Jun. Prof. Dr. Simon Ebbinghaus, Physical Chemistry II, Faculty of Chemistry and Biochemistry

Simon Ebbinghaus

Research Programme:

Protein misfolding and aggregation cause neurodegenerative disorders like Huntington, Parkinson and Alzheimer. With Fast Relaxation Imaging (FReI), we developed a new biomolecular tool to study the early events of aggregation directly in vivo. FReI combines a laser induced microsecond temperature jump with high-speed fluorescence imaging to resolve cellular protein dynamics with high spatio-temporal resolution. Comparative temperature relaxation experiments and biomolecular techniques in vitro will be used to interpret the in vivo results.

Particular spectroscopic methods are fluorescence-, circular dichroism-, infrared- and UV/VIS-spectroscopy. Biochemical and cell biological approaches include PCR-mutagenesis (mutations, chimaera), protein expression, western blot and cell/worm cultures. The experimental data are interpreted using mathematical models to derive quantitative aggregation schemes. Thus, we quantify the challenges that the cellular chaperone network is concerned with to maintain protein homeostasis and to prevent aggregation. Currently, our group utilizes the FReI technique for in-cell kinetic studies to identify pathogenic events that cause protein misfolding and aggregation of the protein Huntingtin (involved in Huntington’s disease). Future perspectives of the new technique include studies of inhibitor interaction with early events of cellular aggregation, introducing FReI for high-throughput in vivo drug screening.