Universität Bonn

Biophysical Chemistry - Prof. Dr. U. Kubitscheck

Biophysical Chemistry
Prof. Dr. U. Kubitscheck
Ulrich Kubitscheck jpg
© U. Kubitscheck

Biophysical Chemistry

Bild1
© Uni Bonn

The Biophysical Chemistry working group focused on the analysis of molecular dynamics in biological and biomimetic systems. 
Our core area was the analysis of molecular kinetics within supramolecular complexes at the single-molecule level. To this end, we used and methodically developed state-of-the-art light microscopy techniques such as Airyscan microscopy, single-molecule microscopy with various illumination techniques, and light-sheet fluorescence expansion microscopy.

The working group was closed at the end of September 2025. Prof. Dr. Ulrich Kubitscheck (u.kubitscheck@uni-bonn.de) now works as a systemic consultant and coach (www.coaching-kubitscheck.de1) and looks forward to your enquiry. In addition, he remains available for project consulting, scientific expert opinions and lectures, as far as possible.

For support in carrying out further projects using advanced light microscopy, please contact Dr. Jan Peter Siebrasse (jpsiebrasse@uni-bonn.de) or Prof. Dr. Ulrike Endesfelder (endesfelder@uni-bonn.de).

Research 

Analysis of the Transport and Nuclear Export of RNA Particles in vivo

RNA transport 2
© Uni Bonn
Single Export Event
© Uni Bonn

Simplified Principle of the mRNA Export

Complexes of mRNA molecules, proteins and export factors during the export through a nuclear pore complex in the nuclear envelope. The DEAD-box RNA helicase Dbp5 is located at the cytoplasmic face of the pore. The removal of the export factors by Dbp5 accomplishes the directionality of the mRNA export.


Light Sheet Fluorescence Microscopy (LSFM)

Building a microscope 2
© Uni Bonn
Beam path of the first generation of our custom-developed light sheet fluorescence microscope (from 2012).

Development of a Dedicated Light Sheet Microscope for Expanded Samples

Features

Simultaneous and fast image acquisition in two colors

For large and transparent samples up to a volume of 20x20x2 mm³

Automated, stable image acquisition for hours

Building a microscope 3
© Uni Bonn
LSM 3
© Uni Bonn

Design of New Light Sheet Profiles

Improvement of the Optical Resolution and Imaging Frame Rate

(1) Limited resolution and field size when using a light sheet with a Gaussian intensity profile

(2) Reduction of the light sheet thickness by using Bessel beam illumination

(3) Fast frame rates using thin light sheets by horizontally dithering a „lattice“ of Bessel beams


Expansion Microscopy

Idea:
Physical expansion of samples allows to resolve finest details.
An effective super resolution microscopy becomes possible using conventional techniques.

Advantages:
Transparent specimen
Refractive index identical with that of water

Disadvantages:
Fixed samples only

ExM 2
© Uni Bonn
ExM 3
© Uni Bonn

Light Sheet Expansion Microscopy of Mouse Brain Sections

(A) Mouse dentate gyrus granule cells expressing EGFP. Maximum intensity projection of an expanded mouse brain slice, imaged with a custom LSFM.
Size 1150 x 1010 x 483 µm³ (40 z-stacks, step size of 300 nm, 15% overlap), (B) Magnification of the ROI marked in A, lateral field size 236 x 244 µm2, (C) 3D view of B comprising 864 slices of the stack. In red the segmentation and tracing of one neurite, (D) dendrite with its dendritic spines segmented and reconstructed in 3D (see ROI marked in B).


Analysis of the mode of action of antibiotics on bacteria

Goals and Approaches

Visualize components of the cell wall biosynthesis machinery (CWBM) in Staphylococcus aureus
•Generation of strains expressing labeled CWBM components
•Super resolution microscopy
•Visualization of protein and membrane microdomains

Study the impact of antibiotics on localization
•Antibiotics with varying degrees of membrane impairment
•Time-resolved super resolution microscopy
•Monitor cell viability

Quantify dynamics between CWBM components and antibiotics in vitro
•Membrane bilayer systems
•Study the impact of membrane properties

Bacterien Antibiotika
© Uni Bonn
S. aureus 1
© Uni Bonn

Concept ad Central Question:

How do antibiotics affect the organization of the cell wall biosynthesis machinery (CWBM)?

Wird geladen