# Mechanosensory Behaviors of Skin-Penetrating Parasitic Nematodes

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $69,500

## Abstract

PROJECT SUMMARY/ABSTRACT
The overall goal of this research proposal is to characterize the mechanosensory behaviors of skin-penetrating
parasitic nematodes that enable the location and invasion of a host organism. Skin-penetrating parasitic
nematodes, including the threadworm Strongyloides stercoralis, infect nearly one billion people worldwide and
are major sources of neglected tropical disease. S. stercoralis is normally found in the soil as infective third-
stage larvae (iL3s); soil-dwelling iL3s engage in a variety of behaviors that are thought to increase the likelihood
of host contact. The hypothesis that the sensation of mechanical stimuli by S. stercoralis iL3s and the ensuing
behavioral response are together integral to host seeking and skin penetration has long been postulated but has
not been tested. Furthermore, the underlying mechanotransduction pathways and mechanosensory neuronal
circuits are not known. The experiments in this proposal will address this gap in knowledge. The first set of
experiments will characterize the behavioral response of S. stercoralis iL3s to vibrations resembling those
generated by humans walking on soil. Specifically, the extent to which vibration attracts iL3s and promotes
behaviors that facilitate host attachment, including nictation, will be examined in detail. In parallel, an in-depth
analysis of the behavioral paradigm of skin penetration will be conducted using human skin. The proposed
experiments will also determine whether the stiffness or texture that is particular to human skin promotes skin
penetration. Behaviors induced by exposure to vibration and host skin will also be studied in other species of
parasitic nematodes – the skin-penetrating human-parasitic hookworm Ancylostoma ceylanicum and the
passively ingested murine parasite Heligmosomoides polygyrus – and the free-living nematode Caenorhabditis
elegans to identify species-specific behavioral adaptations of skin-penetrating nematodes. Additionally, this work
will identify the mechanosensory genes and circuits that underlie host seeking and skin penetration by using a
combination of approaches: transcriptional reporters for genes that encode predicted mechanoreceptors to
identify putative mechanosensory neurons; targeted mutagenesis of the same genes with CRISPR/Cas9
followed by tracking of behavior; chemogenetic silencing of potential mechanosensory neurons using the
histamine-gated chloride channel HisCl1 followed by behavioral studies; and imaging of calcium transients in the
same neurons upon stimulation. Together, the work in this proposal will identify the mechanosensory behaviors
that are specific to skin-penetrating parasitic nematodes that enable host contact and host invasion. Existing
therapeutics for strongyloidiasis do not prevent re-infection; this work may alleviate the problem by uncovering
novel molecular targets for the development of preventive anthelmintic drugs and topical creams.

## Key facts

- **NIH application ID:** 10606463
- **Project number:** 1F32AI174816-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Ruhi Patel
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $69,500
- **Award type:** 1
- **Project period:** 2022-12-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10606463

## Citation

> US National Institutes of Health, RePORTER application 10606463, Mechanosensory Behaviors of Skin-Penetrating Parasitic Nematodes (1F32AI174816-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10606463. Licensed CC0.

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