Prof. Dr. Dietmar Manstein participates in RESIST research project D4.
| My Research Interest in RESIST |
Our aim in the context of RESIST is the development of new antiviral, antimicrobial and immunomodulatory agents that target the innate immune sensors cyclic GMP-AMP synthase (cGAS) and 2′-5′-oligoadenylate synthase (OAS). OAS and cGAS belong to the large and diverse superfamily of nucleotide triphosphate transferases. Both enzymes play key roles in the activation of interferon- driven antiviral responses upon recognition of pathogen-associated molecular patterns (PAMPs). In addition, these sensors constitute a continuous surveillance system for the presence of microorganisms in tissues.
We use a structure-based approach for the identification and optimization of highly specific small-molecule allosteric effectors of cGAS and OAS. This work is based on our comprehensive structural and mechanistic description of the complete enzymatic cycle of human cGAS and OAS. Validation of the compounds is performed in collaboration with RESIST scientists Thomas Pietschmann and Ulrich Kalinke.
Prof. Manstein about his scientific work
Prof. Dr. Dietmar Manstein – Curriculum Vitae
Current Position
Since 2002 Full (C4) Professor of Biophysical Chemistry and Director, Institute of Biophysical Chemistry, MHH
Since 2003 Director, Division of Structural Biochemistry, MHH
Since 2005 Director, Core Unit Laser Microscopy, MHH
Undergraduate and Postgraduate Training
1978 – 1983 Diploma Program in Biochemistry, Leibniz University Hannover (Thesis Supervisor: Prof. Dr. Jürg Rosenbusch, European Molecular Biology Laboratory, Heidelberg)
1984 – 1986 Natural Sciences Doctorat (Dr. rer. nat.), Ruprecht-Karls-Universität Heidelberg (Thesis Supervisor: Prof. Dr. Roger S. Goody, Max-Planck-Institute for Medical Research, Heidelberg)
1999 Habilitation in Biochemisty/Biophysics, Ruprecht-Karls-Universität Heidelberg (Supervisor: Prof. Dr. Felix Wieland, Faculty of Medicine, Ruprecht-Karls-Universität Heidelberg)
Academic and Research Posts
1983 Predoctoral Research Assistant, European Molecular Biology Laboratory, Heidelberg
1984 – 1986 Predoctoral Research Assistant, Max-Planck-Institut für Medizinische Forschung, Heidelberg
1986 – 1987 Postdoctoral Research Assistant, Max-Planck-Institute for Medical Research, Heidelberg (Director: Prof. Kenneth C. Holmes, FRS)
1987 – 1990 Postdoctoral Research Associate, Stanford University School of Medicine, USA (Postdoctoral advisor: Prof. J.A. Spudich)
1990 – 1996 Group Leader, National Institute for Medical Research, London, UK
1996 – 2002 Group Leader (C3), Max-Planck-Institute for Medical Research, Heidelberg
Since 2002 Professor of Biophysical Chemistry and Director, Institute of Biophysical Chemistry, MHH
Since 2003 Director, Division of Structural Biochemistry, MHH
Since 2005 Director, Core Unit Laser Microscopy, MHH
2018 – 2020 Deputy Director, Centre for Structural Systems Biology, Hamburg
Other Scientific Roles
1992 – 2019 Executive Editor Journal of Muscle Research and Cell Motility
2006 – 2012 Speaker, DFG-Research Unit FOR629 “Molecular Mechanisms of Cell Motility”
Since 2008 Editor FEBS Letters
2008 – 2011 Scientific delegate on behalf of the DFG, ERA-Instruments Scientific Advisory Board (European Research Infrastructures Working Group)
2008 – 2014 Representative of the German Structural Biology Community, German Committee for Synchrotron Research (KFS)
2009 – 2013 Representative for the State of Lower-Saxony on the Task Force for the Establishment of the Centre for Structural Systems Biology at DESY, Hamburg
Since 2011 Cofounding Editor FEBS OpenBio
Since 2013 Member of the Board of Directors – Centre for Structural Systems Biology (CSSB)
Since 2014 Member of the Academic Advisory Board, Hannover School for Biomolecular Drug Research (BMWZ)
Awards and Prizes
1985 DFG short-term Fellowship for research at the University of Michigan Medical School, Ann Arbor, MI, U.S.A.
1987 – 1989 DFG long-term Fellowship for research at Stanford University School of Medicine, Stanford, CA, U.S.A.
