Dysfunction of the neurotransmitter serotonin is implicated in depression, obesity and diabetes. Depression is characterised by a deficit of serotonin neurotransmission. Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed as a treatment to inhibit the serotonin reuptake transporter and boost synaptic serotonin levels, alleviating depression.
The specific mechanism of these antidepressants is increasingly ambiguous and the molecular targets of these drugs remain unknown. In order to understand the molecular and cellular targets of such antidepressants in humans we will use both genomic and genetic approaches with the nematode Caenorhabditis elegans as a model system. This knowledge will facilitate the design of new and better drugs for treating depression and related disorders.
As serotonin is important in regulating metabolic control we expect that SSRI targets may also be important in regulating metabolic pathways. One such pathway in C. elegans controls the formation of a resistant life stage called the dauer juvenile in response to adverse environmental conditions. Serotonin has been shown to suppress dauer formation.
We propose to examine its role and the effect of SSRIs on the dauer pathway. Knowledge of genes playing a role in processing cues for entry into or exit from this state of diapause could be easily applied to other species. Many animal parasitic and the economically important insect parasitic nematodes are transmitted by an infective juvenile which is an arrested life stage similar to the dauer juvenile.
This study would be important in understanding parasite life cycles and may also provide ideas to study the effects of serotonin on human metabolism. A primary aim of this project is to train a young nematologist in molecular biological technology and approaches developed in C. elegans relevant to serotonin signalling.
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