Laboratory of Integrative Biology


Mechanobiology, cytoskeleton, cytolinkers, cell junctions, simple epithelia

In the past five years, our main research interests have been:

  1. cytoskeleton-dependent regulation of cell-cell contacts in simple epithelia;
  2. regulation of cell-matrix adhesions; and
  3. cytoskeleton and adhesion-mediated signalling in epithelial-mesenchymal transition, cell migration and invasiveness.

We mainly focus on cytoskeletal linker proteins, in particular plectin, and we study the functional consequences of cytoskeletal organization in cell/tissue mechanics and mechanotransduction, i.e., conversion of physical cues into intracellular mechanosignalling pathways. To fulfil our aims in the complexity of biological systems, we use a combination of in vitro (primary cells and CRISPR/Cas9-targeted cell lines) and in vivo (transgenic models) approaches. Besides conventional molecular biology techniques, we also employ methods that enable us to measure and apply physiologically relevant forces and deformations, such as traction force and atomic force microscopy, magnetic tweezer rheology, cell stretching, and FRET-based tension sensors.

As the team of the Laboratory of Integrative Biology was established as part of BIOCEV (in January 2015), our long-term interest is also defined by BIOCEV Project 1.1.4.: „Mouse models for studying of physiology and pathophysiology of digestive epithelia” (the Functional Genomics Programme). This aim has the following core project objectives:

  1. identification of genes with unique and essential functions in simple epithelia;
  2. generation of mouse models with targeted selected genes; and
  3. phenotypic characterization of generated mouse models addressing gene functions in healthy and diseased simple epithelia.
Visualization of biliary tree architecture.
Visualization of biliary tree architecture. (A) Acrylic resin cast of a biliary tree in a liver lobe of adult mouse. Bar, 3 mm. (B) Scanning electron images of bile canaliculi in a wild-type (Plefl/fl; left) and a liver-specific plectin knockout (PleΔalb; right) mouse. Arrowheads, bile canaliculi; asterisk, blind loop in PleΔalb canaliculi only. Bar, 1 µm. (C) 3D spheroid grown from biliary epithelial cells and immunolabelled using antibodies to pan-keratin (green) and plectin (red). Nuclei stained with DAPI (blue). Bar, 10 µm.

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