Development of innovative microscopy methods

Excellence Cluster “Microscopy at the Nanometer Range” strengthens research of Göttingen’s neuroscientists

The brain is probably the most complex structure ever created by nature: all functions such as sensing, thinking, learning, remembering or forgetting are controlled through molecular signal pathways in neuronal cells. For several years now an interdisciplinary group of scientists in Göttingen has been working on decoding the fundamental processes. For this purpose the Excellence Cluster 171 “Microscopy at the Nanometer Range”, established at the Georg-August-University in 2006 as part of the Excellence Initiative, has developed the suitable “research instruments”. As technology platform for innovative microscopy methods the cluster extends and strengthens the activities at the DFG Research Centre Molecular Physiology of the Brain (CMPB).



The scientists at the CMPB which was established in 2002 investigate the molecular processes and interactions in neuronal cells in five key areas, with the aim of decoding the plastic functionality of the complex networks of highly specialised neural cells in the human brain. Central topics in addition to the fundamental research are neurological and psychiatric diseases based on brain development disorders or neurodegeneration. Thanks to innovative procedures in the field of high-resolution microscopy it is now possible to capture what exactly occurs in the neural cells.

A particularly powerful optical microscope allows biologists to observe molecular structures in the nanometer range in living cells. The Excellence cluster has established this so-called STED-microscopy in a junior research group under the leadership of Dr. Silvio Rizzoli and will adjust it to suit the requirements of intravital experiments. On the basis of new recording techniques it has since been possible to register and record fast movement processes on molecular level with a resolution of 65 to 70 nanometers.

A further junior research group was started in the area of Atomic Force Microscopy (AFM) to observe dynamic biological processes at nano level. The aim of the activities led by Dr. Iwan Schaap is to further develop the efficiency of data recording and processing of this microscopy method. A particular objective is the observation of the vital transport processes in the neural cells through use of the AFM. At the centre of the research is the question how molecular congestion within the cell can be prevented and in what way the molecular exchange process is coordinated.

Construction and structure of the molecules are decisive for maintaining normal, interaction-based cell and brain functions. To investigate such molecular structures further, the junior research group led by Dr. Lars T. Kuhn applies nuclear magnetic resonance (NMR) spectroscopy. An important research aspect in this case is the improvement of the signalling sensitivity. This way the scientists hope to gain new insights into the origins of neurodegenerative disease patterns such as Alzheimer’s, Parkinson’s or Creutzfeld-Jakob-disease. In the long term, new therapeutic approaches are to be developed based on these findings.

In further research areas within the Excellence cluster several research groups are working on the development and optimisation of so-called multimodal techniques in fluorescence microscopy. As well as microscopic research methods with coated nanoparticles these include different variants of the Fluorescence Resonance Energy Transfer (FRET) and the Fluorescence Lifetime Imaging (FLIM). These will be applied to visualise defined molecule interactions and molecular transport. With the two photon microscopy such molecular processes can also be displayed in intact systems, which makes it possible to undertake molecular-physiological analyses under intravital conditions.

The project “X-Ray Microscopy” is dedicated to the further development, adjustment and application of x-ray microscopy for high-resolution investigation of structures of neuronal cells and organelles. Here the potential of x-ray is to be extended through the use of an innovative, lensless reproduction technique on the basis of a holographic reconstruction.

Where will the Göttingen Excellence cluster “Microscopy at the Nanometer Range” be in three years? To assemble the best innovative microscopy technologies the established Excellence areas will define cooperative tasks: here the analysis of the structure and function of normal and pathological proteins or protein complexes is of particular interest. In this context research will also be undertaken to investigate their effects on the interaction with cells and their environment. The aim of the networked and interactive research efforts is the development of innovative “probes” with exchangeable molecular markers that can also be used for diagnostic purposes, potentially even on humans.