Extending and integrating imaging modalities
To visualize even the simplest biological systems requires the ability to simultaneously image different parameters, which necessitates a high level of sensitivity for a microscopy system. Conventional fluorescence microscopy primarily maps the spatial distribution of specific fluorescently labelled molecules. A goal of our work is to develop methods and instruments that make the dynamics of molecules via their associated fluorescence available as robust imaging signals in real time and with high sensitivity. This covers fluctuations of molecular and cellular structures as well as binding, transport and diffusion, that are characterized with spatio-temporal fluorescence fluctuation spectroscopy. Furthermore, as the lifetime of fluorescence can change due to molecular interactions and microenvironmental properties, it can be used as an additional spectral signature for imaging and fluctuation analysis. We combine these approaches into integrated imaging systems. Another goal is to improve resolution in all dimensions (space, time, and wavelength) while further steps may lead beyond fluorescence.
Building new instrumentation for visual biochemistry
While commercial microscopes
provide a variety of such imaging
methods and techniques, there are always applications that require the
modification of an existing system or the development of a new setup.
This requires modeling of the optics, hardware design and construction,
and software development for data acquisiton and processing. In a
recent project, we have built a light-sheet-based microscope for 2D-FCS
imaging, which allowed us to visualise and measure the mobility and
interaction properties of various fluorescent proteins in vivo.
Structure and dynamics of the cell nucleus
The architecture of the cell nucleus is strongly determined by the chromatin structure that is intricately organized, yet at the same time very dynamic. We study this interplay and its impact for example on gene regulation by looking at molecular and structural mobilites and interactions in vivo, also serving as a model application for the new imaging approaches.