Am Anfang steht eine kurze Einleitung in die Methode der kernmagnetischen Resonanz, mit Hilfe derer wir die Struktur von Biomolekülen mit einer Auflösung im sub-Ångström Bereich bestimmen und die Geschwindigkeit von Strukturänderungen der Biomoleküle im Bereich von Picosekunden bis Sekunden messen können. Dann wird die Methode auf die Untersuchung der Faltung von aggregierenden Proteinen, die mit neurodegenerativen Erkrankungen im Zusammenhang stehen, angewandt. Z.B. aggregiert das Protein α-Synuclein in Patienten mit Parkinson oder Multisystematrophie, die Proteine Amyloid-β und tau bei der Alzheimer Erkrankung und das Protein Insel-Amyloid-Polypeptid (IAPP) beim Altersdiabetes. Wir erhalten mittels NMR Einblick in den Aggregationsprozess (1) und sind dabei besonders interessiert an den Aggregationsspezies, die besonders schädlich für den Organismus sind (2). Darüberhinaus ermitteln wir die Wirkungsweise therapeutischer und diagnostischer Moleküle, die die toxischen Aggregate “unschädlich” machen (3) und ermitteln Strukturinformation darüber.
References:
1) L. Antonschmidt, R. Dervişoğlu, V. Sant, K. A. Tekwani Movellan, I. Mey, D. Riedel, C. Steinem, S. Becker, L. B. Andreas, C. Griesinger. Insights into the molecular mechanism of amyloid filament formation: segmental folding of α-synuclein on lipid membranes/Molecular mechanism of αS filament folding on membranes, Sci. Adv. 7(20) eabg2174
2) Vrinda Sant, Dirk Matthes, Hisham Mazal, Leif Antonschmidt, Franz Wieser, Kumar T. Movellan, Kai Xue, Evgeny Nimerovsky, Magdeline Nathan, Stefan Becker, Vahid Sandoghdar, Bert deGroot, Christian Griesinger, Loren Andreas Structure of a lipidic α-Synuclein misfolded aggregation intermediate https://doi.org/10.21203/rs.3.rs-4437173/v1 Nat. Comm. provisionally accepted
3) J. Wagner, S. Ryazanov, A. Leonov, J. Levin, S. Shi, F. Schmidt, C. Prix, F. Pan-Montojo, U. Bertsch, G. Mitteregger-Kretzschmar, M. Geissen, M. Eiden, F. Leidel, T. Hirschberger, A. A. Deeg, J. J. Krauth, W. Zinth, P. Tavan, J. Pilger, M. Zweckstetter, T. Frank, M. Bähr, J. H. Weishaupt, M. Uhr, H. Urlaub, U. Teichmann, M. Samwer, K. Bötzel, M. Groschup, H. Kretzschmar, C. Griesinger, A. Giese, “Anle138b: a novel oligomer modulator for disease-modifying therapy of neurodegenerative diseases such as prion and Parkinson’s disease”, Acta Neuropathol. 125, 795-813 (2013); M. Wegrzynowicz, D. Bar-On, L. Calò, O. Anichtchik, M. Iovino, J. Xia, S. Ryazanov, A. Leonov, A. Giese, J. Dalley, C. Griesinger, U. Ashery, M.-G. Spillantini. “Depopulation of α-synuclein aggregates is associated with rescue of dopamine neuron dysfunction and death in a new Parkinson disease model” Acta Neuropathol. 138, 575-595 (2019); J. Levin, N. Sing, S. Melbourne, A. Morgan, M.-G. Spillantini, M. Wegrzynowicz, J.W. Dalley, S. Ryazanov, A. Leonov, C. Griesinger, F. Schmidt, D. Weckbecker, K. Prager, T. Matthias, A. Giese, Safety, tolerability and pharmacokinetics of the oligomer modulator anle138b with exposure levels sufficient for therapeutic efficacy in a murine Parkinson model: a randomised, double-blind, placebo-controlled phase 1 trial EBioMedicine 80, 104021 (2022); NCT04685265; NCT06568237
4) Benedikt Frieg, Leif Antonschmidt, Christian Dienemann,James A. Geraets, Dirk Matthes, Bert de Groot, Stefan Becker, Loren B. Andreas, Christian Griesinger, Gunnar F. Schröder. „Lipid-induced polymorphism of α-synuclein fibrils” Nature Commun. 13, 6810 (2022); L. Antonschmidt, R. Dervişoğlu, D. Matthes, C. Dienemann, A. Leonov, V. Sant, S. Ryazanov, S. Becker, A. Giese, Gunnar Schröder, B. de Groot, C. Griesinger, L. B. Andreas. “The small molecule drug candidate anle138b is incorporated into α-synuclein fibrils” Nat. Commun. (2022) 13:5385; B. Frieg, M. Han, K. Giller, C. Dienemann, D. Riedel, S. Becker, L.B. Andreas, C. Griesinger, G.F. Schröder. Cryo-EM structures of lipidic fibrils of amyloid-β(1-40): Nature Commun. 15, 1297 (2024)
Education
1979 – 1982 Chemistry and Physics, University of Frankfurt, Germany
1982 Prediploma in Physics, University of Frankfurt, Germany
1984 Chemistry, University of Frankfurt, Germany, Diploma (summa cum laude; Mentor: H. Kessler)
1984 – 1986 Chemistry, University of Frankfurt, PhD (summa cum laude; Mentor: H. Kessler)
1986 – 1989 Postdoctoral fellow in the laboratory of Physical Chemistry, ETH Zurich (Mentor: R. R. Ernst)
Research Experience
2001 – Honorary Professor, University of Göttingen
