Ascaris infection, a prevalent neglected tropical disease, affects around 819 million people worldwide and causes significant economic losses in the livestock (e.g. Pig) industry. Despite available anthelmintics, reinfection and emerging drug resistance are major concerns. Targeting the early stages of infection, specifically hepatopulmonary migration (HPM), where larvae migrate from the intestine to the liver and lungs, probably guided by chemosensation, presents a promising intervention strategy. However, our understanding of chemosensation in parasitic nematodes is still limited.
In my thesis, I explored into the role of chemosensation in guiding larval Ascaris suum during infection. To support study of chemosensory signaling in Ascaris migration, I utilized comparative genomics, and phylogenetics to curate putative chemosensory genes in Ascaris. I have conducted tissue-specific transcriptional studies, identifying a chemosensory pathway specifically present in the head and amphidal (chemosensory) tissues of Ascaris. Subsequent larval migration assays demonstrated the chemotactic responses to fresh pig liver and lung homogenates, as well as extracted metabolites. Transcriptional profiling of the stimulated larvae highlighted the molecular pathways involved in Ascaris chemotaxis. Additionally, we fabricated (with our collaborator from RMIT university) and characterized a polydimethylsiloxane (PDMS) microfluidic device to further investigate the chemosensory behaviour of Ascaris larvae. Our findings in microfluidics study revealed distinct behavioural responses of larvae to linear concentration gradients and confirmed chemoattraction to pig liver homogenates, demonstrated by increased forward speed and reduced turning. Future studies will aim to identify target-receptor interactions to potentially block chemotaxis and disrupt HPM.