Microfluidic In Situ Sequencing for revealing Signaling Transduction in Organoids

Dr. Matthias Meier (IMTEK, University of Freiburg)

One of the most prevailing questions within the field of cell signaling research is: Do the results obtained from model cell lines in artificial environments resemble the dynamics of cell signaling in multicellular tissue and organisms. Cells embedded in three-dimensional (3D) tissue have been shown to receive mechanical signals from cell-to-cell contacts and the extracellular matrix. The mechanical properties of the cell microenvironment alter cell size, growth, proliferation, and/or gene expression and thus not taken into account in 2D cell cultures. In this BIOSS funded project we developed a microfluidic chip technology for culturing and stimulating 3D organoids. Cells in organoids are connected by tight junctions and extracellular matrixes, which resembles the natural mechanical tissue environment. In order to observe signal transduction within the organoids we will apply optical clearance method for deep tissue imaging. Combination of microfluidic technology and optical clearing should allow to analyze in situ changes of protein interactions.