Project 1: Interdisciplinary investigations of the mechanisms of collective chemotactic cell movement in Dictyostelium

Guided collective cell movement is an essential process during development and when misregulatedresults in congenital defects and disease. We investigate collective cell movement during the multicellular development of the social amoebae Dictyostelium discoideum an established genetically tractable model system for the study of chemotactic cell movement. We study how dynamic gradients of chemo-attractant cyclic AMP are generated and detected by cells and translated into a stable polarisation of the actin myosin cytoskeleton to result directed cell movement up the gradient. We use a combination of advanced proteomic (SILAC) and molecular genetic (knockin/knockout) techniques to identify critical components of the signalling pathways to the cytoskeleton and to make and characterise mutants in these components. The mutant characterisation involves advanced live cell imaging of GFP tagged components using TIRF and multi-photon confocal imaging as well as biophysical measurements to measure forces produced by migrating cells in combination with mathematical and computer modelling.