9 - Mechanisms of downstream signalling
from the Rho GTPase network to cell morphogenesis and cell motility

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 642866.

Universität Duisburg-Essen (UDE) - Germany

Supervisors: Perihan Nalbant, Leif Dehmelt

Student: Rutuja Patwardhan

We will study how cytoskeletal effectors such as formins are spatially and temporally controlled by Rho GTPase networks and how this is translated into dynamic reorganisation of the actin cytoskeleton and force generation. Microscopy-based measurements of cytoskeletal dynamics Rho GTPase activity, local effector recruitment dynamics, force transduction and cell shape changes will enable analysis of their spatio-temporal correlation. We will combine those experiments with acute or long-term Rho GTPase perturbations via photo-activation, small molecule dimerisers or RNAi to investigate the underlying molecular mechanisms. In particular, we will focus on the influence of matrix elasticity  on GTPase-effector signalling by measuring the spatio-temporal correlation of stress fibre and focal adhesion turnover with Rho GTPase activities and effector recruitment, as well as tyrosine kinase signalling downstream of integrins. Small molecule inhibitors of related kinases and phosphatases will be applied and optimised (NTRC) to interfere with disease relevant processes, such as cancer metastasis. Computational modelling will be used to integrate these measurements into a comprehensive framework for predictive simulations.