Division of Biophysics of Macromolecules

Prof. Dr. Jörg Langowski

Computer model of the 30 nm ch...
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Gene activity is not determined by the DNA sequence alone, but also by its three-dimensional organization in the cell: DNA and chromatin global structure plays a crucial role in the regulation of many processes, such as cell differentiation or carcinogenesis. We study the three-dimensional structure and dynamics of the genome in normal and tumor cells and describe it by quantitative models taken from physics and mathematics. This will help us understand the connection between genome structure and normal or pathological states of the cell. We study long-range interactions in genomic DNA, the structure of nucleosomes and chromatin fiber, and the organization of chromosome territories in the living cell nucleus. The experiments are supplemented by advanced computer simulation techniques that describe the organization of DNA and chromatin as a flexible polymer.
All these studies require advanced biophysical methods. A special emphasis in our group is on single-molecule techniques (fluorescence correlation spectroscopy, single pair FRET, scanning force microscopy), and advanced imaging (single plane illumination microscopy). Furthermore, we use light and neutron scattering, analytical ultracentrifugation, absorption and fluorescence spectroscopy, and stopped flow kinetics. Our methodology is actively used in collaborations for characterizing protein-protein and protein-DNA interactions, as well as for intermediate filament proteins.

FUTURE OUTLOOK
In the future, we shall follow three major lines of research:

1. the role of histone tails and their modifications in chromatin packaging, using single molecule FRET to characterize structural transitions in nucleosomes;
2. the dynamics of protein transport in the cell nucleus, using our newly developed single plane illumination microscopy with ultra-fast detection;
3. the dynamics of assembly of intermediate filament (IF) proteins, the biophysical characterization of their structure and flexibility, and their role in nuclear architecture.

Our computer simulation activities range from atomic-detail molecular dynamics of proteins and DNA to coarse-grained models of the genome architecture in entire cell nuclei. This theoretical aspect will always form an important complement to our experimental research. The ultimate goal is to design a physical model of the entire cell in time and space, which can contribute to the understanding of cancer development and to its therapy. Our research shall be a step on the way there.

Website of the Division

Contact

Prof. Dr. Jörg Langowski
Biophysics of Macromolecules (B040)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 6221 42 3390
Fax: +49 6221 42 3391

Selected Publications

  • Pernus A. and Langowski J. (2015). Imaging Fos-Jun transcription factor mobility and interaction in live cells by single plane illumination-fluorescence cross correlation spectroscopy. PLoS One, 10(4):e0123070
  • Erler J. et al. (2014). The role of histone tails in the nucleosome: A computational study. Biophysical Journal, 107(12), 2911-2922.
  • Krieger J.W. et al. (2014). Dual-Color Fluorescence Cross-Correlation Spectroscopy on a Single Plane Illumination Microscope (SPIM-FCCS). Opt Express, 22(3), 2358-2375
  • Böhm V. et al. (2010). Nucleosomal DNA accessibility governed by the dimer/tetramer interface. Nucleic Acids Research, 39(8), 3093–3102.
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