We seek an enthusiastic student with experience in parasitology or pathology for an exciting four year Ph.D. studentship to study tissue distribution and metabolic adaptation in African trypanosomiasis.
African trypanosomes cause substantial disease in humans and livestock. Livestock disease is caused by the genetically and phenotypically distinct species, Trypanosoma brucei and T. congolense [1]. These parasites differ in their pathology, and this is very likely linked to the way they interact with and distribute within their host. T. brucei is characterised as an extravascular parasites, disseminating into tissues, whereas T. congolense is an intravascular parasite, remaining within and adhering to blood vessels. While these differences have been analysed in vitro and in the mouse model [2], we know very little about how these phenotypes manifest and cause pathology in the clinically relevant bovine host [3]. Additionally, existing in particular niches in the mammalian host is predicted to impact upon parasite biology, including metabolism, as they adapt to particular environments. The student will use cutting edge techniques to analyse and map parasite distribution in bovine host tissues, including immunohistochemistry and microscopy, to generate a tissue atlas for T. congolense and T. brucei in cattle. The student will also aim to isolate parasites from particular tissues, as well as analysing parasites in situ, and use RNAseq, metabolomics and spatial proteomics, in order to characterise metabolic adaptation to tissue residence. Identified pathways will then be perturbed by genetic modification, and impact on tissue adaptation tested in the mouse model.
This project will utilize in vitro as well as in vivo cattle and mouse African trypanosome infection models that are available in the supervisors’ laboratories. The project brings together several important biological disciplines, including parasitology, pathology and polyomics, including cutting edge approaches. This will provide the student with excellent training opportunities in the following important transferable skills: in vivo biology; pathology; state-of-the-art bio-imaging; cell culture; transcriptomics, metabolomics and proteomics.
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