Biological insights into the parasitic nematode Heligmosomoides bakeri from bulk and single-cell transcriptomics

Pollo, Stephen Michael Jerome

Biological insights into the parasitic nematode Heligmosomoides bakeri from bulk and single-cell transcriptomics

dc.contributor.advisor	Wasmuth, James
dc.contributor.author	Pollo, Stephen Michael Jerome
dc.contributor.committeemember	Gilleard, John
dc.contributor.committeemember	Lynch, Tarah
dc.contributor.committeemember	Niu, Dongyan
dc.date	2024-02
dc.date.accessioned	2023-12-06T17:03:22Z
dc.date.available	2023-12-06T17:03:22Z
dc.date.issued	2023-12-05
dc.description.abstract	Heligmosomoides bakeri, a parasitic nematode (roundworm) of mice, is closely related to economically important parasites of livestock and the hookworm parasites of humans. As a murine parasite it is more amenable to being maintained and manipulated in a controlled laboratory environment than its relatives. The worm enters its host during its third larval stage and develops through another larval stage into adults that reside in the lumen of the small intestine to mate and lay their eggs. Unravelling these processes and other processes critical to H. bakeri survival could reveal new targets to use for drug discovery for controlling this group of parasites as well as refine previous predictions of immunomodulatory molecules, which have therapeutic potential. My thesis aims to describe the gene expression of H. bakeri during the parasitic phase of its lifecycle. I first used RNA sequencing to investigate how the (whole worm) expression of genes varies across the parasite’s infection. Using differential gene expression analyses I identified genes important for development and genes important for the males vs the females. I also uncovered evidence of an increased importance for anaerobic respiration in the adults compared to the larvae and hypothesize that aerobic conditions are important for the critical developmental processes of molting and cuticle synthesis. I then analyzed single-cell RNA-seq data from young adult male and female worms. Leveraging cell type markers from the model nematode C. elegans allowed me to putatively identify gamete, embryo, intestine, hypodermis, neuron, and muscle cells. The resulting cluster expression profiles can guide investigations into tissue-specific aspects of the adult worms. Putative intestinal transcription profiles suggest compartmentalization of function along the anterior-posterior axis of the worms, with an emphasis on protein synthesis in the anterior portion, as has been observed in other worms. Embryonic profiles are noticeably different from C. elegans embryogenesis, particularly with respect to paternal contributions to the early embryo. Overall, these datasets extend our understanding of how H. bakeri lives as a parasite and provide a public resource for further investigation into genes of interest. They also lay the groundwork for more comprehensive comparisons among the phylum Nematoda.
dc.identifier.citation	Pollo, S. M. J. (2023). Biological insights into the parasitic nematode Heligmosomoides bakeri from bulk and single-cell transcriptomics (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.
dc.identifier.uri	https://hdl.handle.net/1880/117625
dc.identifier.uri	https://doi.org/10.11575/PRISM/42468
dc.language.iso	en
dc.publisher.faculty	Graduate Studies
dc.publisher.institution	University of Calgary
dc.rights	University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subject.classification	Bioinformatics
dc.subject.classification	Parasitology
dc.title	Biological insights into the parasitic nematode Heligmosomoides bakeri from bulk and single-cell transcriptomics
dc.type	doctoral thesis
thesis.degree.discipline	Veterinary Medical Sciences
thesis.degree.grantor	University of Calgary
thesis.degree.name	Doctor of Philosophy (PhD)
ucalgary.thesis.accesssetbystudent	I do not require a thesis withhold – my thesis will have open access and can be viewed and downloaded publicly as soon as possible.