Christoph Cremer

Christoph Cremer ( born July 12, 1944 in Freiburg im Breisgau ) is a German physicist and professor at the Ruprecht -Karls- University of Heidelberg and the Institute for Molecular Biology in Mainz, the conventional light optical resolution limit ( " Abbe limit " ) by different methods has overcome (1996 localization microscopy SPDM in 1997 spatially structured illumination SMI).

Life

Christoph Cremer comes from a family with a scientific and socio - theological background, as was Father Hubert Cremer Professor of Mathematics and large computer systems at RWTH Aachen University, his uncle Lothar Cremer is regarded as one of the leading scientists of the 20th century in the field of acoustical engineering and its Aunt Erika Cremer, developer of the foundations of Adsorptionsgaschromatographie, 1940 was the first physics professor at the University of Innsbruck. Cremers mother Elizabeth Rahner described already in the 1930s years still current forms of cooperation between parents and child-care facilities, whereas their brothers Karl Rahner and Hugo Rahner are considered extremely important theologians of the past century.

His brother Thomas Cremer is also active as a professor of medicine at the Ludwig- Maximilians- University of Munich in science, while the youngest brother Georg Cremer, Professor of Economics, General Secretary of the German Caritas Association is.

After a few semesters of philosophy and history at the universities of Freiburg and Munich, Christoph Cremer studied physics (supported by the Study Foundation of the German people ) in Munich and a PhD in Genetics / Biophysics in Freiburg. This was followed by a post-doctoral research at the Institute for Human Genetics at the University of Freiburg, a multi-year stay in the USA at the University of California and the Habilitation ( Dr. hab. Of General Human Genetics and Experimental Cytogenetics, Medical Faculty, University of Freiburg). Since 1983 he has been Professor (2004 full professor ) for Applied Optics and Information Processing at the University of Heidelberg, at the Kirchhoff Institute for Physics. In addition, he is a scientific member of the Interdisciplinary Center for Scientific Computing (IWR ), the Institute of Pharmacy and Molecular Biotechnology, and the Bioquant center of the university.

Christoph Cremer is involved in three ongoing projects of excellence (2007-2012) of the University of Heidelberg and partners in the biotechnology cluster for cell- based and molecular medicine, one of the five granted in 2008 the German BMBF tips cluster. As an elected second Speaker of the Senate (since 2006) to Cremer also involved higher education policy at the University of Heidelberg. In his role as, Adjunct' professor at the U.S. University of Maine and a scientific member of the renowned Jackson Laboratory (Bar Harbor / Maine, USA), where he is researching several weeks a year during the holidays, it is at the local structure of a biophysical Centre ( Institute for Molecular Biophysics, IMB) involved, the Global Network ' project is connected with the University of Heidelberg in one. He is married to the architect and artist Letizia Mancino - Cremer, since 1992 chairman of the Goethe Society of Heidelberg.

  • Super Resolution Microscopy by Prof. Christoph Cremer

Localization microscopy of individual flashing YFP molecules / SPDMphymod

Two-color localization microscopy SPDMphymod / Super Resolution Microscopy with GFP and RFP fusion proteins

Marker / probe -free localization microscopy SPDM - previously unseen cell structures are detectable

Studies on menschl. Retinal tissue, contracted by macular degeneration AMD, 100nm resolution with structured illumination

Virus Super Resolution Microscopy SPDM Cremer / paths labs

Main developments

Concept of 4Pi microscopy

Cremer was involved early in the development of laser-based light microscopy. The first ideas for this already came from his doctoral research in the 1970s. Together with his brother Thomas Cremer, now Professor of Anthropology and Human Genetics at the Ludwig -Maximilians University of Munich, Christoph Cremer suggested in a patent in 1971 the development of a hologram based 4Pi laser scanning microscopy (DE Laid-Open Patent 2,116,521 ) ago. This patent document already contains initial ideas for use of photoswitchable molecules to improved light-optical production of nano- structure information.

The basic idea was to laser light from all sides ( solid angle 4Pi ) to focus on a " spot" with a diameter smaller than that of the conventional laser scanning microscopy and scanning with this object point by point; so should the optical resolution beyond the conventional limit ( about 200 nm lateral, 600 nm axial) are also improved. Since 1992, the 4Pi microscopy (currently Director at the Max Planck Institute for Biophysical Chemistry, Göttingen ) developed using two opposed microscope lenses with a high numerical aperture of Stefan Hell to a powerful high-resolution imaging.

