Research Area F: Protein Function/Dysfunction ‘in vivo’
An essential goal of the efforts of CIPSM is an understanding of the functions of proteins in the intact organism. Among the most powerful approaches for such analyses are the use of high-resolution, non-linear optical techniques (e.g. multi-photon imaging) and sensitive biophysical recording methods (e.g. patch clamp) in ‘in vivo’ animal models. These approaches are used for the analysis of the basics mechanisms normal brain function, mostly in the mouse model. Of particular interest is the investigation of the mechanisms mediating synaptic plasticity related to learning and memory formation, to plasticity ion sensory systems, and to the functional integration of newly generated neurons. Another focus is the investigation of mechanisms causing neurodegenerative disorders. Proteins can be completely unfolded and destabilized or can gain a different structure with altered or even novel pathogenic function. The folding problematics will be investigated together with groups in the research areas A and B. Frequently changes of functional properties of these proteins are associated with the deposition of misfolded neurotoxic, amyloidogenic peptides, which cause selective neuronal cell death and affect synaptic plasticity and memory function. In a collaborative network we will investigate the function, regulation and interactions of proteins associated with the most frequent neurodegenerative disorders. Novel compounds aimed to inhibit amyloidogenesis and neurotoxicty will be designed based on the knowledge received from structural analysis, in vivo functional analysis, and protein/protein interactions. Animal models will be generated allowing life imaging of protein deposition and malfunction to evaluate and screen for such components. A direct interaction of clinical and experimental neurology will facilitate the transfer of knowledge from tissue culture systems and animal models to patients.