Approaches to detect and block transition stages in Trypanosoma brucei

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Studentship strategic priority area:Quantitative Systems Medicine Keywords:Single cell; Trypanosoma brucei; Trajectory inference; cell progression Trypanosomatids are a grouping of single-celled parasites belonging to the order Kinetoplastea. One of these parasites, Trypanosoma brucei, is responsible for the sleeping sickness diseases transmitted by the tsetse fly, affecting humans and livestock in Africa. Only a handful of drugs are available, many of which are not efficient and have severe side effects.Emerging data has explored the factors needed for some, but by no means all, aspects of transmission between the distinct parasites forms found as the parasite moves from mammals to vector and back. Notably, the developmental programme in the tsetse vector is poorly understood and, crucially, little work has examined the temporal order of gene expression changes during life cycle transitions. In this PhD we aim to detect genes essential in the transition from the vector stages to the mammalian stages in T. brucei in order to identify pathways that could be targeted by novel compounds. We will obtain and analyse single cell RNA-seq from these stages. Through pseudo time and branching analysis we will detect genes crucial for transition. Finally, the student will ablate these genes and attempt to block the factors, to ask how they act in the life cycle and test if they might be drug targets. This is an interdisciplinary project to train students in quantitative methods and brings together a supervisor team with a diverse background. By the end of the PhD, the student will have learned novel genomics and laboratory techniques that are crucial in the field of precision medicine.