For most organisms, including humans, the whole process of protein synthesis remains remarkably faithful to the original instructions laid out in the DNA. However, unicellular flagellates of the order Kinetoplastida such as trypanosomes developed a highly complex molecular system within their mitochondrion whereby mRNA transcripts are extensively processed. While recent breakthroughs in nuclear genomics have significantly increased our knowledge on trypanosome biology, the true complexity of the mitochondrial genome remains largely uncharacterized. This knowledge gap is especially striking given the fact that key veterinary trypanocidal drugs such as Isometamidium Chloride (ISM) specifically target the mitochondrial genome. Here we hypothesize that ISM drug pressure reduces the complexity and functionality of the mitochondrial genome in drug-resistant Trypanosoma congolense, a parasite with devastating consequences to livestock health and economics in sub-Saharan Africa. This Pump Priming Project will mainly focus on the delivery of a proof-of-concept of a methodology that allows a refined study of the mitochondrial RNA editing dynamics in T. congolense. This methodology will be key for a future full-scale project investigating the impact of ISM drug pressure on small RNA regulation of mitochondrial gene expression in T. congolense, and its consequences for parasite fitness in the mammalian and tsetse fly host.
|Effective start/end date||1/11/17 → 31/12/18|
- Institute of Tropical Medicine Antwerp: €87,997.00
- Vlaamse Overheid: €87,997.00