Mechanistic understanding of signalling by single-molecule fluorescence

Prof. Dr. Thorsten Hugel (CIBSS-AI), Institute of Physical Chemistry (Faculty of Chemistry and Pharmacy), University of Freiburg

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Signalling complexes are not static, but they are dynamic in two ways. First, they continuously assemble and disassemble. Second, their different components undergo coupled conformational changes themselves. In this project, methods based on single-molecule FRET shall be used and further developed to obtain a dynamic (time resolved) view on signalling at high spatial and temporal resolution.

Our group has pioneered several methods to investigate the dynamics of protein complexes and their structure in in vitro systems. The aim of this project is to develop some of these methods to be applied in live cells. You will start with standard two color single molecule FRET on the example of Hsp90 and stress signalling inside and outside phase separated domains in live cells. Together with the Sawarkar lab (MPI-IE, Area A) we will span the spatial scale from single molecules to complete cells in a time-resolved way.


Publications resulting from the project:

Hierarchical dynamics in allostery following ATP hydrolysis monitored by single molecule FRET measurements and MD simulations.
Wolf S, Sohmen B, Hellenkamp B, Thurn J, Stock G, Hugel T.
Chem Sci. 2021; doi: 10.1039/d0sc06134d.

The onset of molecule-spanning dynamics in a multi-domain protein.
B. Sohmen, C. Beck, T. Seydel, I. Hoffmann, B. Hermann, M. Nüesch, M. Grimaldo, F. Schreiber, S. Wolf, F. Roosen-Runge & T. Hugel
arXiv (2021). (in revision)