Elucidating the role of Schistosoma mansoni DNA cytosine-methyltransferase (SmDCMT) in regulating Platyhelminth gene expression and development

KF Hoffmann & MJ Wilkinson

Schistosomes are members of a medically important group of parasitic trematodes that contribute to severe morbidity and mortality (200,000 deaths/annum) amongst endemic populations in 74 tropical and sub-tropical developing nations. Large-scale sequencing projects have created extensive schistosome EST and genomic databases leading to the identification of thousands of new genes, as well as providing a repository of information useful for post-genomic activities. In our search for novel chemotherapeutic and immunoprophylactic targets, we have utilised these databases for construction of DNA microarrays to identify developmentally regulated transcripts.   One striking observation from our studies was the sheer amount of differentially expressed transcripts identified. While highly informative at the individual transcript level (identification of novel drug targets and vaccine candidates), global analyses of development signify that regulation of these differentially expressed transcripts is highly complex. Clearly, this indicates that schistosomes, like other metazoans, have distinct (i.e. gender associated, developmentally-regulated?) mechanisms (genetic and epigenetic) to control gene expression. This PhD project will involve a continuation of our current investigations into epigenetic control of schistosome gene expression by specifically focusing on the function of the first Platyhelminth DNA cytosine methyltransferase, SmDCMT (SmGeneDB entry Smp_145390).