Unravelling novel molecular mechanisms of iron-sensing in African trypanosomes

Every organism requires iron as an essential nutrient for survival. In mammals, iron is sequestered by a protein called transferrin and imported into the cell by the transferrin receptor. When iron levels are low, iron-sensing RNA-binding proteins bind iron-regulatory RNA elements to increase transferrin receptor expression. Intracellular iron-regulatory processes have been studied in many organisms, but not extensively in parasitic trypanosomes that infect humans and animals.

Using global comparative RNA-sequencing data under iron-starved and iron-sufficient conditions, I have identified novel parasite-specific genes acting in this pathway. I aim to study the function of these genes using targeted deletions and/or overexpression. I will use proteomic approaches to systematically map the network of proteins and the pathway(s) that sense and respond to iron starvation in trypanosomes.

Identification of differences in iron-stress response pathways between mammalian host and trypanosome parasites can direct future drug design and improve treatments.