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Prof. Dr. Dietmar J. Manstein

PhD 1986 Heidelberg, 1987 - 1990 Postdoctoral work at Stanford University School of Medicine, USA.
1990 - 1996 Group Leader at the National Institute for Medical Research, London, UK. 
1996 - 2002 Senior Group Leader at the Max-Planck-Institute for Medical Research, Heidelberg.
2002 -  Director of the Institute for Biophysical Chemistry at MHH
2003 -  Director of the Division for Structural Biochemistry at MHH
2013 -  Member of the Board of Directors of the Centre for Structural Systems Biology at DESY, Hamburg.


Research Interests


Actin, dynamin, myosin, tropomyosin, intracellular pathogen sensors; protein structure, dynamics, reaction mechanisms, and allostery; cell motility, cytoskeletal dynamics; pharmacological chaperone-based approaches to treat muscle disorders and cytoskeletal protein-linked diseases; small-molecule based approaches to prevent and treat sepsis




Macromolecular X-ray crystallography; computer-assisted drug-design; time-resolved spectroscopy; transient kinetics; analytical ultracentrifugation; microscale thermophoresis; calorimetry (DSC and ITC); differential scanning fluorescence (ThermoFluor assay); circular dichroism spectroscopy; single molecule and live-cell imaging approaches; eukaryotic protein expression; bioinformatics for integrated structural biology and hybrid methods.


Research Profile


The objective of my work is the characterization of molecular motors and proteins that regulate dynamic changes of cytoskeletal and membranous structures. The coordinated generation of movement and force is essential for basic processes such as cell division, chromosome segregation, endocytosis, exocytosis, axonal transport, and muscle contraction.
Elucidation of the molecular mechanisms underlying motile events is of significance with respect to a wide range of health related issues, such as neurodegeneration, heart failure, skeletal muscle myopathies, cell-mediated immune response, wound healing, and the invasion of healthy tissue by malignant tumor cells.
Our experiments address the role of isoform-specific differences, disease-causing mutations, and drugs by integrating information derived from examining contractile events at several levels of organization. At the single molecule level, the work examines the basic design and function of the molecular motors, actin filaments, and regulatory proteins using highly-sensitive and fast techniques to follow chemical, spectroscopic, and mechanical changes. These studies are usually combined with protein engineering and high-resolution structural analyses. The determination of three-dimensional structures of bio-macromolecules and their complexes with small ligands is performed using X-ray crystallography. The results of these measurements provide insights into the catalytic mechanism of enzymes, the mode of action of small-molecule effectors, and support the development of therapeutic drugs. Hybrid approaches, which combine analysis by X-ray crystallography with cryo-electron microscopy or the analysis of hydrodynamic properties, are used to solve the structures of larger protein complexes. Here, the results can provide insights into long-range communication pathways, regulatory mechanisms, and the effects of disease causing mutations. At the level of isolated cells, our research program uses the information gained from kinetic and structural studies, to address the role of specific contractile proteins in supporting motile functions and the potential of small ligands as therapeutic drugs. To follow dynamic events in cells and externally triggered changes, we use fluorescence-based microscopy techniques.


Major Scientific Achievements

  • Establishment of a non-crystallographic approach to determine the absolute stereochemistry of FAD and FMN dependent enzymes.
  • Development and first application of molecular genetics tools for targeted gene deletion and gene complementation assays, and recombinant protein production in the model organism Dictyostelium discoideum.
  • Key contributions to the elucidation of the function of nonmuscle myosin-2 in cytokinesis and cell motility.
  • Key contributions to the elucidation of dynamin function, structure, and regulation.
  • Development of protein design and engineering approaches.
  • Engineering of single-polypeptide myosin motors with enhanced stability and motility.
  • Engineered reversal of the direction of movement of myosin motors.
  • Elucidation and experimental verification of the mechanism supporting the backwards directed movement of myosin-6.
  • Elucidation of the mechanisms governing myosin directionality and chemomechanical coupling.
  • Identification and characterization of small molecule modulators of myosin function.
  • First description of a pharmacological chaperone that restores the function of its target protein following heat-inactivation in a time and concentration dependent manner.
  • Elucidation of molecular mechanisms underlying Charcot–Marie–Tooth neuropathy, centronuclear myopathy, familial hypertrophic cardiomyopathy, and nemaline rod myopathy.




Prof. Dr. Dietmar J. Manstein

Institute for Biophysical Chemistry, OE4350
Medizinische Hochschule Hannover
Carl-Neuberg-Str. 1
D-30625 Hannover
Tel: +49-511-532-3700
Fax: +49-511-532-5966

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