplinary projects.
Successful progression of the research projects requires a wide array of methods from molecular biology and biophysics, as well as an excellent infrastructure of scientific large scale facilities. Highly sensitive, innovative and efficient methods from molecular biology, protein chemistry, biophysics, spectroscopy and microscopy are used in state-of-the-art lab spaces (security levels S1, S2 and S3**).
A particular strength is the development and application of nuclear magnetic resonance (NMR) spectroscopy for protein structure and dynamics investigation. Together with the Institute of Physical Biology at Heinrich-Heine-University Düsseldorf, the ICS-6 is running the Biomolecular NMR Center. Situated in Jülich, it hosts several high-field solution and solid state NMR devices in the range from 600 to 900 MHz, making it one of Germany’s leading NMR centers. In the coming years, the addition of a 800 MHz widebore DNP-NMR-Spectrometer and a 1.2 gigahertz NMR spectrometer will lead to a further increase in sensitivity and resolution, thereby establishing Jülich as an internationally unique location for NMR based structural biology.
To ensure access to the most suitable methods and infrastructures in all areas of structural biology research, the ICS-6 is engaged in strong collaborations on the local, national and international level. Cutting-edge equipment for X-ray crystallography is available, including measuring times at synchrotron beamlines, as well as access to neutron sources and supercomputers.
The broad expertise and excellent technological environment at ICS-6 provide ideal conditions to meet today’s most pressing challenges in health research.Insights provided by structural biology and their implementation in applied research go hand in hand.
The IBI-7 is part of the Institute of Biological Information Processing at Forschungszentrum Jülich. With more than 6,000 employees, Jülich – a member of the Helmholtz Association – is one of the large interdisciplinary research centres in Europe, pursuing cutting-edge interdisciplinary research on pressing issues facing society today. With its competence in materials science and simulation, and its expertise in physics, nanotechnology, and information technology, as well as in the biosciences and brain research, Jülich is developing the basis for the key technologies of tomorrow. In this way, Forschungszentrum Jülich helps to solve the grand challenges facing society in the fields of energy and the environment as well as information and the brain. Forschungszentrum Jülich is also breaking new ground in the form of strategic partnerships with universities, research institutions, and industry in Germany and abroad.
Kutzsche J, Jürgens D, Willuweit A, Adermann K, Fuchs C, Simons S, Windisch M, Hümpel M, Rossberg W, Wolzt M, Willbold D. Safety and pharmacokinetics of the orally available antiprionic compound PRI-002: A single and multiple ascending dose phase I study. Alzheimers Dement (N Y) 6, e12001 (2020). PubMed
Röder C, Kupreichyk T, Gremer L, Schäfer LU, Pothula KR, Ravelli RBG, Willbold D, Hoyer W, Schröder GF. Cryo-EM structure of islet amyloid polypeptide fibrils reveals similarities with amyloid-β fibrils. Nat. Struct. Mol. Biol. (2020). doi: 10.1038/s41594-020-0442-4. PubMed
Frieg B, Gremer L, Heise H, Willbold D, Gohlke H. Binding modes of thioflavin T and Congo red to the fibril structure of amyloid-β(1-42). Chem Commun (Camb). 56, 7589-7592. doi: 10.1039/d0cc01161d (2020). PubMed
Röder C, Kupreichyk T, Gremer L, Schäfer LU, Pothula KR, Ravelli RBG, Willbold D, Hoyer W, Schröder GF. Cryo-EM structure of islet amyloid polypeptide fibrils reveals similarities with amyloid-β fibrils. Nat Struct Mol Biol. 27, 660-667, doi: 10.1038/s41594-020-0442-4 (2020). PubMed
Zabelskii D, Alekseev A, Kovalev K, Rankovic V, Balandin T, Soloviov D, Bratanov D, Savelyeva E, Podolyak E, Volkov D, Vaganova S, Astashkin R, Chizhov I, Yutin N, Rulev M, Popov A, Eria-Oliveira AS, Rokitskaya T, Mager T, Antonenko Y, Rosselli R, Armeev G, Shaitan K, Vivaudou M, Büldt G, Rogachev A, Rodriguez-Valera F, Kirpichnikov M, Moser T, Offenhäusser A, Willbold D, Koonin E, Bamberg E, Gordeliy V. Viral rhodopsins 1 are an unique family of light-gated cation channels. Nat. Commun. 11, 5707, doi: 10.1038/s41467-020-19457-7 (2020). PubMed
Perov S, Lidor O, Salinas N, Golan N, Tayeb-Fligelman E, Deshmukh M, Willbold D, Landau M. Structural Insights into Curli CsgA Cross-β Fibril Architecture Inspire Repurposing of Anti-amyloid Compounds as Anti-biofilm Agents. PLoS Pathog. 15, e1007978 (2019). PubMed
Schemmert S, Schartmann E, Zafiu C, Kass B, Hartwig S, Lehr S, Bannach O, Langen KJ, Shah NJ, Kutzsche J, Willuweit A, Willbold D. Aβ Oligomer Elimination Restores Cognition in Transgenic Alzheimer's Mice with Full-blown Pathology. Mol Neurobiol. 56, 2211-2223 (2019). PubMed
Röder C, Vettore N, Mangels LN, Gremer L, Ravelli RBG, Willbold D, Hoyer W, Buell AK, Schröder GF. Atomic structure of PI3-kinase SH3 amyloid fibrils by cryo-electron microscopy. Nat Commun. 10, 3754 (2019). PubMed
Gremer L, Schölzel D, Schenk C, Reinartz E, Labahn J, Ravelli R, Tusche M, Lopez-Iglesias C, Hoyer W, Heise H, Willbold D, Schröder GF. Fibril structure of amyloid-ß(1-42) by cryo-electron microscopy. Science 358, 116-119 (2017). PubMed
Gushchin I, Melnikov I, Polovinkin V, Ishchenko A, Yuzhakova A, Buslaev P, Bourenkov G, Grudinin S, Round E, Balandin T, Borshchevskiy V, Willbold D, Leonard G, Büldt G, Popov A, Gordeliy V. Mechanism of transmembrane signaling by sensor histidine kinases. Science. 356, eaah6345 (2017). PubMed
Volkov O, Kovalev K, Polovinkin V, Borshchevskiy V, Bamann C, Astashkin R, Marin E, Popov A, Balandin T, Willbold D, Büldt G, Bamberg E, Gordeliy V. Structural insights into ion conduction by channelrhodopsin 2. Science 358, eaan8862 (2017). PubMed
Dick M, Hartmann R, Weiergräber OH, Bisterfeld C, Classen T, Schwarten M, Neudecker P, Willbold D, Pietruszka J. Mechanism-based inhibition of an aldolase at high concentrations of its natural substrate acetaldehyde: structural insights and protective strategies. Chem. Sci. 7, 4492-4502 (2016). PubMed