Basic Mechanisms of Tissue Formation (2007-2011)

Objectives

The goal of our studies is to understand at the molecular level protein interactions that couples chemical and mechanical signals to the regulation of diverse cellular processes such as cell proliferation, cell shape, migration, and differentiation. We therefore dissect the structure and cellular function of receptors (e.g. NK-receptor), signaling molecules (cyclin-dependent kinases and mitogen-activated kinases ), and downstream effectors like molecular motors (e.g. myosins and kinesins).

Research Focus

Structural investigation of protein interaction by high-throughput X-ray crystallography and molecular modeling (in silico methods) is at the heart of our research activities, which allows the prediction and identification of individual protein residues or regions implicated in the interactions with other proteins, peptides, and ligands. Structure-function relationship analysis by pre-steady state kinetic characterization and thermodynamic characterization by ultrasensitive calorimetric measurements complete our understanding of how specific protein functions are achieved at the molecular level. This holistic approach shall reveal new alternatives for modification of signaling and motor protein associated cellular functions and pathways and will supply us with tools for studying and modulating processes implicated in embryogenesis, and pathological abnormalities including tumor genesis, as well as neurosensory and cardiac disorders. Another objective is to targeted design and to synthesize of molecules that will bind with high affinity and selectivity to isoform-specific protein binding sites, thus modifying protein function in a desirable fashion.

Collaborations

  • Kinaris Biomedicals GmbH, Investigation of novel allosteric binding site in the myosin motor domain
  • Dr. I. Gruh, Prof. U. Martin, Hannover Medical School, REBIRTH, JRG Myocardial Tissue-Engineering, Development and application of 2D/3D cellular assays for drug development in cardiac diseases
  • Prof. M. Gaestel, Hannover Medical School, Institute for Physiological Chemistry, REBIRTH, Structural determination of MK5 and ERK 3/ERK 4, proteins of the MAPK (mitogen-activated protein kinases) signaling pathway
  • Prof. N. Malek, Hannover Medical School, REBIRTH, W2 Proliferation, Structural and functional determination of p27-inhibitor on CDK2/ cycA / cycE cycle with tissue regenerating effect

Teaching

  • Lecture and practical course Structural Biology for students of biochemistry

Equipment and Service Facilities

[Please find a list of all available equipment here]

Publications

[Please find the publications of this workgroup here]

Staff

Reubold, Thomas Dr. Reubold.Thomas (at) mh-hannover.de
Hennig, Anne Hennig.Anne (at) mh-hannover.de
Patronov, Atanas Patronov.Atanas (at) mh-hannover.de
Preller, Matthias Preller.Matthias (at) mh-hannover.de
Weninger, Gunnar Weninger.Gunnar (at) mh-hannover.de
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