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
- Hausmann M, Wagner E, Lee J-H, Schrock G, Schaufler W, Krufczik M, Papenfuß F, Port M, Bestvater F, Scherthan H (2018) Super-resolution microscopy of radiation-induced histone H2AX phosphorylation in relation to H3K9-trimethylation in HeLa cells. Nanoscale 10: 4320-4331; doi:10.1039/C7NR08145F
- Eryilmaz M, Schmitt E, Krufczik M, Theda F, Lee J-H, Cremer C, Bestvater F, Schaufler W, Hausmann M, Hildenbrand G (2018) Localization microscopy analyses of MRE11 clusters in 3D-conserved cell nuclei of different cell lines. Cancers 10: 25; doi:10.3390/cancers10010025
- Hildenbrand G, Metzler P, Pilarczyk G, Bobu V, Kriz W, Hosser H, Fleckenstein J, Krufczik M, Bestvater F, Wenz F, Hausmann M (2018) Dose enhancement effects of gold nanoparticles specifically targeting RNA in breast cancer cells. PLoS ONE 13(1): e0190183. https://doi.org/10.1371/journal.pone.0190183
- Eberle JP, Rapp A, Krufczik M, Eryilmaz M, Gunkel M, Erfle H, Hausmann M (2017) Super-resolution microscopy techniques and their potential for applications in radiation biophysics. In: “Super-resolution Microscopy – Methods and Protocols” (Erfle H, ed.) Meth. Molec. Biol. 1663: 1-13
- Hausmann M, Ilic N, Pilarczyk G, Lee J-H, Logeswaran A, Borroni AP, Krufczik M, Theda F, Waltrich N, Bestvater F, Hildenbrand G, Cremer C, Blank M (2017) Challenges for super-resolution localization microscopy and biomolecular fluorescent nano-probing in cancer research. Int. J. Mol. Sci. 18: 2066; doi:10.3390/ijms18102066
- Bach M, Savini C, Krufczik M, Cremer C, Rösl F, Hausmann M (2017) Super-resolution localization microscopy of γ-H2AX and heterochromatin after folate deficiency. Int. J. Mol. Sci. 18: 1726; doi:10.3390/ijms18081726
- Krufczik M, Sievers A, Hausmann A, Lee Jin-Ho, Hildenbrand G, Schaufler W, Hausmann M (2017) Combining low temperature fluorescence DNA-hybridization, immunostaining, and super-resolution localization microscopy for nano-structure analysis of ALU elements and their influence on chromatin structure. Int J Mol Sci 18: 1005; doi:10.3390/ijms18051005
Sievers A, Bosiek K, Bisch M, Dreessen C, Riedel J, Froß P, Hausmann M,
Hildenbrand G (2017)Kmer content, correlation and position analysis of genome DNA sequences for identification of function and evolutionary features. Genes 8: 122;doi:10.3390/genes8040122
- Ngwa W, Boateng F, Kumar R, Irvine DJ, Formenti S, Ngoma T, Herskind C, Veldwijk MR, Hildenbrand GL, Hausmann M, Wenz F, Hesser J (2017) Critical review: Smart radiotherapy biomaterials. Int J Radiation Oncol Biol Phys 97: 624-637 (http://dx.doi.org/10.1016/j.ijrobp.2016.10.034)
- Pilarczyk G, Nesnidal I, Gunkel M, Bach M, Bestvater F, Hausmann M (2017) Localisation microscopy of breast epithelial ErbB-2 receptors and gap junctions: Trafficking after gamma-irradiation, Neuregulin-1b and Herceptin application. Int J Mol Sci 18: 362; doi:10.3390/ijms18020362
- Pilarczyk G, Raulf A, Gunkel M, Fleischmann BK, Lemor R, Hausmann M (2016) Tissue mimicking geometrical constraints stimulate tissue-like constitution and activity of mouse neonatal and human induced pluripotent stem cell-derived cardiac myocytes. J. Funct. Biomat. 7(1), 1: doi:10.3390/jfb7010001
- Moser F, Hildenbrand G, Müller P, Al Saroori A, Biswas A, Bach M, Wenz F, Cremer C, Burger N, Veldwijk M, Hausmann M (2016) Cellular uptake of gold nanoparticles and their behavior as labels for localization microscopy. Biophys J 110: 947-953
- Bosiek K, Hausmann M, Hildenbrand G (2016) Perspectives on comets, comet-like asteroids, and their predisposition to provide an environment that is friendly to life. Astrobiology 16(4): 311-323 (doi:10.1089/ast.2015.1354)
- Müller P, Rößler J, Schwarz-Finsterle J, Schmitt E, Hausmann M (2016) PNA-COMBO-FISH: From combinatorial probe design in silico to vitality compatible, specific labelling of gene targets in cell nuclei. Exp Cell Res 345: 51-59
- Boyd PS, Struve N, Bach M, Eberle JP, Gote M, Schock F, Cremer C, Kriegs M, HausmannM (2016) Clustered localization of EGFRvIII in glioblastoma cells as detected by high precision localization microscopy. Nanoscale: DOI: 10.1039/c6nr05880a
Aschenbrenner KP, Butzek S, Guthier CV, Krufczik M, Hausmann M, Bestvater F, Hesser J (2016) Compressed sensing denoising for segmentation of localization microscopy data. IEEE Int. Conf. Comput. Intelligence Bioinf. Comput. Biol. (CIBCB 2016, 5.- 7. 10. 2016, Chiang Mai, Thailand): 1-5
