Investigation of posttranslational histone modifications and co-regulators of expression in the Schistosoma mansoni stages

Abstract

Schistosomiasis is caused by the parasite Schistosoma mansoni and is prevalent in tropical and subtropical areas of the world. It is estimated that it affects 200 million people and more than 1,53 million people are disabled by the disease. S. mansoni presents a complex life cycle with an intriguing development and although several efforts have been made to study genes, transcripts and epigenome of the parasite, little is known about how gene expression is regulated. In the attempt to understand the control of the gene expression in the life cycle of the parasite, the aim of this project is to investigate the importance of posttranslational histone tail modifications and whether these epigenetic marks are dynamically acquired and lost during stages as well as the putative transcriptional co-regulators that contribute to the gene expression control of the parasite. Specifically, it is proposed to investigate: 1) the dynamics of chromatin modification using mass spectrometry; 2) elaboration of a comparative map between histone PTMs and gene expression of annotated modifying enzymes in the stages; 3) putative transcriptional co-regulators such as HP1 that may play a role in the regulation of silencing in cercariae. Finally, with this project we can advance in knowledge on the regulation of different parasite stages gene expression and may find new strategies to treat this disease. (AU)