Current Research Projects

Our lab tries to understand the role of plasma membrane processes particular in the context of early T cell signaling. To this end, we use and develop high resolution single molecule microscopyprotein micro- and nano-patterning, and force microscopy.

Early T cell signalling

Scientific image showing the organization of proteins in the immune synapse between a T-cell and a functionalized supported lipid bilayer

© TU Wien

One of the most striking features of our immune system is its inherent ability to distinguish harmful from harmless based on the primary protein structure of antigens. T-cells embody this trait of adaptive immunity through their unique capability for detecting antigenic peptides. It is driven by αβT-cell receptors (TCRs) on the T-cell binding to particular antigenic peptide-loaded MHC molecules (pMHC) displayed by antigen-presenting cells. T-cells are exquisitely sensitive to antigen: they can detect even a single antigenic pMHC molecule among a great number of structurally similar yet non-stimulatory pMHCs. The molecular/cellular mechanisms underlying this remarkable quality are not at all understood, even though their relevance for both disease progression and intervention can hardly be overestimated.

Single Molecule Localization Microscopy

 scientific illustration shows Principle of single molecule localization microscopy (SMLM)

Lange Zeit ging man davon aus, dass das Phänomen der Beugung eine unvermeidliche physikalische Grenze für die Auflösung der Lichtmikroskopie darstellt. Nach der Abbeschen Beugungsgrenze können Strukturen, die kleiner als die halbe Wellenlänge des Lichts sind, nicht aufgelöst werden. In den letzten Jahrzehnten gab es jedoch Entwicklungen in der Fluoreszenzmikroskopie, die es ermöglichen, zelluläre Strukturen auf der Nanometer-Längenskala zu untersuchen.

Thinning Out Clusters while Conserving the Stoichiometry of Labeling (TOCCSL)

preview image for TOCCSL

During their random motion, biomolecules experience a manifold of interactions that transiently conjoin their paths. It is extremely difficult to measure such binding events directly in the context of a living cell: interactions may be short lived, they may affect only a minority fraction of molecules, or they may not lead to a macroscopically observable effect. We developed a single molecule imaging method that allows for detecting and quantifying associations of mobile molecules. By “thinning out clusters while conserving the stoichiometry of labeling” (TOCCSL) we can virtually dilute the probe directly in the cell, without affecting the fluorescence labeling of single clusters. 

Protein Micropatterning in the Live Cell Plasma Membrane

Scientific image that illustrates the micropatterning method

© TU Wien

Over the last years we have developed a method, which allows to arrange specific membrane proteins according to micro- or nanopatterns of adjustable size directly in the live cell plasma membrane. Thereby we can generate areas enriched or depleted in the protein of interest within the very same cell membrane. Currently, we apply this method to i) measure biomolecular interactions in the live cell plasma membrane, and to ii) quantify the hydrodynamic size of membrane proteins.