Experimental Biophysics 

 

 

In cellular systems the main data storage for various functions is the cell nucleus containing the DNA. Beyond the sequence of DNA molecules, the three dimensional spatial organization of the micro- and nano-architecture plays an important role for the control of the complex system cell. In addition, in sequence data characteristic patterns can be found which lead to the expectation that the organization may not be random. These patterns are well conserved along phylogenetic lines during evolution.

Cellular data stored in the nucleus induce complex functional cascades and regulatory cycles of cellular proteins. These functional cycles are often displayed on the cellular membrane by appropriate signal molecules which allows cellular systems to communicate with their natural environment. Genes and nucleotide sequences in the nucleus and proteins and receptors on the membrane can be understood as corresponding endpoints of complex functional cascades of a cellular system. Molecular-chemically or physically triggered modification on one or the other side are resulting in spatial re-arrangements and compaction changes of DNA or receptors and proteins, respectively. The dynamics and charaxteristics can be investigated with novel techniques of super-resolution microscopy and nano-labelling.

The research group "€œExperimental Biophysics" is working on questions of the organization of bio-molecules and sub-cellular units in cellular systems considering biomedical applications and medical diagnostics. By means of fluorescence microscopy and super-resolution microscopy basic research as well as applied research is done in the field of radiation-biophysics and tumour medicine.

For the investigation of different kinds of information being contained by the cell nucleus chromatin, DNA data bases are analyzed and compared for specific pattern formations. Based on these analyses fundamental results for the chromatin organization can be obtained and also sequences for the design of specific oligonucleotide nano-probes for for microscopy are determined.

Such molecular labelling techniques allow the investigation of structures and organization principles in 3D-conserved cell nuclei. Cells are not only exposed to externeal stimuli like ionizing radiation, molecular ligands or therapeutic antibodies but also to special geometric physical boundary conditions which allow to mimic tissue equivalent cell ensembles.

Research on intrisic information being archived and processed in cells results in priciple investigations of organization and use of archives in a broader sense as being discussed interdiciplinarily between sciences and humanities.

Beyond this research and based on theoretical considerations, conditions are studied being relevant for the development of molecular pre-requisits which may be possible for life also under extreme conditions.

In the research group cellular and sub-cellular systems of organization are studied on different levels of complexicity and unter different boundary conditions. Theoretical and experimental work contribute to a coherent biophysical image of cellular and sub-cellular systems.The work can be subdivided in following projects:

  • Systematic analysis of sequence patterns and frquencies as well as positions of k-mers along the phylogenetic tree

  • COMBO-FISH: Development of oligonucleotide combinations for specific labelling of genome targets

  • Radiation biophysics: Investigations of the 3D micro- and nano-architecture of the cell nucleus and their modifications after exposure to ionizing radiation

  • Radiation biophysics: Specific incorporation of nano-particles (nano-gold) in cells and cell nuclei and mechanisms of interaction with ionizing radiation

  • Investigations of the 3D nano-architecture of receptor clusters and proteins of the cell membrane after exposure to ionizing radiation, molecular stimuli, and chemo-therapeutic agents

  • Preparation of artifical cell geometries and arrangements to mimic tissue equivalents for the investigation or orchestrated cell response mechanisms

  • Development of concepts for sustainable archivation of biophysical data

  • Astrobiophysics: Physical aspects on the development of living systems

 

The research is supported by:

UNDER CONSTRUCTION

Contact:

Prof. Dr. Michael Hausmann

Kirchhoff-Institute for Physics
Im Neuenheimer Feld 227
69120 Heidelberg
Germany
 
For 20 years, Michael Hausmann was council member of the "Deutschen Gesellschaft für Biologische Strahlenforschung (DeGBS)"(German Society for Biological Radiation Research).
Publikationen/Publications
Gesamtverzeichnis bis einschließlich 2020 /
List of publications until 2020