First DNA - irradiation technique for living cells

In the early 1970s the brothers Christopher and Thomas Cremer developed a laser - UV - micro- irradiation apparatus, which for the first time enabled the targeted irradiation of a partial region of living cells in the absorption maximum of DNA ( 257 nm ) and 60 years of age usual conventional UV Partialbestrahlung replaced. It could for the first time as specific (ie at preselected sites in the nucleus of living cells) caused DNA lesions, without turning the division or cell viability. Specific small cell districts could mikrobestrahlt and dynamics of macromolecules present there are estimated quantitatively. Moreover, the high speed of the process fraction of a second exposure time allowed for the targeted irradiation of a moving cell organelles. This development provided the basis for important experiments in the field of research into the genetic material is (proof of " chromosome territories" in living mammalian cells) and resulted in 1979/1980 to a successful collaboration with the biologist Christiane Nüsslein -Volhard (now Director of the Max Planck Institute for Developmental Biology, Tübingen, Nobel Prize 1995). Christoph Cremer continued cooperation in this one its laser - UV - micro- irradiation apparatus to produce cellular changes in early larval stages of Drosophila.

Development of confocal laser scanning microscopy for fluorescence

On the basis of experience in the construction and application of laser - UV - micro- irradiation apparatus experiences Cremer Brothers conceived in 1978, a light- optical laser-scanning method in which the three-dimensional object surface were scanned by a focusing laser beam pointwise and there stimulated specifically marked areas for fluorescence. The image was then similar to the scanning electron microscope or the scanning Optical Microscope by Davidovits and Egger (U.S. Patent 3,643,015, 1972) composed by electronic means pointwise.

Particular attention was paid, however, given to a) the imaging of specific fluorescently -labeled structures, b) the increase of the signal contrast in the axial direction by means of a mounted in the image plane of the small aperture to the diameter of the diffraction disk where generated by a dot-shaped fluorescent object; this basic idea of confocal microscopy was filed in 1957 by Marvin Minsky 's patent, but without reference to laser light sources (these were not yet available) and excluding fluorescence excitation. Another difference to related concepts microscopy consists in the fact that was omitted due to the data collected by Cremer & Cremer experimental experiences with highly stable gas lasers at their microscopy method to the " excitation pinhole ".

This construction plan of a confocal laser scanning fluorescence microscope ( CSLM ), with the laser scanning method with the three-dimensional ( 3D) detection of fluorescent objects was connected for the first time, Christoph Cremer brought his professorship at the University of Heidelberg. The in the following decade in particular working groups at the University of Amsterdam and at the Heidelberg European Molecular Biology Laboratory ( EMBL) and the associated industrial partners technically developed for practical application Confocal laser scanning fluorescence microscopy held in the later years a wide catchment in the molecular biology and biomedical laboratories and provides still the gold standard is, as far as it comes to three-dimensional light microscopy with conventional resolution.

Super Resolution Microscopy

In many cases, the objective of the microscope is the fact to determine sizes of individual small objects. In conventional fluorescence microscopy is also possible only up to values ​​that lie at the conventional optical resolution limit of about 200 nm ( lateral). The group of Christoph Cremer has various super-resolution microscopes, such as the Vertico SMI developed, based on different technologies and requirements. Currently, a resolution of 5 nm in 2D and a determinable molecular density of about 2.8 × 104 microns -2 is achieved.

Structured illumination SMI

Mid-1990s, Christoph Cremer began with the development of a light- microscopic method, which allowed for a significant improvement in the resolution size of fluorescently labeled cellular nanostructures. This time he used the principle of wide-field microscopy in conjunction with a structured laser illumination ( SMI: spatially structured illumination, English spatially modulated illumination. ). This will present a resolution 30-40 nm ( about 1 /16 - 1/13 of the wavelength used ) achieved. Additionally, this technology was no longer subject to the speed limits of the focusing microscopy so that so that the 3D analysis of whole cells in short observation times ( a few seconds currently in the field ) is possible.

Localization microscopy SPDM

Designed Also since the mid-1990s and realized Christoph Cremer fluorescence optical method of wide-field microscopy, which (in the sense of the smallest detectable distance between two localized objects) to a multiple of the conventional resolution have been aimed at improving the effective optical resolution ( SPDM, localization microscopy, English. spectral precision distance / position determination microscopy).

SPMDphymod - localization microscopy with standard fluorescent molecules

2008 Cremers found working group that, under certain conditions photophysical many " ordinary " dye molecules such as GFP, RFP, YFP, fluorescein or Alexa dyes, and not only photo-switchable dyes for optical nano copy can be used. The combination of many thousands of individual shots of the same cell were using laser- precision optical measurements " localization images " obtained with significantly improved optical resolution. This expands the applicability of the method on many areas SPDM biophysical, cell biological and medical research.

LIMON: 3D Super Resolution Microscopy

LIMON (Light Microscopical nanosizing microscopy) was developed in 2001 at the University of Heidelberg and combines the two methods Localization Microscopy and Structured Illumination for 3D Super Resolution Microscopy with a resolution of 40 nm in 3D. For through this two-color Kolokalsiations 3D microscopy, the spatial arrangement of the two active genes Her2/neu in breast cancer and HER3 determined with an accuracy of about 25 nm, and for carcinogenesis probably relevant clustering was analyzed at the single molecule level.

Award

  • Heidelberg Innovation Forum 2009: Fastest light microscope in the world named the best business idea.
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