Biology subjects

Horejsi, R. V.

Publications and source records attributed to Horejsi, R. V..

3 recordsLinked to original sources

bioRxiv2025

Tissue-specific distribution of eggs in the definitive host drives transcriptomic and behavioral differences in Schistosoma mansoni miracidia

Schistosomiasis is a neglected tropical disease caused by human-infective schistosomes (Trematoda: Schistosoma). Intestinal schistosomiasis in sub-Saharan Africa and the Neotropics is caused primarily by Schistosoma mansoni and is transmitted by several Biomphalaria planorbid snail species. Adult male and female parasites in the definitive mammalian host pair and reside in the mesenteric vasculature; females lay eggs that traverse the intestinal wall to be excreted, but a significant proportion become trapped in host tissues, especially the liver, eliciting granulomatous immune responses that underlie most disease pathology. S. mansoni is the primary lab model for research and, due to the abundance and ease of harvesting, liver-derived eggs are almost exclusively used to maintain the life cycle and to study miracidia and subsequent larval stages. However, recent evidence shows that eggs from the liver or intestine have key morphometric, transcriptomic, and antigenic differences, which can profoundly affect experimental outcomes. To determine whether these differences extend to the miracidia stage, we compared miracidia hatched from mouse liver and intestine-derived eggs, sequencing their transcriptomes and assessing their unstimulated behaviors over time in an arena allowing for high-resolution tracking of miracidia behavior at a large spatiotemporal scale. We found that while transcriptomic profiles of miracidia are distinguishable based on egg tissue origin, only a small subset of genes is differentially expressed. Further, basic, unstimulated behavior of miracidia that developed in different niches of the definitive host was significantly different. These different behavioral programs may reflect intrinsic developmental programming or differential viability and hardiness related to tissue origin. These findings underscore the importance of egg source in experimental design and interpretation, with significant implications for the maintenance of laboratory life cycles and the use of miracidia in schistosomiasis research.

molecular biology↗

bioRxiv2025

Quantitative ethology of schistosome miracidia characterizes a conserved snail peptide that inhibits penetration

Over 700 million people are at risk of contracting schistosomiasis due to regular exposure to freshwater sources where infected snails, the obligate intermediate hosts of schistosomes, are endemic. Although mass drug administration of praziquantel effectively controls the disease in most regions, achieving elimination will require reducing populations of infected snails that shed the human-infective larval stage. Considerable effort has focused on parasite development and immunological responses after snail penetration, but comparatively little is known about the molecular and behavioral host seeking events that precede it, primarily due to technical and physical constraints. To address this gap, we developed a custom imaging and computational system for tracking and screening schistosome miracidia, the snail-infective larval form that hatches from eggs. Our system employs an array of cameras without magnification and acrylic devices that maintain miracidia within the focal plane, create a field of view over 200,000 times the area of a single miracidium, and support the formation of stable chemical gradients. Using this platform, we perform quantitative ethology of miracidia at an unprecedented scale and extract features that drive the emergent chemoklinokinetic behavior in response to snail cues. We demonstrate that miracidia accumulate at the edge of a gradient of snail cues by increasing key chemoklinokinetic features upon leaving the region of a cue, corroborating previous reports. In contrast, miracidia do not exhibit these behaviors when the cue is uniform, demonstrating that they represent a specific sensory response rather than generic neuromuscular activity. We further find that a previously identified stimulatory snail peptide only partially recapitulates the full chemoklinokinetic profile, and homologues from closely related species elicit divergent behavioral outcomes. Notably, some of these snail peptides can mask a natural gradient and inhibit miracidia penetration of snails. This work establishes a scalable behavioral platform for probing parasite- snail interactions and identifies a peptide scaffold that potently blocks snail penetration.

animal behavior and cognition↗

bioRxiv2025

A graphical user interface for wrmXpress 2.0 streamlines helminth phenotypic screening

Image-based phenotypic screening is a fundamental technique used to better understand the basic biology of helminths and advance discovery of new anthelmintics. Miniaturization of screening platforms and automated microscopy have led to a surge in imaging data and necessitated software to organize and analyze these data. Traditionally, these analyses are performed remotely on high-performance computers, often requiring an understanding of a command-line interface (CLI) and the ability to write scripts to control the software or job scheduler. Requiring access to specialized computing equipment and advanced computational skills raises the barrier to entry for these sorts of studies. The development of efficient, performant computer and graphical processing units for personal computers and cheaper imaging solutions has made the requirement of remote servers superfluous for many small to medium-scale screens, but most analytical software still require interaction with a CLI. To democratize the analysis of image-based phenotypic screens, we have developed a graphical user interface (GUI) for wrmXpress, a tool that integrates many popular computational pipelines for analyzing imaging data of parasitic and free-living worms. The GUI operates on any personal computer using the operating systems native web browser, allowing users to configure and run analyses using a point-and-click approach. Containerization of the application eliminates the need to install specialized programming libraries and dependencies, further increasing the ease of use. GUI development required a substantial reorganization of the wrmXpress backend codebase, which allowed for the addition a new pipeline for high-resolution tracking of worm behavior, and we demonstrate its functionality by showing that praziquantel modulates the behavior of Schistosoma mansoni miracidia. These advances make cutting-edge analyses of image-based phenotyping of worms more equitable and accessible.

bioinformatics↗