We have shown that infective larvae of S. stercoralis and other mammalian-parasitic nematodes are attracted to a diverse array of skin and sweat odorants (Castelletto et al., 2014; Lee et al., 2016; Ruiz et al., 2017). Many of the odorants that attract S. stercoralis are also mosquito attractants, suggesting that human-parasitic nematodes and mosquitoes respond to some of the same human-emitted olfactory cues (Castelletto et al., 2014). We are now elucidating the neural and molecular mechanisms that drive odor-driven host seeking in S. stercoralis. We are also now investigating the role of chemosensory cues in driving other parasitic behaviors.
We have shown that infective larvae respond robustly to thermal gradients. When traveling up thermal gradients, infective larvae migrate toward host body temperature. We also showed that targeted mutagenesis of the S. stercoralis tax-4 gene prevents positive thermotaxis, providing the first insights into the molecular basis of host seeking (Bryant et al., 2018). We are now investigating the molecular pathways and neural circuits that drive thermosensory behaviors in S. stercoralis.
Carbon dioxide response
Carbon dioxide (CO2) is a critical host cue for many parasites, including many parasitic nematodes (Banerjee and Hallem, 2020). We have found that both parasitic nematodes and the free-living nematode C. elegans show flexible responses to CO2 such that CO2 can be either attractive or repulsive depending on age, life stage, environmental context, prior experience, or internal state (Carrillo et al., 2013; Lee et al., 2016; Ruiz et al., 2017; Guillermin et al., 2017; Rengarajan et al., 2019). In C. elegans, CO2 response is mediated by the same sensory neuron and a single pathway of downstream interneurons regardless of valence. The CO2-evoked activity of these interneurons is subject to experience-dependent modulation, enabling them to drive opposite behavioral responses to CO2. Other interneurons mediate sensitivity regardless of valence. Thus, the same interneurons contribute to both attractive and aversive responses through modulation of sensory-neuron-to-interneuron synapses (Guillermin et al., 2017; Rengarajan et al., 2019).
Tool development for Strongyloides
We are developing new tools and approaches for studying the molecular and cellular mechanisms that drive host seeking and infectivity in parasitic nematodes. Our understanding of the biology of parasitic nematodes has been limited by the lack of tools for genetic intervention. We developed a method for generating CRISPR/Cas9-mediated targeted gene disruptions in S. stercoralis and S. ratti (Gang et al., 2017; Castelletto et al., 2020). We are now using this system to disrupt a number of different genes to identify signaling pathways that drive host seeking and infectivity. We are also developing other tools for studying neural circuit function in parasitic nematodes.
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