2023
  1. Sievers A, Sauer L, Bisch M, Sprengel J, Hausmann M, Hildenbrand G (2023) Moderation of structural DNA properties by coupled dinucleotide contents in eukaryotes. Genes 14, 755. https://doi.org/10.3390/genes14030755
  2. Weidner J, Neitzel C, Gote M, Deck J, Küntzelmann K, Pilarczyk G, Falk M, Hausmann M (2023) Advanced image-free analysis of the nano-organization of chromatin and other biomolecules by Single Molecule Localization Microscopy (SMLM). Computational and Structural Biotechnology Journal 21: 2018-2034. https://doi.org/10.1016/j.csbj.2023.03.009
  3. Erenpreisa J, Giuliani A, Yoshikawa K, Falk M, Hildenbrand G, Salmina K, Freivalds T, Vainshelbaum N, Weidner J, Sievers A, Pilarczyk G, Hausmann M (2023)Spatial-temporal genome regulation in stress-response and cell-fate change. Int J Mol Sci 24: 2658. https://doi.org/10.3390/ijms24032658
  4. Chapman KB, Filipsky F, Peschke N, Gelléri M, Weinhardt V, Braun A, Hausmann M, Cremer C (2023) A comprehensive method to study the DNA’s association with lamin and chromatin compaction in intact cell nuclei at super resolution. Nanoscale 15: 742. https://doi.org/10.1039/D2NR02684H
2022
  1. Hausmann M, Schmitt E (2022) Combinatorial Oligonucleotide FISH (COMBO-FISH): Computer designed probe sets for microscopy research of chromatin in cell nuclei. In: "Oligonucleotides - Overview and Applications",Intech-Open, Rijeka, DOI: http://dx.doi.org/10.5772/intechopen.108551
  2. Hausmann, M., Hildenbrand, G., Pilarczyk, G. (2022). Networks and Islands of Genome Nano-architecture and Their Potential Relevance for Radiation Biology. In: Kloc, M., Kubiak, J.Z. (eds) Nuclear, Chromosomal, and Genomic Architecture in Biology and Medicine. Results and Problems in Cell Differentiation, vol 70. Springer, Cham, pp.3-34. https://doi.org/10.1007/978-3-031-06573-6_1
  3. Rodener D, Schäfer M, Hausmann M, Hildenbrand G (2022) Assessing the potential for liquid solvents from X-ray sources: considerations on bodies orbiting active galactic nuclei. Galaxis 10: 101. https://doi.org/10.3390/galaxies10050101
  4. Hildenbrand G, Paschek K, Schäfer M, Hausmann M (2022) Cryovolcanism in the solar system and beyond: Considerations on energy sources, geological aspects, and astrobiological perspectives. In: “Astronomy” (Chemin Y H, ed.)Intech-Open, Rijeka,Available: https://www.intechopen.com/online-first/81911;doi: 10.5772/intechopen.105067
  5. Chakraborty S, Singh M, Pandita R, Singh V, Lo C, Leonard F, Horikoshi N, Moros E, Guha D, Hunt C, Makhijani K, Chau E, Ahmed K, Sethi P, Charaka V, Godin B, Makhijani K, Scherthan H, Deck J, Hausmann M, Mushtaq A, Altaf M, Ramos K, Bhat K, Taneja N, Das C, Pandita T (2022) Heat-induced SIRT1-mediated H4K16ac deacetylation impairs resection and SMARCAD1 recruitment to double strand breaks. iScience 25, 104142.
  6. Rodener D, Hausmann M, Hildenbrand G (2022) Assessing the potential for liquid solvents from X-ray sources: considerations on bodies orbiting AGN. Preprint at arXiv:2202.04562 [astro-ph.EP]
  7. Chakraborty S, Singh M, Pandita R, Singh V, Lo C, Leonard F, Horikoshi N, Moros E, Guha D, Hunt C, Makhijani K, Chau E, Ahmed K, Sethi P, Charaka V, Godin B, Makhijani K, Scherthan H, Deck J, Hausmann M, Mushtaq A, Altaf M, Ramos K, Bhat K, Taneja N, Das C, Pandita T (2022) Heat-induced SIRT1-mediated H4K16ac deacetylation impairs resection and SMARCAD1 recruitment to double strand breaks. Preprint at SSRN: https://ssrn.com/abstract=4007582 or http://dx.doi.org/10.2139/ssrn.4007582
  8. Dobešová L, Gier T, Kopečná O, Pagáčová E, Vičar T, Bestvater F, Toufar J, Bačíková A, Kopel P, Fedr R, Hildenbrand G, Falková I, Falk M, Hausmann M (2022)Incorporation of low concentrations of gold nanoparticles: Complex effects on radiation response and fate of cancer cells. Pharmaceutics 14: 166. https://doi.org/10.3390/pharmaceutics14010166
2021
  1. Hahn H, Neitzel C, Kopecná O, Heermann DW, Falk M, Hausmann M (2021) Topological analysis of γH2AX and MRE11 clusters detected by localization microscopy during X-ray-induced DNA double-strand break repair. Cancers 13, 5561. https://doi.org/10.3390/cancers13215561
