Research

Priority Programme “Epithelial intercellular junctions as dynamic hubs to integrate forces, signals and cell behavior” (SPP 1782)

The Senate of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) has established a new Priority Programme entitled “Epithelial intercellular junctions as dynamic hubs to integrate forces, signals and cell behavior” (SPP 1782). The programme will run for an initial period of three years and is extendable to six years.

Epithelia are stable tissues that line organ and body surfaces to provide structural support and serve as barriers against diverse external stressors such as mechanical force, pathogens, toxins, and dehydration. Further, they separate different physiological environments and are instrumental during morphogenesis. These epithelial functions depend to a great extent on the ability of intercellular junctions to sense and integrate mechanical forces and chemical signals. They transmit these into the cell to direct rapid changes in cell architecture and/or transcriptional programming thus directing cellular behavior. Understanding how intercellular junctions sense their neighbours, force and chemical signals, how such information at these junctions is integrated to elicit cellular responses at a mechanistic level will be central to comprehend control of tissue morphogenesis, homeostasis and regeneration. Further, elucidating how genetic defects in intercellular junction components by-pass junction-mediated control of epithelial tissue integrity is a prerequisite to understand the basis of multiple disorders including blistering skin disorders, inflammation and cancer.

The primary goal of the Priority Programme is thus to understand how intercellular junctions sense and respond to mechanical and chemical signals from neighbouring cells and how they convert these signals into processes that underlie epithelial morphogenesis, differentiation and pathogenesis. Participating scientists are expected to study questions with interdisciplinary approaches from the level of molecules to cells, tissues and model organisms, combining biophysical, biochemical, cell biological and physiological techniques.

Projects are directed toward the following goals:

  1. Identification of molecules that sense and transmit mechanical force and chemical signals at intercellular junctions, to get insights into downstream signal transmission
  2. Integration of mechanical and chemical signals by adherens junctions and desmosomes to regulate cell behavior and cell fate
  3. Understanding at a quantitative level how mechanical force is sensed at intercellular junctions and how it is transmitted into chemical signals
  4. Elucidation of the force-dependent crosstalk between intercellular junctions and the cytoskeleton
  5. Advancement of biophysical and imaging methods to analyze force and chemical signaling in tissues