EXPRESSION PROFILING OF DEFENSE AND STRESS RELATED GENES OF SCHISTOSOMA MANSONI

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 血吸虫病是一种影响全世界至少2亿人的疾病。病原体可能是属于血吸虫属的六种不同蠕虫之一。对所有6种物种有效的唯一治疗方法是药物吡喹酮。令人担忧的是，已经有一些报告说，药物可能会对这种药物产生耐药性，然而，这仍然存在争议，到目前为止，还没有结论性的研究来解释吡喹酮如何工作或如何获得耐药性。我们的研究的双重目的是确定吡喹酮的作用机制，并确定潜在的新的分子靶点，针对这些靶点设计药物。为了确定吡喹酮的作用模式，我们必须首先开发一种测定方法，该方法将准确测定药物对溶酶体的准确亚致死剂量。我们已经通过识别一套由相对较高的温度开启的基因来实现这一点。当染色体被致死剂量的吡喹酮处理时，它们不能启动这些基因。我们现在已经确定了吡喹酮的亚致死剂量，并正在使用微阵列研究其对染色体基因表达的影响，以帮助确定其作用模式。此外，我们还在研究不同类型的环境、化学和免疫应激对染色体的影响。这是通过识别基因组来完成的，这些基因组在对这些压力做出反应时被打开或关闭。这些基因可能为药物设计提供潜在的新靶点。

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.