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. 

Contact

Prof. Manstein about his scientific work

Prof. Dr. Dietmar Manstein – Curriculum Vitae

Current Positions

  • 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, Research Unit for Structural and Computational Biology, European Molecular Biology Laboratory, Heidelberg

  • 1984 – 1986 Predoctoral Research Assistant, Department of Biophysics, Max-Planck-Institut für Medizinische Forschung, Heidelberg

  • 1986 – 1987 Postdoctoral Research Assistant, Department of Biophysics, Max-Planck-Institute for Medical Research, Heidelberg (Director: Prof. Kenneth C. Holmes, FRS) 

  • 1987 – 1990 Postdoctoral Research Associate, Department of Cell Biology, Stanford University School of Medicine, USA (Postdoctoral advisor: Prof. J.A. Spudich)

  • 1990 – 1996 Group Leader, Division of Physical Biochemistry, National Institute for Medical Research, London, UK

  • 1996 – 2002 Group Leader (C3), Department of Biophysics, 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

  • 2006 – 2022 Member, Senate Sub-committee for Research

  • 2009 – 2013 Member of the MHH Senate

  • 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

  • 2011 – 2014 Managing Director, MHH Research Core Facilities

  • since 2013  Member of the Board of Directors – Centre for Structural Systems Biology (CSSB)

  • since 2015  Chair, Advisory Board on IT-Infrastructure for Research, MHH

  • 2015 – 2019 Member of the MHH Senate, Speaker of the professorial group

  • 2019 – 2023 Deputy member of the MHH Senate

  • 2018 – 2020 Deputy Director, Centre for Structural Systems Biology, Hamburg

  • since 2023  Member of the Clinical Committee of MHH

  • since 2023  Deputy member of the Commission for Research Ethics at MHH

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, a non-profit scientific journal of the Federation of European Biochemical Societies

  • 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 – 2015 Member of the Working Group on Drug Research of the Arbeitsgemeinschaft Internistische Onkologie in der Deutschen Krebsgesellschaft e. V. (AIO)

  • 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, a non-profit scientific open access journal of the Federation of European Biochemical Societies

  • 2014 – 2020 Member of the Academic Advisory Board, Hannover School for Biomolecular Drug Research (BMWZ) 

Awards and Prizes

  • 1984 – 1987 Max Planck Research Fellowship

  • 6/1984 Teilnahme als Nachwuchs-Wissenschaftler an der 34. Tagung der Nobelpreisträger in Lindau mit den Schwerpunkten Physiologie und Medizin

  • 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.

  • 2000 – 2001 Visiting professorship at the National Institute of Information and Communications Technology, Kobe Advanced ICT Research Centre in Nishi-ku, Kobe, Japan

  • 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)

  • 11/2004 DFG HighLight2004 Award für Höchsleistungslichtmikroskopie (1.1 Mio. €)

  • 6/2005 Teilnehmer am Nobel Symposium 131 „Controlled Nanoscale Motion“in Bäckaskog, Schweden

  • 3/2018 Lokey Center Distinguished Lecturer, Technion–Israel Institute of Technology, Haifa, Israel

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) 

Recommended Links

For further information about Prof. Manstein’s scientific work please check the following links:

10 Selected Publications

1. 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.

2. 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

3. 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

4. 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

5. 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

6. Münnich, S., Taft, M.H., Manstein, D.J. Crystal Structure of Human Myosin 1c – The Motor in GLUT4 Exocytosis: Implications for Ca2+ Regulation and 14-3-3 Binding. J Mol Biol 2014; 426: 2070-2081. Doi: 10.1016/j.jmb.2014.03.004

7. 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

8. 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

9. Reubold, T.F., Eschenburg, S., Becker, A., Leonard, M., Schmid, S.L., Vallee, R.B., Kull, F.J., Manstein, D.J. Crystal structure of the GTPase domain of rat dynamin 1. Proc Natl Acad Sci USA 2005; 102: 13093-13098. Doi: 10.1073/pnas.0506491102

10. 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

Contact

  Prof. Dr. Dietmar Manstein
  Institute for Biophysical Chemistry,
Hannover Medical School (MHH)
  Carl-Neuberg-Str. 1
30625 Hannover
  +49 511 532 – 3700
  Manstein.Dietmar
@mh-hannover.de