D A Horton3; R Torres Pereira3; H D Arican-Goktas3; P Driguez2; G Rinaldi2; M Knight1; J Bridger3;
1 George Washington University, United States; 2 Wellcome Trust Sanger Institute, UK; 3 Brunel University London, UK
We have previously demonstrated that in the interphase nuclei of the intermediate snail host,
Biomphalaria glabrata, specific genes, such as the (Heat shock protein) Hsp70 loci are relocated
rapidly to new non-random nuclear locations with minutes of the presence of Schistosoma mansoni
parasites. This relocation is correlated with the subsequent upregulation of the gene in susceptible
snails, which is not apparent in resistant snails or in susceptible snails that have been exposed to
irradiated attenuated parasites (miracidia).
This active and functional relocation of the Hsp70 loci can be recapitulated by heat-shocking snails at
32oC. However, in aged snails the gene loci relocation is not possible neither in the presence of
parasite nor heat-shock. We have evidence to support that the rapid relocation of gene loci is due to
the presence of nuclear motor activity in young snails which is lacking in aged snails. Interference
with this mechanism negatively affects chromatin dynamics and gene expression in response to an
infection or a heat shock stimulation. This lack of chromobility recapitulates a recent finding in aged
human cells (senescent) that normal nuclear motor activity for rapidly relocating chromosomes is
also lacking, making B. glabrata a new model organism in which to study genome behaviour in
relation to ageing.
Since we know this gene movement and subsequent upregulation of gene expression are involved in
an active schistosome infection, we hypothesis that aged snails would be less able to be infected by
S. mansoni, making this nuclear motor complex and dynamics mechanism a target with respect to
controlling infection of this human parasite in the snail.