Molecular Mechanisms of Intracellular Trafficking

Research Strategy

The precise regulation of secretory and endocytic trafficking is inevitable to ensure cellular homeostasis and to prevent a disease. In order to identify novel regulators, we have developed a number of cell assays and techniques to facilitate functional genetic screens in collaboration with the group of Holger Erfle at BioQuant. Numerous novel trafficking regulators, including ncRNAs, were identified. Based on this data pool, we decided to proceed in two directions with projects in both basic and applied research. Firstly, we continue to analyze endocytosis of integrins, which are the major receptors for the interaction of cells with the extracellular matrix. We aim to understand how information about cell shape, differentiation status, and adhesive properties of the surrounding defines integrin trafficking routes. Secondly, in the applied research project, we investigate how the functional and morphological features of the endocytic machinery influence cargo internalization and release.

We will extend our research in the two chosen directions. Multiple pathways of integrin entry, recycling, or degradation operate in the same cell, indicating an adaptive system that responds rapidly to a variety of chemical and physical stimuli. We harness multicolor live cell assays, gene silencing, and single-cell imaging to identify regulatory principles for decision-making in health and disease. Deregulation of integrin trafficking in vascular pathologies is being investigated in collaboration with Michael Keese (Medical Faculty Mannheim, Heidelberg University). In the second project, we aim to enhance endocytosis-based targeted cargo delivery in 3D cell cultures with the partners of the “3DTransfect” project at BioQuant. Furthermore, the targeted transfection of endonucleases for gene silencing applications will be optimized in the frame of an EMBL-associated research program at the EMBL-Vilnius University partnership institute for Gene Editing Technologies.