Discussion

Schistosomes infect over 200 million people and are one of the leading causes of morbidity and disability in developing countries. These helminths have a complex life cycle that involves a clonal stage in the snail host, a sexually-differentiated stage in the mammal host and dramatic transitions between free-swimming and parasitic stages. There is indirect evidence that post-transcriptional regulation is responsible for controlling some of these changes over the parasite life cycle. For example, transcription is halted in the cercarial stage and despite no initial increase in mRNA transcription after transformation into schistosomulum, protein synthesis expands. It is not known if protein translation is regulated via mRNA sequestration, ribosome pausing or other mechanisms. In addition, current proteomics methods are not yet sensitive enough to detect all proteins synthesised during stages of the schistosome life cycle. To address these deficiencies we have commenced the first ribosome profiling studies in the schistosomes. Our first ribosome profiling libraries, using a ligation-free method across a broad range of S. mansoni life cycle stages, have footprints that map well to the CDS region, show codon periodicity, and correlate with published RNA-seq studies. Our next step will be to closely examine the cercaria-schistosomulum and miracidium-sporocyst transitions at the mRNA, ribosome footprint and protein levels using RNA-seq, ribosome profiling and quantitative proteomics (LC-MS/MS with TMT labelling). In addition, using a similar approach, we are also examining differences between male and female adult worms and the regulation of clock genes in a circadian rhythm study. Once better understood, post-transcriptional regulators or stage critical proteins could make attractive drug and therapeutic targets for schistosomiasis.