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Our primary goal is to use molecular & integrated “omics’ approaches to study
the regulation of intracellular iron homeostasis in the African trypanosome, Trypanosoma brucei
Intracellular iron regulation
Trypanosomes live extracellularly in blood where they interact with their host obtaining essential micronutrients such as iron for survival.
Iron is a critical co-factor for numerous important reactions in both eukaryotes and prokaryotes, but in the presence of oxygen iron can be very toxic - creating the need for very tight regulation of free iron levels.
In mammalian cells this regulation is achieved by iron regulatory proteins (IRP e.g. aconitase) containing iron-responsive elements (IRE) that control expression of major components of the iron acquisition pathway such as the transferrin receptor (TfR) - see (A).
However, how this task is achieved in African trypanosomes is completely unknown (B). Interestingly, African trypanosomes have a surface protein that functions as a transferrin receptor (TfR), and expression levels of this protein is also modulated by iron availability. However, TbTfR is structurally distinct from the mammalian TfR, and previous work indicates that T. brucei lacks the canonical IRP/IRE iron-based regulatory system.
Our research will seek to understand if trypanosomes have co-opted alternative eukaryotic mechanisms for iron-sensing and regulation of iron homeostasis under three broad themes.
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