Prof. Dr. Thorsten Hugel
University of Freiburg
T +49 761 203 6192
Single molecule methods are essential for gaining a thorough understanding of complex biological processes. This approach allows real time observation of signalling processes and of molecular machines at work. We use a variety of methods based on single molecule fluorescence and Förster Resonance Energy Transfer (FRET) to address dynamics on a wide timescale from less than a microsecond to several minutes. This is necessary for example for understanding how binding of small molecules (performed in less than a millisecond) can result in large conformational changes (taking up to seconds) and finally to regulation of protein expression levels in a cell.
The multidisciplinary nature of our research requires close collaboration with many colleagues in the fields of biology, biochemistry, medicine, biotechnology and physics.
Fluorescence, FRET, Single Molecule, Signalling, Molecular Machines, Hsp90, Conformational Dynamics
How can a protein system be more than the sum of its components? I am convinced that such systems have to be dynamic and out of thermodynamic equilibrium. Single molecule FRET is ideal to study such systems.
10 selected publications:
- Nanosecond structural dynamics of the chaperone Hsp90
Sohmen B, Beck C, Seydel T, Hoffmann I, Hermann B, Nüesch M, Grimaldo M, Schreiber F, Wolf S, Roosen-RungeF, Hugel T (2021)
- 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 (2021).
Chem Sci. 12(9):3350-3359.
- Controlling protein function by fine-tuning conformational flexibility.
Schmid S, Hugel T (2020).
- Conformational dynamics of a single protein monitored for 24 h at video rate.
Ye W, Götz M, Celiksoy S, Tüting L, Ratzke C, Prasad J, Ricken J, Wegner S V, Ahijado-Guzmán R, Hugel T* and Sönnichsen C* (2018).
- Precision and accuracy of single-molecule FRET measurements—a multi-laboratory benchmark study.
Hellenkamp B, Schmid S, et int., Hugel T (2018).
Nat Methods. 15, 669.
- Multidomain structure and correlated dynamics determined by self-consistent FRET networks.
Hellenkamp B, Wortmann P, Kandzia F, Zacharias M, Hugel T (2017).
Nat Methods. 14(2):174-180.
- Folding and assembly of the large molecular machine Hsp90 studied in single-molecule experiments.
Jahn M, Buchner J, Hugel T, Rief M (2016).
Proc Natl Acad Sci U S A. 113(5):1232-7.
- Four-colour FRET reveals directionality in the Hsp90 multicomponent machinery.
Ratzke C, Hellenkamp B, Hugel T (2014).
Nat Commun. 5:4192.
- Heat shock protein 90's mechanochemical cycle is dominated by thermal fluctuations.
Ratzke C, Berkemeier F, Hugel T (2012).
Proc Natl Acad Sci U S A. 109(1):161-6
- The large conformational changes of Hsp90 are only weakly coupled to ATP hydrolysis.
Mickler M, Hessling M, Ratzke C, Buchner J, Hugel T (2009).
Nat Struct Mol Biol.16(3):281-6.