Molecular genetics of a cell's sense of electric fields. (360G-Wellcome-082887_Z_07_Z)

Directional cell migration plays an important role in development, wound healing and inflammation. There are endogenous wound electric fields and many types of cells, including human cells respond to an electric signal by directional migration (electrotaxis/galvanotaxis). We have pioneered in using a genetic tractable model organism--Dictyostelium discoideum to elucidate the molecular genetics of electrotaxis (Zhao et al., 2002). Based on a successful initial collaboration supported by the Trust , we have developed novel screen strategy and propose to identify molecules and genes important in sensing and responding to an electric signal. We will study systemically the role in electrotaxis of known molecules. This will focus on the molecules critical in chemotaxis, for example: heterotrimeric G-proteins; PI3 kinase / Pten; MAP kinase; small GTPases Ras. This will demonstrate some key sensing and signalling elements sharing or different between chemotaxis and electrotaix. We will in vestigate the role of membrane potential, extracellular ions and ion transportation in electrotaxis. Using our recently developed effective screening strategy, we will isolate strains with defects in electrotaxis from REMI mutagenised and chemically mutagenized cells. This will systemically screen for mutants and identify novel molecule and genes underlying electrotaxis.