Research Interests

Taking advantage of the latest optical microscopy technologies, our group studies the biophysics underlying important biological processes, such as viral infection or the organisation of the plasma membrane.

We believe that capturing the molecular dynamics of such processes is key to understanding them. That is why we develop and apply high temporal and spatial resolution imaging techniques and analysis tools.

Research projects

Membrane Particle Dynamics
Understanding the molecular dynamics is of fundamental importance for the interpretation of most Biophysical processes. The detection of particle motion can be achieved through Fluorescence Correlation Spectroscopy (FCS), which can be combined to Stimulated Emission super resolution microscopy (STED-FCS), in order to achieve subdiffraction 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 Single Particle Tracking 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 Interferometric Scattering (ISCAT) 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.

Peroxisomal import - Pertrans Research Group
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) Fluorescence Correlation Spectroscopy (FCS) to analyse the interaction dynamics between PEX5 and its cargo proteins; and (3) tracking the movement of peroxisomes to understand the molecular mechanisms that trigger their mobility.

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.

Imaging HIV entry
To infect a cell, the human immunodeficiency virus fuses its membrane with the cell plasma membrane. For many years, studying this process using fluorescence microscopy was hindered by the small size of HIV virions (around 120 nm and below the resolution limit of classic optical microscopes). Recent developments in super-resolution microsocopy not only allow us to unveil the details of HIV virions during infection, but also to perform advanced measurements of the biophysical phenomena underlying this process. We also aim to develop a minimal model system to study viral entry in a tunable and controlled environment. Our ultimate goal is to understand the mechanism of HIV entry in cells and how neutralising antibodies block this process.

Nanoparticles - Polytarget Collaborative Research
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 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.