Tracking of Phosphoinositide Pools - Key Signalling Components in Cell Migration and Polarisation (TraPPS)
Membrane dynamics modulate cell polarity, vesicular trafficking, migration, growth, proliferation, differentiation, and more. Of all membrane lipids, phosphoinositides play a central role in these processes. Although a role for the prominent 3-phosphorylated phosphoinositides such as PtdIns(3,4,5)P3 and PtdIns(3)P has been highlighted in physiology and disease, dynamics and localization of these lipids are still poorly understood. TraPPs will provide a dynamic and refined view of phosphoinositide flux, and required lipid modifying enzymes, e.g. PI3Ks, lipases, and lipid phosphatases.
Lipid-modifying enzymes will be targeted dynamically to distinct cellular locations, and lipid-interacting proteins shall be manipulated to display their free or lipid-bound state. Activation of lipid modifying enzymes will be linked to localized upstream signalling and specific cell responses. Cellular, genetic fly and mouse models will be used to validate the uncovered molecular mechanisms. This project provides the basis for a broader systems biology approach of lipid signaling, and will elucidate dynamic cellular processes relevant to cancer and inflammation.
Project Leader:
Professor Matthias Wymann, University of Basel, Switzerland
Principal Investigators:
- Professor Karl-Eric Magnusson, University of Linköping, Sweden
- Professor Carsten Schultz, European Molecular Biology Laboratory , Heidelberg, Germany
- Professor Harald Stenmark, The Norwegian Radium Hospital , Oslo, Norway
- Professor Theodorus Gadella, Molecular Cytology University of Amsterdam, Netherlands
Associated Partners:
- Professor Edwin Constable, University of Basel, Switzerland
- Professor B. Christoffer Lagerholm, University of Southern Denmark, Odense, Denmark
- Professor Markus R. Wenk, National University of Singapore, Singapore