  2. Sievers A, Sauer L,  Hausmann M, Hildenbrand G (2021) Eukaryotic genomes show strong evolutionary conservation of k-mer composition and correlation contributions between introns and intergenic regions. Genes 12, 1571.
    https://doi.org/10.3390/genes12101571
  3. Hausmann M, Neitzel C, Hahn H, Winter R, Falkova I, Heermann DW, Pilarczyk G, Hildenbrand G, Scherthan H, Falk M (2021) Space and time in the universe of the cell nucleus after ionizing radiation attacks: a comparison of cancer and non-cancer cell response. (presented on 1st Int. Elec. Conf. Cancers: Exploiting Cancer Vulnerability by Targeting the DNA Damage Response) Med. Sci. Forum 3: 15. https:// doi.org/10.3390/IECC2021-09219
  4. Paschek K, Roßmann A, Hausmann M, Hildenbrand G (2021) Analysis of tidal accelerations in the solar system and in extrasolar planetary systems. Appl. Sci. 11, 8624.https://doi.org/10.3390/app11188624
  5. Bartosova M, Ridinger D, Marinovic I, Heigwer J, Zhang C, Levai E, Westhoff JH, Schaefer F, Terjung S, Hildenbrand G, Krunic D, Bestvater F, Hausmann M, Schmitt CP,  Zarogiannis SG (2021) An experimental workflow for studying barrier integrity, per-meability, and tight junction composition and localization in a single endothelial cell monolayer: Proof of concept. Int. J. Mol. Sci. 22: 8178.
    https://doi.org/10.3390/ijms22158178
  6. Paschek K, Roßmann A, Hausmann M, Hildenbrand G (2021) Analysis of tidal accelerations in the solar system and in extrasolar planetary systems. Preprints 2021: 2021070408. doi: 10.20944/preprints202107.0408.v1
  7. Hausmann M,Neitzel C, Bobkova E, Nagel D, Hofmann A, Chramko T, Smirnova E, Kopecná O, Pagácová E, Boreyko A, Krasavin E, Falkova I, Heermann DW, Pilarczyk G, Hildenbrand G, Bestvater F, Falk M (second publication 2021) Single Molecule Localization Microscopy analyses of DNA-repair foci and clusters detected along particle damage tracks. In: Applied Nuclear Physics at Accelerators (Durante M, Patera V, Prezado Y, eds.) Lausanne: Frontiers Media SA. doi: 10.3389/978-2-88971-039-3: 363-377
  8. Erenpreisa J, Krigerts J, Salmina K, Gerashchenko BI, Freivalds T, Kurg R, Krufczik M, Winter R, Zayakin P, Hausmann M, Giuliani A (2021) Heterochromatin networks: topology, dynamics, and function (a working hypothesis). Cells 10, 1582. https://doi.org/10.3390/cells10071582
  9. Hausmann M, Falk M, Neitzel C, Hofmann A, Biswas A, Gier T, Falkova I, Heermann DW, Hildenbrand G (2021)Elucidation of the clustered nano-architecture of radiation-induced DNA damage sites and surrounding chromatin in cancer cells: A Single Molecule Localization Microscopy approach. Int. J. Mol. Sci. 22: 3636 doi.org/10.3390/ijms22073636
  10. Krigerts J, Salmina K, Freivalds T, Zayakin P, Rumnieks F, Inashkina I, Giuliani A,  Hausmann M, Erenpreisa J (2021) Differentiating breast cancer cells reveal early large-scale genome regulation by pericentric domains. Biophys. J. 120: 711-724; https://doi.org/10.1016/j.bpj.2021.01.002
  11. Lee J-H, Hausmann M (2021) Super-resolution radiation biology: From bio-dosimetry towards nano-studies of DNA repair mechanisms. In: “DNA-Repair” (BehzadiP, ed.). Intech-Open, Rijeka, ISBN 978-1-83881-094-8: DOI: http://dx.doi.org/10.5772/ intechopen.95597
  12. Falk M, Hausmann M (2021) A paradigm revolution or just better resolution - will newly emerging superresolution techniques identify chromatin architecture as a key factor in radiation-induced DNA damage and repair regulation?. Cancers 13, 18. https://dx.doi.org/10.3390/cancers13010018
2020
  1. Falk M, Hausmann M (2020). Nové poznatky o poškození bunek a chromatinu (DNA) ruznými druhy ionizujícího zárení v ére pokrocilé optické mikroskopie a nanoskopie [New discoveries on cell and chromatin damage by different types of ionizing radiation in the era of advanced optical microscopy and nanoscopy]. Casopis lékaru ceských [Cas Lék ces. = Journal Czech Physicians]159: 286-297
  2. Hausmann M,Neitzel C, Bobkova E, Nagel D, Hofmann A, Chramko T, Smirnova E, Kope?ná O, Pagá?ová E, Boreyko A, Krasavin E, Falkova I, Heermann DW, Pilarczyk G, Hildenbrand G, Bestvater F, Falk M (2020) Single Molecule Localization Microscopy analyses of DNA-repair foci and clusters detected along particle damage tracks.