An epigenetic switch: how to make a parasite

Parasitic nematodes are important parasites of humans and animals. Parasitic nematode life cycles switch between free-living stages and parasitic stages, when they turn on a parasitism gene expression programme. But how parasitic nematodes control this switch in their gene expression is unknown and what we will investigate. Free-living nematodes use large, stable chromatin domains and small RNAs to control their gene expression. We hypothesise that parasitic nematodes also have large chromatin domains but (unlike free-living nematodes) that these change during their life cycle, and that these integrate with sRNAs to control parasitism gene expression programmes. We will study the parasitic nematode Strongyloides whose life cycle is ideally suited to this work, and where there are genomic clusters of parasitism genes. We will compare chromatin domains, small RNAs and gene expression between parasitic and free-living stages to understand how the expression of the parasitism clusters is controlled. We will also investigate how chromatin domains and small RNAs epigenetically control early larval parasitic vs. free -living fate. By understanding this we can learn how to switch off parasites' parasitism programmes and so stop them being parasites, thus developing a new approach to reduce the burden of nematode infection in vulnerable human populations.