Immune cell signal integration in vivo. (360G-Wellcome-090899_B_09_A)

We will use Drosophila embryonic hemocytes as a model to study cell migration and chemotaxis in vivo. We will initially investigate the dynamic interplay between microtubules and actin in migratory cells as well as further investigating the role of microtubules during contact inhibition and in the maintanence of polarity in hemocytes. In addition to elucidating their cytoskeletal regulation we will explore what external cues direct hemocyte migrations and how their contact inhibitory behaviour is regulated. To this end we will carry out a genome wide-RNAi screen allowing us to identify novel genes required for normal hemocyte dispersal during development as well as their rapid chemotaxis towards epithelial wounds. In addition we will carry out a microarray approach to probe the transcriptome of discrete populations of hemocytes at different developmental timepoints in order to understand the process of hemocyte maturation and specification during development. Finally we also plan t o continue our initial studies using Drosophila embryos as a model system for following bacterial infection in real time. We will test the in vivo function of genes previously identified in RNAi screens in vitro as being important for the recognition, engulfment and degradation of bacteria by S2 cells in culture.