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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 "€śExperimental Biophysics"ť 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:
Prof. Dr. Michael Hausmann
Kirchhoff-Institute for Physics
Im Neuenheimer Feld 227
List of publications
- 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
- 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. Front. Phys. 8: 578662; doi: 10.3389/fphy.2020.578662
- Falk M, Wolinsky M, Veldwijk MR, Hildenbrand G, Hausmann M (2020) Gold nanoparticle enhanced radiosensitivity of cells: Considerations and contradictions from model systems and basic investigations of cell damaging for radiation therapy. In: “Nanoparticle Enhanced Radiation Therapy – Principles, Methods and Applications” (eds. Sajo E, Zygmanski P),IOP Publishing Ltd 2020, pp. 10-1 – 10-25; https://doi.org/10.1088/978-0-7503-2396-3ch10
Hausmann M, Pilarczyk G, Maus E, Hesser J, Hildenbrand G (2020) Super-Resolution Microscopy of nanogold-labelling. In: “Nanoparticle Enhanced Radiation Therapy – Principles, Methods and Applications” (eds. Sajo E, Zygmanski P),IOP Publishing Ltd 2020, pp. 11-1 – 11-8;
- Bartosova M, Herzog R, Ridinger D, Levai E, Jenei H, Zhang C, González Mateo GT, Marinovic I, Hackert T, Bestvater F, Hausmann M, López Cabrera M, Kratochwill K, Zarogiannis SG, Schmitt CP (2020) Alanyl-glutamine restores tight junction organization after disruption by a conventional peritoneal dialysis fluid. Biomolecules 10: 1178; doi: 10.3390/biom10081178
- Hausmann M, Lee J-H, Hildenbrand G (2020) 3D DNA FISH for analyses of chromatin-nuclear architecture. In: “Epigenetics Methods”, Vol 18 (ed. Tollefsbol T) Elsevier Academic Press: pp 399-418; doi.org/10.1016/B978-0-12-819414-0.00020-3
- Hildenbrand G, Weinschenk S, Hausmann M (2020) Moderne Physik, biologische Systeme und komplementäre Medizin. In: Handbuch Neuraltherapie, 2. Auflage (Ed.: Weinschenk S), Georg Thieme Verlag, Stuttgart: pp. 159-167
Hausmann M, Lee J-H, Sievers A, Krufczik M, Hildenbrand G (2020) COMBinatorial Oligonucleotide FISH (COMBO-FISH) with uniquely binding repetitive DNA probes. The Nucleus (ed. Hancock R), Methods in Molecular Biology. 2175: 65-77;
- Krigerts J, Salmina K, Freivalds T, Rumnieks F, Inashkina I, Zayakin P, Hausmann M, Erenpreisa J (2020) Early critical phase transitions of pericentromere-associated domains in MCF-7 breast cancer cells committed to differentiation by heregulin. Preprints 2020: 2020050248; doi: 10.20944/preprints202005.0248.v1
- Scherthan H, Lee J-H, Maus E, Schumann S, Muhtadi R, Chojowski R, Port M, Lassmann M, Bestvater F, Hausmann M (2019) Nanostructure of clustered DNA damage in leukocytes after in-solution irradiation with the alpha emitter Ra-223. Cancers 11: 1877; doi:10.3390/cancers11121877
- Salmina K, Gerashchenko BI, Hausmann M, Vainshelbaum NM, Zayakin P, Erenpreiss J, Freivalds T, Cragg MS, Erenpreisa J (2019) When three isn't a crowd: A digyny concept for treatment-resistant, near-triploid human cancers. Genes 10(7): 551; https://doi.org/10.3390/genes10070551
- Pilarczyk G., Papenfuß F, Bestvater F, Hausmann M (2019) Spatial arrangements of Connexin43 in cancer related cells and re-arrangements under treatment conditions: Investigations on the nano-scale by super-resolution localization light microscopy. Cancers 11: 301. doi:10.3390/cancers11030301
- Lee J-H, Laure Djikimi Tchetgna F, Krufczik M, Schmitt E, Cremer C, Bestvater F, Hausmann M (2019) COMBO-FISH: A versatile tool beyond standard FISH to study chromatin organization by fluorescence light microscopy. OBM Genetics 3(1): doi:10.21926/obm.genet.1901064
- Pagácová E, Štefancíková L, Schmidt-Kaler F, Hildenbrand G, Vicar T, Depeš D, Lee J-H, Bestvater F, Lacombe S, Porcel E, Roux S, Wenz F, Kopecná O, Falková I, Hausmann M, Falk M (2019) Challenges and contradictions of metal nano-particle applications for radio-sensitivity enhancement in cancer therapy. Int. J. Molec. Sci. 20: 588. doi:10.3390/ijms20030588