RNA interference (RNAi) is a conserved pathway across all eukaryotic species with a notable exception of some of the parasitic protozoa, including Plasmodium falciparum. On the other hand, protozoan parasites like Toxoplasma, Trichomonas, and Trypanosoma among others retained RNAi, however, with RNAi factors having an atypical domain organization. We are investigating the biogenesis of small RNAs via atypical RNAi factors in an evolutionary context in these clinically important parasites and study small RNA function in the parasite's life cycle, pathogenesis, and host-parasite interaction. In the long term, we would also like to profile the epigenetic landscape of clinical isolates and use our understanding to identify biomarkers for diagnostics and develop intervention methods.