July 1999 – Department Director and Scientific Member at Max Planck Institute for Multidisciplinary Sciences (Biophysical Chemistry till 2021), Göttingen
Jan 1990 – Sept. 2000 Full Professor for Organic Chemistry, University of Frankfurt
Community Service:
2021 Organizer of the German NMR meeting (zoom)
2020-2024 Member of the board of Focus group magnetic resonance of the German Chemical
Society (GDCh)
2020-2022 Co-Organizer of the lecture series: Emerging topics in Magnetic Resonance (zoom)
2020- Eccelenza Panel of the Swiss National Fund/co-chair since 2022
2019- IAB of ICRI-BioM
2017/2019 Vice chair and chair of the Gordon conference for magnetic resonance
2016 Panel of the Norwegian science foundation on life sciences
Since 2015 SAB of CicBioGune, Bilbao, Spain
2015 Panel of Swiss National Science Foundation
2014,16,18,20 ERC advanced grant panel LS1
Since 2013- IAB member of uNMR-NL
Since 2012- SAB of TGIR RMN THC
2007- Member of the Göttingen Research Council (-2011, since then deputy)
2007-2008 Managing Director of the Max Planck Institute for Biophysical Chemistry
2007 Organizer of the German NMR meeting, Göttingen (250 participants)
2006 Organizer of the ICMRBS Göttingen (850 participants)
2006- Main organizer of EMBO course: “Advanced biomolecular NMR (biannual)”
2006-2012 Member of and Chairperson of (since 2009) of the SAB of FMP, Berlin
2005 – Mentor of MPG (until 2009) and of MPI (from 2009) Partner group at UN Rosario
and since 2013 of Max Planck Laboratory (Claudio Fernandez)
2004 -2012 DFG study section member: Basics of Biology and Medicine
2004 – Associate Editor for FEBS letters
2002- 2012 Member of the Russel Varian prize committee (15.000 € prize)
2002-2010 Member of the EUROMAR committee
2000 Chair of the Executive Committee of the 41st ENC, Asilomar, CA, USA
(1500 participants)
1997 – Associate Editor of Journal of Magnetic Resonance
1997 – 2001 Contact Professor for the Fonds der Chemischen Industrie
1995 – 2000 Codirector of the Large Scale Facility of Biomolecular NMR , University of Frankfurt
1995 – 2001 Member of the Executive Committee of the ENC
1994 – 1996 Member and 1997-2000 Chairman of the Executive Committee of GDCH subgroup Magnetic Resonance Spectroscopy;
1994 – Member of the GDCh
1993 – 1997 Chair of the Institute for Organic Chemistry, University of Frankfurt
Honors and Awards `
2023 Honorary Member of the Magnetic Resonance Society of Japan
2019 Günther Laukien prize awarded at ENC, Asilomar, CA, USA.
2016 KMRS prize (Korean magnetic resonance society)
2014 Ampere Prize received at EUROMAR, Zürich
2014- Corresponding Member of the Bavarian Academy of Sciences
2013 Dr. h.c. University of Rosario, Argentina & Recognition by the house of representatives of Argentina, Buenos Aires, Argentina
2012 Theodor Bücher award Lecture held at FEBS and IUBMB congress, Sevilla, Spain
2011 Elected member of EMBO
2011 ELHUYAR-GOLDSCHMIDT prize of the Royal Society of Spain and the GDCH
2009 Honorary member of the National Magnetic Resonance Society (India)
2008 ERC Advanced grant: HiddentimeNMR
2008 Elected Member of the National Academy of Sciences, Leopoldina
2007 – Elected member of the Academy of Sciences of Goettingen
2003 Otto-Bayer-Prize
1998 Leibniz Prize of the Deutsche Forschungsgemeinschaft
1998 Cofounder of MRPHARM
1997 Sommerfeld Prize of the Bavarian Academy of Science
1996 Prize for the best Chemistry Book of the Fonds der Chemischen Industrie together with Prof. Quinkert and Prof. Egert for “Aspects of Organic Chemistry”
1989 Young Scientist’s Stipend of the Fonds der Chemischen Industrie
1987 PhD award, University of Frankfurt
1986 Stipend of the Fonds der Chemischen Industrie for finish of the PhD study
1984 – 1986 Stipend of the Fonds der Chemischen Industrie for PhD students
1979 – 1984 Member of the Studienstiftung des Deutschen Volkes
1978 Bronze Medal. International Chemistry Olympiade, Torun Poland
Other activities `
2013 Cofounder of MODAG GmbH
1998 Cofounder of MRPHARM GmbH
Research Interests
– Synthesis and elucidation of structure and dynamics of biologically active molecules (peptides, DNA, RNA, oligosaccharides) using NMR spectroscopy in solution and in the solid state.
– Methods- and software development for multidimensional NMR spectroscopy
– Elucidation of mechanisms of Enzymes
– Structural biology of neurodegenerative diseases and immunologically interesting proteins, interference with neurodegeneration
– Transmembrane signalling
– Stereochemistry of natural products