Skip to content

Dietmar J. Manstein

  • Dr. rer.nat.
  • Director Research Unit for Laser Microscopy
  • Medizinische Hochschule Hannover
  • 42h-indexImpact measure calculated using publication and citation counts. Updated daily.
  • 6094CitationsNumber of citations received by Dietmar J.'s publications. Updated daily.

About

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.

SCIENTIFIC ACHIEVEMENTS • Total synthesis of FAD and FMN analogues and their application for probing stereo-specificities of flavin cofactors in enzymatic reactions. • Pioneering work on the molecular genetic manipulation of the model organism Dictyostelium discoideum. • Key contributions to the development and application of molecular genetics, transient kinetics, and hybrid structural biology approaches for the elucidation of myosin and dynamin function, structure, and regulation. • Establishment of the first recombinant expression system for the production of functional myosin motors. • Application of protein engineering approaches leading to the elucidation of the fundamental principles governing myosin directionality and chemomechanical coupling. • Engineering of single-polypeptide myosin motors with enhanced stability and motility for use in biohybrid devices. • Structural characterization of the actomyosin complexes produced in Dictyostelium and human cells and elucidation of their involvement in cytokinesis and cell motility. • Structure-based identification of multi-site allostery in the myosin motor domain and characterization of several class-specific small molecule modulators of cytoskeletal myosins. • First description of a pharmacological chaperone for cardiac beta-myosin. Addition of the small molecule to the functionally impaired target protein leads to full restoration of myosin motor activity in a time and concentration dependent manner. • Elucidation of the function of cytoskeletal tropomyosins in controlling the motor activity and dynamic behavior of myosins in an isoform-specific manner.

Editorships

FEBS OpenBio

FEBS OpenBio

FEBS OpenBio

Associate Editor

2011 - Present

FEBS Letters

FEBS Letters

FEBS Letters

Editor

2008 - Present

Professional experience

Director Research Unit for Laser Microscopy

Medizinische Hochschule Hannover

January 2005 - Present

Director - Structural Biochemistry

Medizinische Hochschule Hannover

January 2003 - Present

Director - Biophysical Chemistry

Medizinische Hochschule Hannover

October 2002 - Present

Deputy Director

Centre for Structural Systems Biology, Hamburg

December 2017 - December 2019(2 years)

Group leader (C3)

Max-Planck-Institut für Medizinische Forschung

April 1996 - September 2002(6 years)

Visiting Professor

NICT, Japan

September 1999 - December 1999(3 months)

Visiting Professor

National Institute for Advanced Interdisciplinary Research Tsukuba Tsukuba, Japan

October 1996

Visiting Professor

NICT, Japan

September 1996 - October 1996(a month)

Group Leader

National Institute for Medical Research

April 1990 - March 1996(6 years)

Postdoctoral Researcher

Stanford University School of Medicine

April 1987 - March 1990(3 years)

Postdoctoral Researcher

Max-Planck-Institut für Medizinische Forschung

July 1986 - March 1987(8 months)

Visiting Research Fellow

University of Michigan Medical School

June 1986 - November 1986(5 months)

Visiting Research Fellow

University of Michigan Medical School

June 1985 - November 1985(5 months)

Visiting Research Fellow

European Molecular Biology Laboratory

June 1983 - December 1983(6 months)

Education

Dr. rer.nat

Ruprecht Karls Universitat Heidelberg

January 1984 - January 1986(2 years)

Diploma Biochemistry

Leibniz Universität Hannover

October 1978 - December 1983(5 years)

Other profiles

Personal website

https://www.mhh.de/bpc/dietmar-manstein

Co-authors (398)