2002 Wellcome Trust University Award combined with the appointment to a full professorship, School of Biosciences, University of Kent, Canterbury, Kent, U.K. (not accepted)
2002 primo et unico loco – full professorship in Physiological Chemistry, Ruhr-Universität Bochum (not accepted)
Granted Patents
EP 2727911 B1 Dietmar J. Manstein, Matthias Preller, Markus Kalesse “Novel means and methods for treating malaria and other parasitic disorders” (published 21. Dec. 2016)
EP2277124 B1 Dietmar J. Manstein, Roman Fedorov, Georgios Tsiavaliaris, Hans-Joachim Knölker, René Martin, Juliane Kirst, Herwig Gutzeit, Markus Böhl, Marcus Furch, “Means for treating myosin- related diseases” (published 9. Nov. 2016)
US 9499471 B2 Dietmar J. Manstein, Matthias Preller, Marcus Furch, Markus Kalesse, Nina Díaz “Biphenyl compounds for use in treating malaria and other parasitic disorders” (published 22. Nov. 2016)
10 Selected Publications (of > 118 original publications)
Bratanov, D., Kovalev, K., Machtens, J.P., Astashkin, R., Chizhov, I., Soloviov, D., Volkov, D., Polovinkin, V., Zabelskii, D., Mager, T., Gushchin, I., Rokitskaya, T., Antonenko, Y., Alekseev, A., Shevchenko, V., Yutin, N., Rosselli, R., Baeken, C., Borshchevskiy, V., Bourenkov, G., Popov, A., Balandin, T., Buldt, G., Manstein, D.J., Rodriguez-Valera, F., Fahlke, C., Bamberg, E., Koonin, E. and Gordeliy, V. Unique structure and function of viral rhodopsins. Nat Commun 2019; 10: 4939. Doi: 10.1038/s41467-019-12718-0
Latham, S.L., Ehmke, N., Reinke, P.Y.A., Taft, M.H., Eicke, D., Reindl, T., Stenzel, W., Lyons, M.J., Friez, M.J., Lee, J.A., Hecker, R., Fruhwald, M.C., Becker, K., Neuhann, T.M., Horn, D., Schrock, E., Niehaus, I., Sarnow, K., Grutzmann, K., Gawehn, L., Klink, B., Rump, A., Chaponnier, C., Figueiredo, C., Knofler, R., Manstein, D.J.*, Di Donato, N.* Variants in exons 5 and 6 of ACTB cause syndromic thrombocytopenia. Nat Commun 2018; 9: 4250. Doi: 10.1038/s41467-018-06713-0 *joint senior author
Chinthalapudi K, Heissler SM, Preller M, Sellers JR, Manstein DJ. Mechanistic Insights into the Active Site and Allosteric Communication Pathways in Human Nonmuscle Myosin-2C. Elife 2017; 6. Doi: 10.7554/eLife.32742.
von der Ecken, J., Heissler, S.M., Pathan-Chhatbar, S., Manstein, D.J., Raunser, S. Cryo-EM structure of a human cytoplasmic actomyosin complex at near-atomic resolution. Nature 2016; 534: 724-728. Doi: 10.1038/nature18295
Hundt, N., Steffen, W., Pathan-Chhatbar, S., Taft, M.H., Manstein, D.J. Load-dependent modulation of non- muscle myosin-2A function by tropomyosin 4.2. Sci Rep 2016; 6: 20554. Doi: 10.1038/srep20554
Lohöfener, J., Steinke, N., Kay-Fedorov, P., Baruch, P., Nikulin, A., Tishchenko, S., Manstein, D.J., and Fedorov, R. The Activation Mechanism of 2′-5′-Oligoadenylate Synthetase Gives New Insights Into OAS/cGAS Triggers of Innate Immunity. Structure 2015; 23(5): 851-62. Doi: 10.1016/j.str.2015.03.012
Radke, M.B., Taft, M.H., Stapel, B., Hilfiker-Kleiner, D., Preller, M., Manstein, D.J. Small molecule-mediated refolding and activation of myosin motor function. Elife 2014; 3. Doi: 10.7554/eLife.01603
Behrmann, E., Müller, M., Penczek, P.A., Mannherz, H.G., Manstein, D.J.*, Raunser, S.* Structure of the rigor actin-tropomyosin-myosin complex. Cell 2012; 150: 327-338. Doi: 10.1016/j.bpj.2011.11.3105 *joint senior author
Fedorov, R., Böhl, M., Tsiavaliaris, G., Hartmann, F.K., Taft, M.H., Baruch, P., Brenner, B., Martin, R., Knölker, H.-J., Gutzeit, H.O., Manstein, D.J. The mechanism of pentabromopseudilin inhibition of myosin motor activity. Nat Struct Mol Biol 2009; 16: 80-88. Doi: 10.1038/nsmb.1542
Tsiavaliaris, G., Fujita-Becker, S., Manstein, D.J. Molecular engineering of a backwards-moving myosin motor. Nature 2004; 427: 558-561. Doi: 10.1038/nature02303
