In the nervous system, signal transduction between cells occurs in specialized contact zones, the synapses. Ligand-gated ion channels are important components of synapses. They bind presynaptically released neurotransmitters, which, by opening the ion channel, leads to the depolarisation of the postsynaptic cell . The nicotinic acetylcholine receptor (nAChR) is a prototype of this entire category of ion channels. 
In an attempt to elucidate the mechanisms of ion channel opening, we characterize the binding sites of the nAChR for various classes of ligands, including toxins from snake and wasp venoms, that are known to influence the nAChR's structure and function. (This work is performed in a long-lasting co-operation with Prof. Tsetlin's Laboratory of Neuropeptide Receptors at the Shemyakin-Ovchinnikov-Institute for  Bioorganic Chemistry in Moscow.) To this purpose we use protein chemical methods, such as HPLC, chemical micro-sequencing, MALDI and ESI peptide mass spectrometry, as well as biophysical techniques, such as fluorescence or FTIR spectroscopy. 
Another main focus on this project is the expression and structure determination of distinct nAChR domains that are important for receptor regulation. 
 

Inside the nucleus, the inner nuclear membrane forms a surface that might harbor signalling processes. So far, only a few protein components of this membrane have been characterized. However, they exert an influence on the functional organization of the nucleus. We aim to identify and functionally characterize novel proteins of the inner nuclear membrane and plan to describe their phosphorylation-dependent interactions with nuclear proteins. The lamina-associated polypeptide 2beta (LAP 2beta) is integrated into that membrane and serves as a model protein of this structure in our studies. The search for binding partners and the characterization of protein-protein-interactions is performed using a combination of molecular biology and cell biochemistry techniques (expression of recombinant proteins, cell culture using fibroblasts and neuroblastoma cells). 
 

At the synapses, adaptation processes, during which the signal transduction is modulated, occur upon repeated stimulation.  These processes are essential for learning and for the development of memory.  Supposedly, they are also at the origin of chronic pain. The underlying molecular mechanisms are being investigated in co-operation with the Grünenthal company in a project financed by the German Federal Ministry for Education, Research, and Technology (BMBF). 
Our group's task in this effort will be the identification of proteins which undergo a change in the level of expression or post-translational modification during the development of chronic pain. This will be done using two-dimensional separation techniques and mass spectrometric analysis.
 

Intracellular signal chains are another of our research topics: How does a signal that is received at the plasma membrane travel all the way to the nucleus where, by modulating gene expression, it finally influences the regulation of proliferation and differentiation ? In recent years, a stimulus-dependent translocation into the nucleus was reported for some protein kinases - among them protein kinase C (PKC), the object of our investigations. We aim to identify nuclear binding partners and substrates of PKC and to elucidate the translocation mechanism (PKC does not contain a canonical transport signal). These studies that use molecular biological and protein chemical methods are performed using primary neurons.