IMPACT OF DYNAMICS AND SPATIAL ORGANIZATION OF SIGNALLING MOLECULES/ACTIVITIES ON CELL PHENOTYPE
Prof. Dr. Philippe I.H. Bastiaens
Director of the Department of Systemic Cell Biology at the Max Planck Institute of Molecular Physiology in Dortmund and Professor of Cell Biology and Biochemistry in the Department of Chemistry and Chemical Biology at the University of Dortmund
Cell Biophysics Laboratory at the Imperial Cancer Research Fund, London, UK
Cell Biology and Biophysics program at the European Molecular Biology Laboratory and Professor at the University in Amsterdam
Department of Biochemistry at the University of Wageningen
Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
Department of Biochemistry, University of Wageningen, The Netherlands
Cellular information processing is traditionally explained by unidirectional causalities between activities of gene products; the so-called signal transduction pathways. Since the inception of the department in 2007 we have taken a different road to investigate how cells process extracellular information by studying how the spatial organization of signaling molecules emerges from their collective dynamics and how this in turn affects cellular response. From this endeavor we came to the conclusion that signal transduction cannot be perceived as originating from a hardwired circuitry, but more as a highly adaptive network that obtains its properties by recursive interactions between biochemical activities of the network itself as well as with the networks of other cells by extracellular communicating factors. In this way the processing of information of the network becomes dependent on historical and extracellular context. We therefore like to think about signaling as a process more reminiscent to cognition. We experimentally and theoretically study properties of biochemical cognitive networks embedded in systems of different scales and context, from reconstituted artificial cells, to tissue culture cells, to cellular assemblies such as organoids.
The approaches in the Department of Systemic Cell Biology are necessarily highly multidisciplinary and range from 1) the development of new single molecule and functional microspectroscopic techniques to image dynamics and spatial patterns of molecular processes, 2) over chemical-biological and genetic tools to observe and perturb intracellular networks, 3) to bottom-up biochemical reconstitution approaches, and 4) computational modeling and non-linear dynamics to derive and conceptualize physical principles that underlie the dynamics of signaling and self-organization of living matter.
• Functional microscopic imaging approaches (e.g. Fluorescence Lifetime Imaging to measure FRET,
Fluorescence Correlation Spectroscopy, Selective Plane Illumination Microscopy, Single Molecule Imaging,
Total Internal Reflection Microscopy, Cryo-microscopy…)
• Electron microscopy
• Generation of biosensors for measuring protein activities in living cells
• Development of advanced microscopy techniques and data analysis approaches
• Simulation approaches for understanding reaction networks in living cells
Masip ME, Huebinger J, Christmann J, Sabet O, Wehner F, Konitsiotis A, Fuhr GR, Bastiaens PI. Reversible cryo-arrest for imaging molecules in living cells at high spatial resolution. Nat Methods 2016, Jul 11. doi: 10.1038/nmeth.3921.
Schmick, M., Bastiaens, P.I.H. The interdependence of membrane-shape and signal processing in cells. Cell 2014, 156(6):1132-1138. Review.
Schmick M, Vartak N, Papke B, Kovacevic M, Truxius DC, Rossmannek L, Bastiaens, P.I.H. KRas Localizes to the Plasma Membrane by Spatial Cycles of Solubilization, Trapping and Vesicular Transport. Cell 2014, 157(2):459-471.
Zimmermann G, Papke B, Ismail S, Vartak N, Chandra A, Hoffmann M, Hahn SA, Triola G, Wittinghofer A, Bastiaens PI, Waldmann H. Small molecule inhibition of the KRAS-PDEd interaction impairs oncogenic KRAS signalling. Nature 2013, 497(7451), 638-42.
Chandra A, Grecco HE, Pisupati V, Perera D, Cassidy L, Skoulidis F, Ismail SA, Hedberg C, Hanzal-Bayer M, Venkitaraman AR, Wittinghofer A, Bastiaens PI. The GDI-like solubilizing factor PDEd sustains the spatial organization and signalling of Ras family proteins. Nat Cell Biol 2012, 14(2), 148-58.
Grecco HE, Roda-Navarro P, Girod A, Hou J, Frahm T, Truxius DC, Pepperkok R, Squire A, Bastiaens PI. In situ analysis of tyrosine phosphorylation networks by FLIM on cell arrays. Nat Methods 2010, 7(6), 467-72.