- Zhang Y, Máté G, Müller P, Hillebrandt S, Krufczik M, Bach M, Kaufmann R, Hausmann M, Heermann DW (2015) Radiation induced chromatin conformation changes analysed by fluorescent localization microscopy, statistical physics, and graph theory. PLoS ONE 10: e0128555. doi:10.1371/journal.prone.0128555
- Stuhlmüller M, Schwarz-Finsterle J, Fey E, Lux J, Bach M, Cremer C, Hinderhofer K, Hausmann M, Hildenbrand G (2015) In situ optical sequencing and nano-structure analysis of a trinucleotide expansion region by localization microscopy after specific COMBO-FISH labelling. Nanoscale 7: 17938-17946 (DOI: 10.1039/C5NR04141D)
- Stuhlmüller M, Hausmann M (2015) Selection of COMBO-FISH probes for multi-purpose applications. J. Theor. Comput. Sci. 2: 131-132 (DOI:10.4172/2376-130X. 1000131)
- Bigge K, ?ermák D, Schubert V, Guerin EA, Blessenohl MA, Passenberg F, Bach M, Hausmann M, Hildenbrand G (2015) FLASH for biological dosimetry experiments – A Bexus 16 project. Proc 22nd ESA Symp Europ Rocket and Balloon Programmes and Related Research, Tromsö, 7. – 12. 06. 2015, ESA Sp-730, September 2015: 251 – 258
Boyd PS, Struve N, Bach M, Eberle JP, Gote M, Schock F, Cremer C, Kriegs M, HausmannM (2016) Clustered localization of EGFRvIII in glioblastoma cells as detected by high precision localization microscopy. Nanoscale: DOI: 10.1039/c6nr05880a
- Burger N, Biswas A, Barzan D, Kirchner A, Hosser H, Hausmann M, Hildenbrand G, Herskind C, Wenz F, Veldwijk MR (2014) A method for the efficient cellular uptake and retention of small modified gold nanoparticles for the radiosensitization of cells. Nanomedicine 10: 1365-1373 (doi: 10.1016/j.nano.2014.03.011)
- Grunzke R, Hesser J, Starek J, Kepper N, Gesing S, Hardt M, Hartmann V, Kindermann S, Potthoff J, Hausmann M, Müller-Pfefferkorn R, Jäkel R (2014) Device-driven metadate management solution for scientific big data use cases. 22nd Euromicro Int. Conf. Parallel, Distributed, and Network-Based Processing (PDP 2014), February 2014, Turin, Italy. IEEE Comp. Soc. Proc. PDP 2014: 317 – 321 (doi: 10.1109/PDP.2014. 119)
- Falk M, Hausmann M, Lukášová E,Biswas A, Hildenbrand G, Davídková M, Krasavin E, Kleibl Z, Falková I, Jeková L, Štefaníková L, Ševík J, Hofer M, Baíková A, Matula P, Boreyko A, Vachelová J, Michaelidisová A, Kozubek S (2014) Giving OMICS spatiotemporal dimensions by challenging microscopy: From functional networks to structural organization of cell nuclei elucidating mechanisms of complex radiation damage response and chromatin repair – PART A (Radiomics). Crit. Rev. Eukaryot. Gene Express. 24: 205-223
- Falk M, Hausmann M, Lukášová E, Biswas A, Hildenbrand G, Davídková M, Krasavin E, Kleibl Z, Falková I, Jeková L, Štefaníková L, Ševík J, Hofer M, Baíková A, Matula P, Boreyko A, Vachelová J, Michaelidisová A, Kozubek S (2014) Giving OMICS spatiotemporal dimensions by challenging microscopy: From functional networks to structural organization of cell nuclei elucidating mechanisms of complex radiation damage response and chromatin repair – PART B (Structuromics) . Crit. Rev. Eukaryot. Gene Express. 24: 225-247
- Müller P, Lemmermann NA, Kaufmann R, Gunkel M, Paech D, Hildenbrand G, Holtappels R, Cremer C, Hausmann M (2014) Spatial distribution andstructural arrangement of a murine cytomegalovirus glycoprotein detected by SPDM localization microscopy (mit Titelbild). Histochem. Cell Biol. 142: 61-67
Cremer C, Kaufmann R, Gunkel M, Polanski F, Müller P, Dierkes R, Degenhard S, Wege C, Hausmann M, Birk U (2014) Application perspectives of localization microscopy in virology. Histochem. Cell Biol. 142: 43-59
- Zeller D, Kepper N, Hausmann M, Schmitt E (2013) Sequential and structural biophysical aspects of combinatorial oligo-FISH in Her2/neu breast cancer diagnostics. IFMBE Proc. 38: 82-85
- Hausmann M, Müller P, Kaufmann R, Cremer C (2013) Entering the nano-cosmos of the cell by means of spatial position determination microscopy (SPDM): Implications for medical diagnostics and radiation research. IFMBE Proc. 38: 93-95
- Schwarz-Finsterle J, Scherthan H, Huna A, González P, Müller P, Schmitt E, Erenpreisa J, Hausmann M (2013) Volume increase and spatial shifts of chromosome territories in nuclei of radiation-induced polyploidizing tumour cells. Mutat. Res.: Genet. Toxicol. Environ. Mutagen. 756: 56-65