PhD Oral Defense of Kevin MacDonald, Institute of Parasitology
Schistosomiasis is a debilitating neglected tropical disease that affects hundreds of millions of people in developing tropical and subtropical areas of the world. As a long-term chronic infection, schistosomiasis causes significant annual mortality and morbidity, as well as economic losses. The causative agents of the disease are flatworms of the genus Schistosoma, which are vectored by several snail intermediate hosts into humans. Once inside the human host, schistosomes undergo a complex migratory and developmental period before maturing into adult worms. A key regulator of this process is the parasite nervous system, which controls a variety of essential biological functions in both larval and adult schistosomes. Signal transduction in the nervous system results from the interaction between neurotransmitters and their cognate receptors. In vertebrates, acetylcholine (ACh) is the quintessential excitatory neurotransmitter of the neuromuscular system. In schistosomes, on the other hand, there is evidence that it plays an inhibitory role in parasite motility. This divergence from the vertebrate mode of action suggests that the receptors responsible for mediating this activity may serve as good chemotherapeutic targets. To date, no schistosome cholinergic receptor has been characterized at the molecular level or linked to neuromuscular inhibition. In the present work, we demonstrate the existence of a novel family of schistosome cholinergic receptors that modulate inhibitory neuromuscular responses.