Iron starvation response in Trypanosoma brucei, the causative agent of African sleeping sickness

The blood-dwelling parasite Trypanosoma brucei is a pathogen of medical and veterinary importance and in sub-Saharan Africa causes human sleeping sickness and the livestock wasting disease Nagana. To survive within the bloodstream, the parasite must acquire iron from its mammalian host, with the ability to do so being essential for virulence. To prevent the growth of invasive pathogens, mammals limit the availability of essential element iron by sequestering it within the major serum glycoprotein transferrin. To counter this, T. brucei has evolved a unique transferrin receptor that allows it to obtain iron by receptor-mediated endocytosis of host transferrin. The parasite suffers iron starvation when it cannot take up sufficient transferrin from the host bloodstream. To cope with this situation, the parasite responds by rapidly up-regulating the expression of its transferrin receptor, an effect we have shown is mediated by the downstream untranslated region (3’UTR) in the transferrin receptor mRNA transcript (Benz et al. (2018) DOI:10.1371/journal.pone.0206332). As iron acquisition is essential for parasite survival, the discovery of proteins involved in regulating transferrin receptor expression may provide novel targets for therapeutic intervention.

In this PhD project, you will identify and characterise proteins involved in the iron starvation response in T. brucei, and using truncation and site directed mutagenesis identify 3’UTR motifs important for regulating transferrin receptor expression. Selected candidate proteins implicated in the iron-starvation response pathway will be studied using a combination of in situ tagging, inducible RNAi and site-directed mutagenesis, to perturb protein function and examine their role in the iron starvation response. This project will provide excellent training in cell culture, molecular biology, genomics and bioimaging techniques.

Feel free to contact any member of the supervisory team by email at [Email Address Removed] or [Email Address Removed] for further details about the project.

Applications are made by completing an application for PhD Biomedical and Life Sciences October 2019 through our online application system. Closing date: midnight 15th March 2019