Celebration of Scholarship and Creative Activity 2022
Parasitic /Schistosoma/ flatworms cause the disease schistosomiasis infecting more than 200 million people each year. Over 90% of cases occur in the developing world, and the socioeconomic impact is comparable to HIV/AIDS. Parasites are acquired from fresh water containing infectious larva that are released by snail intermediate hosts. Once these worms establish themselves within a human host, they cause significant pathology due to fibrotic scarring of internal organs caused by parasite eggs. The only drug on the market to treat schistosomiasis is praziquantel. This is concerning, since parasites can readily develop praziquantel resistance in the laboratory. Therefore, we are interested in exploring new drug targets and chemical series that can be advanced as praziquantel alternatives. Pentameric ligand-gated ion channels (LGICs) are logical targets to explore given their proven track record in the chemotherapy of other parasites (cholinergics and macrocyclic lactones). This family of channels includes various neurotransmitter receptors such as glutamate receptors (GluCls), GABA receptors (GABAA and GABAρ receptors) and nicotinic acetylcholine receptors (nAchRs). While several schistosome GluCls and nAchRs have been cloned and functionally expressed the majority of LGICs predicted in Schistosoma genomes remain unstudied.