This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Schistosomiasis is a disease that affects at least 200 million people worldwide. The causative agent can be one of six different trematode worms belonging to the species Schistosoma. The only treatment that is effective against all 6 species is the drug Praziquantel. Worryingly, there have been a number of reports that schistosomes may be developing resistance to this drug, however, this remains controversial and, as yet, there is no conclusive research that explains how Praziquantel works or how resistance may be acquired. The twin aims of our study are to determine the mechanism of action of Praziquantel and to identify potential new molecular targets against which drugs may be designed. To determine the mode of action of Praziquantel we have to first develop an assay which will accurately determine an accurate sub-lethal dose of the drug for schistosomes. We have accomplished this by identifying a suit of genes that are switched on by relatively high temperatures. When schistosomes are treated with lethal doses of Praziquantel they cannot switch these genes on. We have now determined a sub-lethal dose of Praziquantel and are studying its effect on the expression of schistosome genes using microarrays to help determine its mode of action. In addition, we are also studying the effects of different types of environmental, chemical and immune stress on the schistosomes. This is being done by identifying groups of genes that are switched on or off in response to these stresses. These genes may provide potential new targets for drug design.
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