UC San Diego

Schistosomiasis is a neglected tropical disease (NTD) caused by flatworm parasites belonging to the genus Schistosoma. The disease infects over 200 million people in developing countries where access to clean water is limited. Treatment of schistosomiasis relies on just one drug, praziquantel (PZQ). This drug is only partially effective and resistance is a concern. Together, these encourage the search for new drugs and new drug targets. The proteasome is an essential proteolytic enzyme complex in the cell being responsible for protein turnover. It is a validated drug target for treatment of certain cancers and a promising target for a number of parasitic infections, including Schistosoma. My lab has been using RNA-sequencing (RNA-Seq) to profile the transcriptomic changes after exposure of Schistosoma mansoni to the proteasome inhibitor, bortezomib (BTZ). As part of the aims of my project, I provide an initial characterization of the top 300 gene transcripts that were upregulated after treatment of S. mansoni with 1 µM BTZ after 12 and/or 24 h in vitro. Among these, I identify and discuss heat shock proteins and proteasome subunits that were upregulated at both time points, as well as proteins particular to each time point. Next, using primers that I helped design and then test for efficiency for nine selected genes of interest, I validated the RNA-Seq data via quantitative reverse polymerase chain reaction (qPCR). Lastly, I utilized the Basic Local Alignment Search Tool (BLAST) at the National Center for Biotechnology Information’s (NCBI) website to understand whether particular genes of interest are expressed in other developmental stages of the parasite. The resulting data and analysis offer an initial insight into the transcriptomic response of the S. mansoni after exposure to a proteasome inhibitor with the goal of identifying new drug targets.