# Oxygen sensation in human-parasitic skin-penetrating nematodes

> **NIH NIH F30** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $42,516

## Abstract

PROJECT SUMMARY / ABSTRACT
 The goal of this proposal is to leverage molecular neuroscience techniques to define the role of oxygen (O2)
as a biologically relevant chemosensory cue in the human-infective threadworm Strongyloides stercoralis.
Globally, S. stercoralis infects ~610 million people, with a high disease burden in resource-poor settings.
Strongyloidiasis, considered an emerging and/or re-emerging disease, can manifest as an indolent multi-decade
gastrointestinal infection; immunocompromised individuals are at high risk of hyperinfection syndrome and
disseminated disease – of which most cases are fatal. Given the threat of anthelmintic resistance, novel
chemotherapeutic strategies are needed to treat and cure individuals with strongyloidiasis.
 Parasitic nematodes rely upon neuronally detected sensory cues to actively seek hosts, navigate intra- and
extra-host environments, and coordinate their development with their local context. S. stercoralis, as a soil-
transmitted helminth, thrives in O2 concentrations that range from atmospheric levels (~21%) at the soil surface
to near-anaerobic conditions in the host intestinal tract. However, O2 sensation remains completely unstudied in
S. stercoralis or any other parasitic nematode. This proposal hypothesizes that the neural and molecular
machinery mediating O2 sensation in S. stercoralis may yield promising targets vulnerable to intervention.
 This proposal will explore O2 sensation in S. stercoralis at the behavioral, neuronal, and molecular levels. The
first aim of this proposal seeks to characterize how O2 serves as a chemosensory cue to sculpt the motile
behaviors of S. stercoralis throughout its parasitic life cycle. Quantitative analysis of parasite behaviors in
different O2 contexts will be performed. Additionally, work proposed in the first aim will interrogate the role of
shifting O2 levels as a developmental cue that enables parasitism. In the second aim of this proposal,
chemogenetic neuronal silencing and calcium imaging techniques will be employed to both identify O2-sensing
neurons and describe parasite-specific encoding properties in these neurons. In the proposal’s third aim,
CRISPR/Cas9-mediated mutagenesis and ectopic expression systems will be used to determine the molecular
sensors of O2 in S. stercoralis and explore their mechanism of action. This proposal will generate new insights
into parasite chemosensory neurobiology and may reveal novel strategies for preventing nematode infections.
 This proposal will support the applicant’s goal of becoming a physician-scientist dedicated to the study and
clinical management of parasitic infectious diseases. In completing the proposed aims, the applicant will augment
prior training in parasitology and molecular biology with the development of new skills in neuroscience research.
This work will be performed in one of the only laboratories studying neurobiology in parasitic nematodes; the
applicant will also seek mentorship from the...

## Key facts

- **NIH application ID:** 10750771
- **Project number:** 1F30AI179222-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Breanna M. Walsh
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $42,516
- **Award type:** 1
- **Project period:** 2023-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10750771

## Citation

> US National Institutes of Health, RePORTER application 10750771, Oxygen sensation in human-parasitic skin-penetrating nematodes (1F30AI179222-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10750771. Licensed CC0.

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