Prof. Dr. Dr. Christoph Cremer
Prof. Dr. Dr. Christoph Cremer
(1983 - 2011 Director Research Area "Applied Optics & Information Processing)
*Since January 2012, the research of Prof. Cremer is continued at the Institute for Pharmacy and Molecular Biotechnology (IPMB), University Heidelberg (Cooperation Unit "Biophysics of Genome Structure") and at the Institute of Molecular Biology (IMB) (Group "Super-Resolution Microscopy"). www.optics.imb-mainz.de
Diploma in Physics (Univ. München);
Since August 1, 2011 Head Lightoptical Nanoscopy/Super-Resolution Microscopy, Institute of Molecular Biophysics, D-55128 Mainz, Germany
Since 2013 Honorary Professor (Physics), University Mainz (JGU)
Functional nuclear organization has emerged as an important topic of epigenetics. For this, methods of far field lightoptical resolution are required beyond the possibilities of conventional epifluorescence microscopy (optical resolution about 200 nm laterally, 600 nm axially). Towards this goal, we have established a variety of superresolution microscopy (“nanoscopy”) methods. Our present spectrum for ‘nanoimaging’ of nuclear structures comprises confocal laser scanning 4Pi-microscopy, Spatially Modulated Illumination (SMI) and Patterned Excitation Microscopy (PEM) devices, and Spectrally Assigned Localization Microscopy (SALM). While 4Pi microcoscopy was applied to superresolution of nuclear pore complex distribution, replication complexes and other nuclear nanostructures (axial optical resolution in the 120 nm range), SMI microscopy made it possible to measure the size of telomeric complexes with a resolution down to few tens of nanometer, and to perform precise size measurements of the compaction status of small, specifically labelled chromatin domains. Using a recently developed SALM technique, Spectral Precision Distance/Position Determination Microscopy (SPDM) with Physically Modifiable Fluorophores (SPDMPhymod), nuclear nanostructures can now be studied on a large scale in 3D intact nuclei down to a lateral optical resolution of individual molecules in the macromolecular range in optical sections of down to few tens of nm thickness. These techniques can be performed with standard fluorescence proteins/fluorochromes. For example, the distribution of individually resolved nuclear pore complex proteins, histones, DNA, FISH labelled repetitive short DNA sequences was determined with a lateral optical resolution down to about 15 nm; the spatial location of two species of single molecules in human cell nuclei (e.g. histones and chromatin remodelling factors; histones and polymerase II) was determined simultaneously by dual color localization microscopy up to a density of ca. 10,000 molecules/µm2. Nanoscopy experiments of other cellular features combining SPDMPhymod and Structured Illumination Microscopy (SIM) indicate that in this way, appropriately labeled chromatin structures may be analysed in 3D intact cells at an optical 3D resolution of 40 – 50 nm.
Future Projects and Goals
Other goals are the application of superresolution microscopy methods to analyse membrane complexes, cell to cell interactions, as well as allergenic responses on the nanostructural level.
A.Szczurek, L. Klewes, J. Xing, A. Gourram, U. Birk, H. Knecht, J. W. Dobrucki, S. Mai, C. Cremer (2017) Imaging chromatin nanostructure with binding-activated localisation microscopy based on DNA structure fluctuations. Nucleic Acids Research 2017, 1–11.doi: 10.1093/nar/gkw1301.
Y. Markaki, M. Gunkel, L. Schermelleh, S. Beichmanis, J. Neumann,M. Heidemann, H. Leonhardt, D. Eick, C. Cremer, T. Cremer, Functional nuclear organization of transcription and DNA replication: a topographical marriage between chromatin domains and the interchromatin compartment (2011) Cold Spring Harbor Symposia on Quantitative Biology 75: 1–18. doi:10.1101/sqb.2010.75.042.
D. Baddeley et al. (2009) Light-induced dark states of organic fluorochromes enable 30 nm resolution imaging in standard media. Biophysical J. 96: L22-L24.
M. Gunkel et al. (2009) Dual color localization microscopy of cellular nanostructures.Biotechnology J. 4: 927 – 938.
M. Gunkel, F. Erdel, K. Rippe, P. Lemmer, K. Kaufmann, C. Hoermann, R. Amberger, C. Cremer (2009), Dual color localization microscopy of cellular nanostructures, Biotechnology Journal: S.927-938
R. Kaufmann et al. (2009) SPDM – Single Molecule Superresolution of Cellular Nanostructures. (2009). Proc. SPIE, Vol. 7185: 71850J1 – 71850J-19.
P. Lemmer, M. Gunkel, D. Baddeley, R. Kaufmann, A. Urich, Y. Weiland, J. Reymann, P. Müller, M. Hausmann, C. Cremer (2008), SPDM: light microscopy with single-molecule resolution at the nanoscale, Applied Physics B, Lasers and Optics, DOI 10.1007/s00340-008-3152-x
J. Reymann, D.Baddeley, M. Gunkel, P. Lemmer, W. Stadter, T. Jegou, K. Rippe, C. Cremer and U. Birk (2008), High-precision structural analysis of subnuclear complexes in fixed and live cells via spatially modulated illumination (SMI) microscopy, Chromosome Research 16: 367-382
D. Baddeley, C. Batram, Y. Weiland, C. Cremer, U. Birk (2007) Nanostructure analysis using spatially modulated illumination microscopy. Nature Protocols 2, 2640-2646
G. Kreth, S.K. Pazhanisamy, M. Hausmann, C. Cremer (2007), Cell type-specific quantitative predictions of radiation-induced chromosome aberrations: A computer model approach. Radiat. Res. 167: 515–525
T. Cremer & C. Cremer (2001) Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nature Reviews Genetics 2: 292 – 301
Derzeit geförderte Forschungsvorhaben von C. Cremer an der Universität Heidelberg (2009-2011)
- Associate Principal Investigator im Cluster Cell Networks (2007-2011).
- Principal Investigator in der IWR Graduate School (2007-2011).
- Principal Investigator in der "Global Networks Collaboration" Universität Heidelberg – The Jackson Laboratory/ME (2008-2010).
- Kooperationspartner im Frontierprojekt (Dr. M. Wassenecker) des Instituts für Pflanzenwissenschaften (2008-2010).
- Mitprojektleiter im Frontierprojekt (Prof. G. Fricker) des Instituts für Pharmazie und Molekulare Biotechnologie (2009-2011).
2. DFG, BMBF:
- Mitprojektleiter im DFG Projekt Ionenkanalanalyse (Prof. Katus, Prof. Karle, Dr. Zitron) der Medizinischen Universitätsklinik (2008-2011).
- Kooperationspartner im BMBF Spitzencluster Biotechnologie – Technologieplattformen Stammzellenforschung, Genregulation (2008-2013).
by arrangement, INF 229, room 044 (Tel. 06221-54-8463)