PhD Oral Defense: Molecular characterization of novel glutamate-gated chloride subunits from Schistosoma mansoni

PhD Oral Defense of Vanessa Dufour, Institute of Parasitology.

Flatworms of the genus Schistosoma are wide-spread and clinically significant parasites of humans in the tropics and sub-tropics. Schistosomes exhibit a two-host life cycle, colonize the circulatory system of their definitive host and are dioecious (sexually dimorphic). In evolutionary terms, they are representatives of the earliest metazoans to have evolved separate sexes, and to possess anatomically distinct central and peripheral nervous systems. Schistosome infections are currently controlled by a single drug, praziquantel (PZQ), but the emergence of schistosome strains resistant to PZQ is a growing concern.  A deeper understanding of the basic biology of schistosomes is the first step towards target-based drug discovery, an appealing approach to identify new lead candidates for schistosomiasis control.

The work presented in this thesis focuses on L-glutamate (L-glu) neuronal signaling in S. mansoni. L-glu is an important neurotransmitter in essentially all vertebrate and invertebrate phyla, but its functional roles in S. mansoni are poorly understood. Here, we further contribute to knowledge in this field by providing the first molecular evidence for the contribution of an inhibitory, glutamate-gate Cl^‑ channel (GluCl)-mediated component to glutamatergic neurotransmission in S. mansoni, an unprecedented finding in parasitic flatworms.