Elucidating mechanisms of iron regulation in an ancient eukaryote, Trypanosoma brucei

If you are interested in joining the seminar, please contact: vseminars@mpiib-berlin.mpg.de

Once registered, you will receive a zoom conference link 30 mins before the talk starts - please sign in using your full name.

Talk abstract:
Iron is an essential nutrient for almost all living organisms. Its restriction by host cells (also known as nutritional immunity) is an elegant strategy to limit pathogenicity of invading pathogens. The underlying mechanisms for such evasion are well studied in standard model systems but poorly understood in Trypanosoma brucei, divergent eukaryotic parasites of humans and livestock.

We have applied transcriptomic and proteomic approaches and identified a cohort of trypanosome-specific genes whose expression levels increase during iron starvation, including the first iron responsive RNA binding protein (RBP5). Here, we report on their mechanism and kinetics of activation. We identified a cis-acting iron responsive element in the 3’ untranslated region of RBP5 and show that sustained overexpression of RBP5 facilitates lifecycle transitions during an infection. Overall, our data show that the mechanisms for iron uptake and intracellular regulation in trypanosomes have diverged significantly from their hosts, indicative of a non-canonical mechanism for iron regulation that can be exploited for anti-trypanosome therapies.

Our group also studies whether sequence polymorphisms in iron transporters contribute to disease transmission. We have collected trypanosomes from 240 livestock in the field (in Accra, Ghana) and found that the predominant circulating trypanosome species was T. brucei with predominant infections of sheep. Our study highlights the need to pay attention not only to cattle but also to other domestic animals when implementing control measures for elimination of trypanosomiasis. We are using next generation sequencing to study the evolutionary diversity of one iron import protein the transferrin receptor to understand whether polymorphisms in this gene enable trypanosomes to expand their host reservoirs.