 |
 |
|
| |
|
|
| |
Elementary mechanisms of protein folding
By combining rapid correlation spectroscopy with the distance
information available from single molecule FRET, we study
fundamental aspects that govern protein folding dynamics.
This approach has allowed us to map intramolecular distance
distributions and determine nanosecond dynamics that govern
the diffusive search of a protein on its free energy surface.
Closely related topics include the structure and dynamics
of intrinsically disordered proteins and the influence
of crowding on protein folding and dynamics.
|
Effects
of the cellular machinery on protein folding and misfolding
mechanisms
Many aspects of the physical principles governing protein
folding in vitro have been elucidated in the past decades.
At the same time, a large number of cellular components
involved in protein folding in vivo have been
identified. But our mechanistic understanding of how these
cellular components affect the energy landscape of the
folding process has remained very limited, largely due
to a lack of suitable methods. We investigate the role
of cellular factors on protein folding mechanisms with
single molecule fluorescence spectroscopy. Main aspects
of our research are the effects of the ribosome and molecular
chaperones on protein folding. A detailed investigation
of these processes will be crucial for understanding the
fine balance between protein folding and misfolding in
the cell, and the large number of diseases associated
with protein misfolding and aggregation.
|
Single molecule spectroscopy
We use a wide range of biochemical and biophysical methods,
with a focus on the application of single molecule fluorescence
spectroscopy, especially confocal and total internal reflection
fluorescence (TIRF) spectroscopy. Our projects involve
the continuous development and adaptation of new instrumentation
and software, novel types of data analysis, and simulations,
frequently in close collaboration with specialized groups.
Recently, we have started to use the combination of single
molecule detection with microfluidic devices to investigate
heterogeneous nonequilibrium processes with millisecond time
resolution.
|
Protein chemistry
A prerequisite for single molecule FRET experiments is
the site-specific labeling of proteins with suitable fluorophores.
We use modern molecular biology methods, recombinant heterologous
expression, and purification with advanced chromatography
techniques to generate the proteins of choice. We also
develop new methods to improve specificity and versatility
of fluorophore incorporation.
|
Support
|
home
|
|
|
Single Molecule Biophysics
Department
of Biochemistry
 
|
