Randall Division o f Cell and Molecular Biophysics

You are in: School of Biomedical Sciences Schools Home

Dr. Rainer Heintzmann Head of the “Biological Nanoimaging” research group, Randall Division, King’s College London 2004- Head of the "Multidimensional Microscopy" research group, Dept. of Molecular Biology, MPI for Biophysical Chemistry 2002 - 2004 Postdoctoral Fellow at the Max-Planck-Institute for Biophysical Chemistry, Department of Molecular Biology (Director: Dr. T. Jovin), Göttingen, Germany 2000 - 2001 PhD in Physics, University of Heidelberg; 1999 "Diplom" (Physics Diploma) at the University of Osnabrück One-year thesis on "X-Ray Diffraction by Holographic Structures in Oxidic Materials" 1996 E-mail:rainer.heintzmann@kcl.ac.uk

New Webpage. Click here

Research Interests

Imaging Cell Function at High Resolution -

The Biological Nanoimaging group focuses on developing techniques to measure multidimensional information in small biological objects such as cells, cellular organelles, molecules or other structures of interest.
Molecules interact in living cells at specific places (e.g. inside organelles) and often at well defined times (e.g. after stimulation with other molecules). Much biological research is now focused onto unraveling these details. Luckily there are a number of physical effects, which can be used tell things apart, when one or multiple molecules are fluorescing (either by themselves or by having a specific fuorophore attached to them).

• Interacting molecules are very close to each other and can exchange energy (via the Förster resonance energy transfer, FRET). This effect can be detected in the microscope and visualized. One of the research projects devises new strategies to follow the time course of molecular interaction in the cell without having to destroy the acceptor fluorophore.

• Fluorescent molecules have a characteristic decay time after excitation (the fluorescent lifetime, which is typically a few nanoseconds). This decay time depends on the molecule, but also on the local environment and the proximity of other molecules. If a large number of excitation photons hit the fluorescent molecule (fluorophore), it is not capable of sending out a proportional number of emission light, since every event of emission takes some time. This effect is called excited state saturation and the aim of a research project is to use this for quantitative microscopy (optical resolution improvement, FRET quantification, estimation of molecular concentrations in the cell, discriminating between molecular species).
• Recently a number of molecules have been found that can be switched between different fluorescent states by illumination at seperate wavelengths. The transitions between these states can be driven into saturation. The arising non-linear dependencies offer the unique possibility of a theoretically unlimited optical resolution. Part of our work focusses on an experimental demonstration of high resolution based on these effects.
• At very high light intensity a process that is called multi-photon absorption is possible. Using this effect it is possible to illuminate a rather thick biological sample such as tissue or even small organisms with infrared light and excite (e.g. via two-photon absorption) specific fluorescent molecules, which then emit light in the visible region of the spectrum. The increased penetration depth of the infrared light and the decreased scattering allow to obtain 3D images of larger specimens than otherwise possible. A suitable system will be present in the group in the very near future and it will be used in combination with other ideas to further increase the possibilities of deep tissue imaging.
• Multi-spectral information can be obtained with a number of approaches. Future research in the group includes the development and application of multi-spectral fluorescence imaging based on Fourier-encoding excitation as well as emission.
  The group of Rainer Heintzmann has just started (since summer 2004) at King's college. Previously he was heading the Multidimensional Microscopy group in the Department of Molecular Biology at the Max Planck Institute for biophysical Chemistry, Göttingen, Germany.

In addition to the application oriented collaborations with the various groups at the Randall Division and outside, collaborations are also intended with research groups of similar orientation focussing on the physical and technological aspects. It is also intended to establish a strong link to Optical Microscopy and the Department of Physics located at the Strand campus of King's college.

If interested in this fascinating field of research have a look at the open positions.

Current members of the Group:
Dr. Rainer Heintzmann (rainer.heintzmann@kcl.ac.uk)
Dr. Martin Beutler (martin.beutler@kcl.ac.uk)
Liisa Hirvonen
Ondrej Mandula
Jakub Nebdal

Teaching
Videos of two recent lectures given in the IP-EAMNET workshop
Dynamic Imaging Microscopy & Analysis for Biologists
in Paris are available online:
•  Prospects and practice for high resolution imaging
and
•  Image Processing Tools

Software written:
• "Rewrite", a flexible system for symbolic mathematics (C, 1991-1996)
• "VoiceRecog", a system for speech-regognition of unknown speakers (objective C, 1994)
• Library for Image Processing, and ML-Deconvolution (C++, 1996 - )
• "View5D", 5D data visualization tool for microscope images (Java applet, ImageJ plugin, 1998 - )

Selected Recent Publications

R. Heintzmann and C. Cremer. Axial tomographic confocal fluorescence microscopy, J. Microsc., 206, 7-23, 2002.

R. Heintzmann, T.M. Jovin, and C. Cremer. Saturated patterned excitation microscopy (SPEM) - a novel concept for optical resolution improvement. J. Opt. Soc. Am. A, 19, 1599-1609, 2002.

D.S. Lidke, P. Nagy, R. Heintzmann, D.J. Arndt-Jovin, J.N. Post, H. Grecco, E.A. Jares-Erijman and T.M. Jovin. Quantum dot ligands provide new insights in receptor-mediated signal transduc¬tion. Nature Biotechnology, 22, 198-203, 2004

R. Heintzmann., K.A. Lidke, T.M. Jovin. Double-pass Fourier transform imaging spectroscopy. Optics Express. 12, 753-763, 2004.

N. Schaffert, M. Hoßbach, R. Heintzmann, T. Achsel and R. Lührmann. U4/U6 di-snRNPs accumulate in Cajal bodies upon RNAi knockdown of hPrp31, indicating a role of Cajal bodies in U4/U6.U5 tri-snRNP assembly. The EMBO J. 23, 3000-3009