Research Interests

Taking advantage of the latest optical microscopy technologies, our group studies the biophysics underlying important biological processes, such as pathogen (virus, bacteria, fungus) infection and the organisation of the plasma membrane.
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​We believe that capturing the molecular dynamics of such processes is key to understanding them. For this we develop and apply many observation tools, including high temporal and spatial resolution imaging techniques and analysis tools such as super-resolution STED microscopy, MINFLUX microscopy.
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Research projects

Optical microscopy: tool development for molecular scale observations in model systems, cells and tissue and microscope facility service
As outlined in the research projects below we are applying and adapting optical microscopy tools for investigations of molecular organization and dynamics in model systems, cells and tissue. For this we apply commercial systems as well as custom-built microscope instruments. Examples, range from optimising recordings of molecular dynamics using Fluorescence correlation Spectroscopy (FCS) in combination with super-resolution STED microscopy (STED-FCS) or Single-Particle Tracking (SPT) employing interferometric SCATtering (iSCAT) or MINFLUX microscopy, over correlative recordings combining lightsheet microscopy (oblique angle single-plane microscopy, OSPIM) to deep tissue adaptations using adaptive optics.

In addition, we are scientifically supporting the establishment, running and adaptation of the new microscope facility of the DFG funded Excellence Cluster “Balance of the Microverse”, housing several turn-key instruments and run by several of our staff members to support microbial research.

Membrane Particle Dynamics
Understanding molecular dynamics is of fundamental importance for the interpretation of most biophysical processes. The detection of particle motion can be achieved through FCS and STED-FCS, in order to achieve high-resolution levels of details. Further signal correlation-based techniques have been developed, such as Image Correlation Spectroscopy and related methods, and are currently being investigated in our group. An alternative, but also complementary, method is the SPT approach, in which the time traces of detected particles are analyzed to lead to particle-specific levels of detail. This approach is currently being applied to iSCAT and MINFLUX microscopy to reach kHz and faster sampling rates.

These methods are applied by our group to gain further insights in the dynamics of membrane-bound molecules, to obtain functional and structural insights on lipid membranes, model and cellular.

Infection: From viruses to microbes and immunology
We are using and further adapting our microscopes to in more detail investigate pathogens (viruses, bacteria, fungi, …), their structures as well as cellular changes during infection. Based on our ongoing research on HIV-1 cell entry and assembly, we are part of several research initiatives (such as the Leibniz ScienceCampus InfectoOptics, the DFG funded Excellence Cluster “Balance of the Microverse”, the Polytarget Collaborative Research Center 1278, Research Training Group (RTG) 2723 Materials-Microbes-Microenvironments, and further planned interdisciplinary projects) to, for example, look at bacterial co-infection during Influenza A virus (IAV) infection in cells, bacterial adhesion on different implant supports, and molecular details during virus and bacterial interactions with cellular membranes as well as virus assembly in host cells. In a Jena-wide joint effort we are further developing photonic based tools for an improved and translational use in the diagnositcs of infection within the Leibniz Center for Photonics in Infection Research (LPI).

Peroxisomal import 
Peroxisomes are less known but still fascinating organelles, essential to the cellular functions. Many steps of various catabolic and anabolic pathways take place in peroxisomes, which makes them crucial for human health. The proteins needed for these different metabolic pathways have to be imported into peroxisomes from the cellular cytosol. This import follows a unique mechanism which is still hardly understood. What is known is that these proteins are synthesized in the cytosol and bind to cytosolic import receptors, which transport and import them into the peroxisomes by becoming an integral part of the peroxisomal membrane, thereby forming a transient translocation pore. This unique import system is very interesting as it allows the import of complete protein complexes.

We use advanced microscopy experiments to characterize the dynamics of the peroxisomal import process by: (1) Super-resolution STED microscopy to highlight compartmentalized protein distributions at the peroxisomal membrane; (2) (STED-)FCS to analyse the interaction dynamics between PEX5 and its cargo proteins; (3) tracking the movement of peroxisomes to understand the molecular mechanisms that trigger their mobility and import, and (4) analyse protein reorganization and pore formation at the peroxisomal membrane through combination of optical microscopy with electrophysiology recordings.

Deep learning
Deep Learning is a set of machine-learning techniques using neural networks that learn effective representations of data with multiple levels of abstraction. Coming from computer vision, these techniques have recently shown an impressive ability to classify, cluster, or segment biophysical data such as fluorescence traces, microscopy images or spectroscopy measurements. Automated data processing pipelines promise to increase reproducibility of experiments by standardizing the analysis of the data.

In a current project, we apply Deep Learning techniques on Fluorescence Correlation Spectroscopy (FCS) data to correct a variety of hardware- and sample-related artifacts, such as photobleaching, contamination from additional slow moving particles, or sudden drops in intensity because of detector anomalies.

Nanoparticles - Polytarget Collaborative Research Center 1278
During the development of new medications, several promising approaches suffer from severe side effects and biodegradation. One approach to address both issues is to use drug-carrying vessels. In a cooperation with Prof. Schubert's and Oliver Wertz’s group, nanoparticles are developed to be used as a drug-delivery system. Due to the typical particle size of 100 - 200 nm, it is not possible for them to diffuse through the cell membrane. Hence, to overcome this barrier, we aim to improve the receptor-mediated uptake of nanoparticles.

Such a system offers the opportunity to use a large library of already developed drugs with a specific targeting and with only minimal side effects.

Gut-on-Chip - Balance of the Microverse Excellence Cluster
Microbial consortia of the human gut are extremely diverse, individualized and essential for host health and fitness. However, gut microbiomes also contain opportunistic pathogens, such as C. albicans, which can cause disease when the microbiome is disturbed. Choice of diet and antibiotic use, removing the protective microbiome, can enrich C. albicans and cause overgrowth, predisposing individuals for systemic infections. In fact, the gut is the main source of life-threatening C. albicans infections. Gut-on-Chip model will be established to investigate the processes and dynamics of interactions of C. albicans with antagonistic bacteria and human intestinal epithelial cells thereby providing the basis to elucidate the principles of balances and dys-balances of gut microbial communities containing opportunistic pathogenic fungi.
In this project we will optimize advanced optical microscopy approaches to in detail quantitatively analyze cell-cell interactions at the sub-micron level, for example of cellular plasma membrane properties before the onset of C. albicans invasion.