Objective
Whipworms (Trichuris trichuira) are soil-transmitted helminths that infect about 700 million people in the tropics
and sub-tropics and cause the human disease, trichuriasis. Whipworms live preferentially in the cecum of their
hosts where they tunnel through epithelial cells and cause inflammation potentially resulting in colitis. Despite
extensive research, the role of whipworm interactions with epithelial and immune cells in triggering parasite
expulsion remains unclear, hindering the development of anti-parasite therapies. The ultimate goal of my research
proposal is to investigate and understand this interaction in detail. To achieve this, I will use T. muris, a mouse
model of T. trichuira infection in humans. This research proposal has three key aims. First, to identify new parasite
and host genes that could interplay and modulate immunological outcomes. Second, to characterize the role of host
genes in whipworm infection and immunity. Here, novel and known candidate mutations conferring susceptibility
to colitis identified through the Wellcome Trust Sanger Institute - Mouse Genetics Project will be targeted. Thus, I
will challenge mutant mouse lines with T. muris and evaluate the influence of these mutations on anti-parasite
immunity and expulsion. Finally, upon identification of key genes regulating the immune response to whipworms, I
will explore the mechanism of action of selected genes and their effect on the parasite. For this, I will take
advantage of the vast range of ‘omic’ technologies and facilities available at the WTSI. This project will generate
novel fundamental data on host-whipworms interactions and also support future efforts to control these parasites by
the identification of potential new therapeutic targets. Moreover, resulting knowledge of the parasiteimmunological
interplay could be exploited to understand other intestinal inflammatory diseases such as ulcerative
colitis that have many similarities with trichuriasis.
Fields of science
- medical and health scienceshealth sciencestropical medicine
- medical and health scienceshealth sciencesinflammatory diseases
- medical and health sciencesclinical medicinegastroenterologyinflammatory bowel disease
- medical and health sciencesbasic medicineimmunology
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccines
Programme(s)
Funding Scheme
MSCA-IF-EF-ST - Standard EFCoordinator
CB10 1SA SAFFRON WALDEN
United Kingdom