Whipworm infection – defining and exploiting the niche biology of a parasitic intestinal nematode

Little is known about the mechanisms underpinning chronic infection by intestinal dwelling nematode parasites. If we are to develop novel and effective ways to control these infections and exploit their immune evasion strategies, we require a much deeper understanding of the parasite itself, how it interfaces with its environment and how it survives immune attack during long-term infection. We will address this bottleneck using the Trichuris muris mouse model of human whipworm infection. We will: 1. Define the biology of the major secreted protein produced by whipworm during chronic infection, which we have shown binds interleukin 13 and tethers to glycosaminoglycans and matrix. We will precisely map binding sites, define function in vitro and in vivo and the activity of the human parasite homologue (T. trichiura). 2. Define the tripartite interaction between parasite, host and intestinal microbiota which we have demonstrated is critical to both establishment and survival of the parasite. We will re-colonise germ free mice with Bacteroides thetaiotamicron which effectively supports whipworm infection and plays a major role in scavenging intestinal glycosaminoglycans to identify the key genes of each partner that underpins chronic infection and will test them functionally in vivo to identify novel pathways for intervention.