In this talk we focus on signal transduction connecting eukaryotic gradient sensing and polarization in Dictyostelium. We build a modelling framework to describe how particular intracellular components are localized in a steady gradient. However, intracellular components are also polarized as a result of intrinsic processes, including developmental processes, and this has a clear impact on how a cell responds to external gradients. we deal with the issue of how the polarization induced by an external gradient interacts with the intrinsic polarity of the cell. We consider different ways in which the two processes can interact, and do so in a way which incorporates minimal details about the intrinsic process. The modelling of the receptor-mediated pathways involves a description of the PI3K and PTEN pathways and how they regulate the production of phosphoinositide lipids and actin polymerization. We consider the case of a purely additive interaction between the intrinsic and receptor-mediated pathways as well as the case that receptor-mediated pathways inhibit the intrinsic pathways. In each case using systematic computational and theoretical analysis we obtain testable predictions regarding how these processes interact. We also briefly examine the possible role of non-linear dynamical aspects of signal transduction here. If time permits, we discuss some of the implications of these results for cell migration in spatially and temproally varying signals This is work done in collaboration with Pablo Iglesias, Johns Hopkins University.