Leishmania is a protozoan parasite with a remarkable tolerance for aneuploidy, while this phenomenon is often deleterious in other organisms. The result of aneuploidy is that all genes of an affected chromosome have an altered gene dosage (i.e. more or less copies) compared to the euploid situation. In Leishmania, we have previously shown that the majority of transcripts and proteins follow dosage changes in a same in vitro condition, while for the remaining products dosage compensation occurs by an unknown mechanism. This project investigates whether (i) dosage compensation occurs by alterations of transcript stability, translation efficiency and/or protein stability, driven by specific transcript and protein biomolecular features and (ii) whether dosage compensation regulation is modulated during the life cycle. As such, we will determine the relative contribution of each regulation layer to the overall compensation and establish a conceptual model of dosage compensation in Trypanosomatids. This is the first integrated multi-omic of dosage compensation in Leishmania, but also in Trypanosomatids in general. The study will lead to novel insights in how this compensation is regulated in aneuploid cells, and investigate if this has a life-stage specific component to it. These fundamental mechanisms are still incompletely understood in all eukaryotes and trough this study, we believe it is possible to gain insights in potentially hitherto unrevealed regulatory mechanisms in eukaryotes.