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Institut für Genetik
Universität Bonn
Karlrobert-Kreiten-Str. 13
53115 Bonn
Mo-Fr   09:30 - 13:00
Tel.: 0228-73-4210
Fax: 0228-73-4263
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Research interests

Research Unit Prof. Dr. Walter Witke

Head of Research Unit and
Director of Institute
Prof. Dr. Walter Witke
Cell Migration Unit
Phone: 0228-73-4210
Fax: 0228-73-4263


 Prof. Witke




  • Diploma:  Eberhard-Karls University, Tübingen (Biochemistry)
  • Ph.D.:  Ludwig-Maximilians University, Munich (Biochemistry)
  • Postdoctoral Fellow:  Harvard Medical School, Boston, USA
  • Groupleader:  EMBL Mouse Biology Programme, Rome-Monterotondo, Italy
  • since 2009:  Director, Institute of Genetics, Rhein.-Friedrich Wilhelms University, Bonn


Research Interests

  • Role of cell motility in mouse morphogenesis, physiology and disease
  • The cytoskeleton in neuronal migration and synaptic plasticity
  • Actin as a regulator of cell polarity and stem cell division
  • The cytoskeleton as a determinant of local immune responses
  • Regulatory actin binding proteins (Cofilin, ADF, Profilin, WAVE-complex)


Technology and Methods

  • conditional mutagenesis in the mouse
  • targeted control of cell motility in mouse knockout models
  • cell migration studies in cultured cells and tissues
  • primary cell culture, molecular genetics and cell biology


Research Summary

The main interest in our group is to understand the role of the actin cytoskeleton and cell motility in mouse morphogenesis and tissue physiology.
We employ the mouse as a genetic model system to specifically manipulate cell motility in different tissues and cell types. We apply an interdisciplinary approach of molecular genetics, cell biology and biochemistry to understand basic questions of cytoskeletal dynamics during tissue morphogenesis and regeneration, during cell shape changes, cell polarization and cytokinesis. The relevance of cytoskeletal dynamics in physiological processes such as neuronal transmission, local immune responses and metastasis is indisputable, however the control mechanisms and the links of cytoskeletal dynamics to physiological readout  are poorly understood.

Our work has therefore centered around several families of regulatory molecules and complexes, which control the actin cytoskeleton and cell migration. Among these key regulators are the actin binding proteins of the Profilin and Cofilin family - each are represented in mouse and human by a family of genes. Profilin has activities that can  stimulate actin polymerization, while cofilin can sever and depolymerize existing actin filaments. A third group of proteins, the so-called ‘actin nucleator complexes’ represent signaling platforms, which promote the polymerization and remodeling of actin filaments in cells. The pentameric actin nucleating WAVE-complex has recently gained much attention and our group is trying to zoom in on the role of the WAVE-complex mainly in the brain in synaptic transmission and synaptic plasticity.
In the mouse we have recently discovered a central role of the Cofilin family in stem cell fate determination as well as epithelial-mesenchymal transitions (EMT). These findings have interesting implications for the control of tissue homeostasis and the requirements for cancer metastasis. In immune cells Cofilins are on one hand indispensable for chemotaxis and antigen presentation , on the other hand they can promote the entry of HIV-virus into T-cells.

Muscle weakness can be caused by numerous genetic mutations and one of these mutations leading to ‘Nemaline Myopathy’ is localized in the muscle specific cofilin gene. We have modeled the human disease in the mouse and now use this model to decipher the molecular steps that ultimately lead to the muscle defects. A better understanding of the mechanism is essential in developing strategies to ameliorate the phenotypic consequences.   

In the brain, cell motility is crucial for proper development as well as for normal physiology. For example, we could show that in the mouse Lissencephaly, a severe form of mental retardation, can result from mutation of cofilin.
Mutation of cofilin, or profilin in postnatal brain directly affects complex behavior and synaptic plasticity such as learning and memory. Interestingly, cofilin is specifically required for associative learning but not for exploratory learning. In simple words, without cofilin we will memorize how to drive a car, but we will not be able to adjust our driving style even after receiving hundreds of speeding tickets.
Mutation of Profilin leads to very different alterations of behaviour. Mutant mice have excessive release of neurotransmitter in the synapse and they show a phenotype that very much resembles the symptoms seen in autism.   

Current and future projects in our unit focus on mechanisms of actin dynamics in synaptic plasticity, on the polarity of stem cell division, on local immune responses and mechanisms of metastasis. Conditional mouse mutants, biochemical approaches and primary cell and organ cultures are employed to gain insights into the fascinating world of cell migration. 

The ongoing projects are supported by individual DFG (Deutsche Forschungsgemeinschaft) grants, through the participation in the local research initiative SFB704 (Molecular mechanisms and chemical modulation of local immune regulation) and the priority research initiative SPP 1464 (Principles and evolution of actin-nucleator complexes).

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