Authors
D A Horton1; G Rinaldi3; P Driguez3; H D Arican-Goktas1; M Knight2; J M Bridger1; 1 Brunel University London, UK; 2 George Washington University, United States; 3 Wellcome Trust Sanger Institute, UK Discussion
The spatial organisation of the genome of the interphase nuclei is highly regulated, with chromosomes and genes occupying specific regions of the nuclei to which they can be reproducibly localised. However, when cells react to sudden changes in their environment, i.e. when they are exposed to external stimuli, genes and/or whole chromosomes can be actively and rapidly relocated, this mechanism is associated with regulating of gene expression. We have shown that Schistosoma mansoni, a blood fluke that infects a quarter of a billion people globally, induces this mechanism in its intermediate snail host Biomphalaria glabrata. Subsequent gene repositioning is followed by upregulation of gene expression, which seems to be necessary for infection establishment. In particular, heat shock protein 70 (hsp70) locus which has been shown to relocate in susceptible but not resistant strains of B.glabrata when exposed to the parasite, can also be induced to move by heat shock making B.glabrata an invaluable model for exploring the mechanisms behind gene migration. We now have evidence that B.glabrata nuclear myosin is required to permit the movement, as inhibition of nuclear myosin blocks gene movement in the heat shock model. Understanding the mechanisms behind this parasite induced relocation and subsequent gene upregulation through nuclear signalling, chromatin remodelling and chromatin dynamics will allow us to uncover the complex co-evolved host-parasite relationship with the main goal of discovering novel strategies for infection control. 
