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.
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.
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
Prof. Dr. Dietmar J. Manstein
Institute for Biophysical Chemistry, OE4350
Medizinische Hochschule Hannover