Discovering New Schistosome Drug Targets: The Role of Transcriptomics

Abstract

Microarrays are a platform resource that allow the analysis of the entire transcriptome profile of an organism. New advances in the design and production phases make microarrays the perfect tool for parasitology. The mode of action of many drugs employed to treat parasitic diseases are not understood and coupled with rising concerns of drug resistance, all emphasises the importance of research into the interactions drugs have on their target transcriptomes. One particular disease schistosomiasis, relies on a limited number of chemotherapies for treatment and is a prime example of the need for detailed gene expression information while under drug pressure. Recent microarray studies investigating the basic biology of the major species of Schistosoma and their associated microarray platforms, have provided the basis for future drug mode of action/ drug resistance studies. However determining what is a direct gene expression change due to drug treatment is a hurdle that must be addressed both at the level of parasitology and general toxicology. The utilisation of time-course and/or drug concentration studies, and generic stress inducers, in combination with advanced statistical/bioinformatical methods will allow the separation of direct, indirect and generic gene expression responses. It is hoped that with these approaches the future investigation of complex biological and physiological questions such as drug mode of action or drug resistance in parasitology may be addressed.

Schistosomiasis in the People's Republic of China: the Era of the Three Gorges Dam

“…The landmark availability of the complete sequences of the S. japonicum (171) and S. mansoni (18) genomes will provide the necessary ancillary information. As well, new approaches in antigen discovery through the generation of a large schistosome transcriptome database, gene finding, and the explosion in postgenome technologies, including DNA microarray profiling, proteomics, glycomics, immunomics, and the application of RNA interference (RNAi) and novel imaging techniques (2,24,25,41,53,72,73,75,76,85,95,109,126,127,179,189,197,205,219,224,230), provide an unprecedented opportunity to identify a new generation of vaccine target molecules that may induce greater potency than the current candidate schistosome antigens (138).…”

Organ‐Specific Distributions of Lysophosphatidylcholine and Triacylglycerol in Mouse Embryo

“…The techniques of metabolomics [1], proteomics [2,3], and transcriptomics [4,5] have been used for detailed analyses of metabolites, proteins, and RNAs. In these techniques, distributional information for the biomolecules of interest is lost due to the homogenization during sample preparation.…”

Development of “-omics” research in Schistosoma spp. and -omics-based new diagnostic tools for schistosomiasis

“…After the obtainment of numerous ESTs data, microarray and serial analysis of gene expression (SAGE) technology have been used to profile the transcripts of schistosomes in different stages and/or under distinct conditions. In particular, Geoffrey Gobert classified these transcriptomics applications into four main categories (Gobert, 2010), i.e., (a) characterizing individual cell/tissue types, (Jones et al, 2007; Gobert et al, 2009a), (b) profiling the intact organism and lifecycle (Hoffmann et al, 2002; Fitzpatrick et al, 2004, 2005, 2009; Hoffmann and Fitzpatrick, 2004; Chai et al, 2006; Dillon et al, 2006, 2008; Gobert et al, 2006, 2009b; Moertel et al, 2006; Vermeire et al, 2006; Jolly et al, 2007; Ojopi et al, 2007; Williams et al, 2007; Hu et al, 2009; Taft et al, 2009), (c) parasite–host interactions and effect of therapies on parasite (Hoffmann et al, 2001; Alger and Williams, 2002; Sandler et al, 2003; Aragon et al, 2008, 2009; Gobert and Jones, 2008; de Moraes Mourão et al, 2009; You et al, 2009; Burke et al, 2010; Gobert et al, 2010), and (d) gene expression differences between geographical isolates or species (Le et al, 2002; Fitzpatrick et al, 2004; Moertel et al, 2006). Not until 2012 was the transcriptome of the adult and egg stages of S. haematobium profiled along with its genome (Young et al, 2012).…”