Prof. Dr. Dr. Christoph Cremer

Prof. Dr. Dr.Christoph Cremer
Kirchhoff Institut für Physik
Im Neuenheimer Feld 227
D-69120 Heidelberg
Phone: ++49-(0)6221-549252 (549271)
Fax: ++49- (0)6221-549112
Email: cremer@bmm.uni-heidelberg.de
cremer@kip.uni-heidelberg.de

Zur Person

Diplom in Physik (Univ. München)
Dr.rer.nat. in Biophysik/Genetik (Univ. Freiburg)
Dr.med.habil. für Allgemeine Humangenetik und Experimentelle Zytogenetik (Univ. Freiburg)
Professor (Ordinarius) für Angewandte Optik & Informationsverarbeitung, KIP / Kirchhoff Institut für Physik & Direktor Biophysik der Genomstruktur, Institut für Pharmazie und Molekulare Biotechnologie (IPMB), Universität Heidelberg; Leiter 4Pi/SMI LaborLabor, Bioquant-Zentrum, Universität Heidelberg.
Mitglied der Fakultät für Physik und Astronomie, sowie (kooptiert) der Fakultät für Biowissenschaften und der Medizinischen Fakultät Mannheim der Universität Heidelberg.
Zweiter Sprecher des Senats der Universität Heidelberg (2006-2009).
Adjunct Senior Staff Scientist, The Jackson Laboratory, Bar Harbor/ME (seit 2002); Professor (adjunct) University of Maine / Institute for Molecular Biophysics (IMB)

Seit 1.8.2011 Leiter Lichtoptische Nanoskopie am Institute of Molecular Biology, D-55128 Mainz
emails: cremer@kip.uni-heidelberg.de, cremer@bioquant.uni-heidelberg.de, cremer@bmm.uni-heidelberg.de, ccremer@jax.org, c.cremer@imb-mainz.de

Gegenwärtige Forschung (nur englisch)

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 ca. 600 nm thickness. This tech nique can be performed with standard fluorescence proteins/fluorochromes and is applicable also in vivo. For example, the distribution of individually resolved nuclear pore complex proteins, histones, or 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. 1000 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.

These superresolution microscopy can also be applied to other biological nanostructures. Our present experience using SPDM comprises single molecule resolution in membranes, cell junctions, bacteria, and viruses. Under optimum conditions, we presently achieve an optical resolution potential of 5 nm (ca. 1/100 of the exciting wavelength).

Perspectives: The focus of our future research will be to further improve these methods and apply them in collaborative projects in epigenetics and biophysics.

Zukünftige Projekte und Ziele

Further goals are the application of superresolution microscopy methods to analyse membrane complexes (present collaboration partners in Cardiology, cancer research, and molecular cell biology of plants.

Ausgewählte Publikationen

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, D. Crossman, S. Rossberger, J. E. Cheyne, J. M. Montgomery, I. D. Jayasinghe, C. Cremer, M. B. Cannell, C. Soeller (2011) 4D Super-Resolution Microscopy with Conventional Fluorophores and Single Wavelength Excitation in Optically Thick Cells and Tissues, PLoS ONE 6(5): e20645. doi:10.1371/journal.pone.0020645

R. Kaufmann, P. Müller, G.L. Hildenbrand, M. Hausmann, C. Cremer (2011) Analysis of Her2/neu membrane protein clusters in breast cancer cells using localisation microscop, J. of Microscopy 242: 46–54.

Y.Weiland, P. Lemmer, C. Cremer (2011) Combining FISH with Localisation Microscopy, Superresolution Imaging of Nuclear Genome Nanostructures, Chromosome Research 19: 5 – 23.

D. Hübschmann, N. Kepper, C. Cremer, G. Kreth (2010) Quantitative Approaches to Nuclear Architecture Analysis and Modelling, in: N.M. Adams and P.S. Freemont (eds.), Advances in Nuclear Architecture, 87 – 129. DOI 10.1007/978-90-481-9899-3_3, Springer Inc.

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.

M. Bohn et al. (2010) Localization microscopy reveals expression dependent parameters of chromatin nanostructure. Biophys. J. 99: 1358 – 1367.

J. Rouquette et al. (2010) Functional nuclear architecture studied by microscopy (2010). International Review of Cell and Molecular Biology 282: 1 – 90.

C. Cremer et al. (2010) Far field fluorescence microscopy of cellular structures @ molecular resolution, In: Nanoscopy and Multidimensional Optical Fluorescence Microscopy (A. Diaspro, Edit.), pp. 3/1 – 3/35. Taylor & Francis.

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

Publikationen...

Derzeit geförderte Forschungsvorhaben von C. Cremer an der Universität Heidelberg (2009-2011)

1. Exzellenz-Initiative:

- 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).

Sprechstunde
Freitag 10:30 bis 11:415, INF 227, Seminarbox 02.107 / Raum 2.111

Applied Optics