The major function of the proposed research is the functional and molecular characterization of serotonin transport activity in the human blood fluke, Schistosoma mansoni. Serotonin transporters (SERTs) are a major target for antidepressants and psychostimulants, and their importance in mental health necessitates continued efforts to understand the in vivo function and structural biology of these transporters. The parasitic flatworm S. mansoni is a member of the most ancient of the bilateral phyla, and represents a unique model system in which to study serotonin transport. It is hypothesized that flatworm SERT-like proteins are ancient homologues of SERTs from other organisms, and that their cloning and characterization will shed light on the molecular origins and structural biology of more derived SERTs. This hypothesis will be addressed by the molecular cloning of cDNAs encoding flatworm neurotransmitter transporter using homology-based approaches, as well as functional characterization of worm transport activity in situ and in heterologous expression systems. Altogether, it is anticipated that these studies will facilitate the formation of novel hypotheses regarding the structure, function and molecular origins of serotonin transporters, thereby, contributing to existing knowledge of a superfamily of molecules with such importance in human mental health.
