A feature of many current compounds having nematostatic or nematocidal activity is that they are activators of ion channels. We discovered that a serotonin-gated chloride, that appears to be phylogenetically restricted to nematodes, may be required for root invasion behaviour in plant parastic nematodes. To screen for novel and selective channel activators of this serotonin-activated channel we devised a screening method that makes use of the free living nematode Caenorhabditis elegans for heterologous expression. In this approach the serotonin-gated ion channel from the parasitic nematode Globodera pallida has been selectively and specifically expressed in a single neuron of the C. elegans pharyngeal nervous system, M4. This neuron plays a critical role in C. elegans development. We have shown that exposure of C. elegans expressing the G. pallida serotonin-gated chloride channel in M4 to serotonin during development leads to larval arrest. This may be explained by a scenario in which heterologous expression of the serotonin-gated chloride channel in M4 confers sensitivity of the pharyngeal system to silencing by exogenous serotonin. We have developed this into a whole organism fluoresence based binary screen using C. elegans larval arrest to detect potential modulators of the G. pallida serotonin-gated chloride channel as a route to characterise a novel pharmacophore for nematode control.

Target-based binary screen for novel nematicides

ACS Fall 2021

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