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Neural mechanisms of gas sensing in a human-infective worm

Award Number: R01DC021489
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2028

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Neural mechanisms of gas sensing in a human-infective worm - PROJECT SUMMARY Skin-penetrating nematodes, including the human-parasitic threadworm Strongyloides stercoralis, infect over one billion people worldwide and are a major source of morbidity in low-resource settings. Infections can cause gastrointestinal distress, stunted growth and cognitive impairment in children, and even death in the case of S. stercoralis infection. S. stercoralis infective larvae are developmentally arrested third-stage larvae that navigate through the soil searching for hosts to infect. When they find a host, they infect by skin penetration, resume growth and development inside the host in a process called activation, and navigate through the host body to the small intestine. These parasites encounter widely varying levels of ambient oxygen (O2) and carbon dioxide (CO2) throughout their life cycle, ranging from the near-atmospheric levels of O2 and CO2 they encounter as infective larvae host seeking at the soil surface to the low O2/high CO2 levels they encounter as parasitic adults residing in the human intestine. However, remarkably little is known about gas sensing in S. stercoralis or any other mammalian-parasitic nematode. We propose to investigate the behavioral, neural, and molecular mechanisms of gas sensing in S. stercoralis. We will conduct an in-depth, quantitative analysis of the behavioral responses of S. stercoralis to acute changes in ambient O2 and CO2 levels as well as O2, CO2, and combined O2/CO2 gradients using automated worm motility tracking. We will compare the responses of infective larvae, activated infective larvae, free-living adults, and parasitic adults to changes in ambient O2 and CO2 to determine how O2/CO2-evoked behaviors vary across life stages. We will then map and functionally characterize the neural microcircuits that mediate behavioral responses to changes in ambient O2 and CO2. We will test the hypothesis that the S. stercoralis homologs of sensory neurons and interneurons that mediate gas sensing in C. elegans also mediate gas sensing in S. stercoralis but contain functional adaptations that enable parasite-specific behavioral responses. Finally, we will identify and characterize the O2 and CO2 receptors that are required for gas sensing in S. stercoralis. Together, our results will provide insight into how skin-penetrating nematodes use gas sensing to find and infect human hosts. In the long-term, our results may identify new molecular targets that could inform the design of novel anthelmintic drugs.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $545,955 )
2026	2026	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Research Related to Deafness and Communication Disorders	000	3	12/2/2025	NON-COMPETING CONTINUATION	$545,955
														Subtotal = $545,955

Issue Date FY: 2025 ( Subtotal = $607,527 )
2025	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Research Related to Deafness and Communication Disorders	000	2	11/20/2024	NON-COMPETING CONTINUATION	$546,775
2025	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Research Related to Deafness and Communication Disorders	001	2	4/21/2025	NON-COMPETING CONTINUATION	$60,752
														Subtotal = $607,527

Issue Date FY: 2024 ( Subtotal = $613,927 )
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Research Related to Deafness and Communication Disorders	001	1	10/26/2023	NEW	$4,487
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Research Related to Deafness and Communication Disorders	000	1	10/19/2023	NEW	$609,440
														Subtotal = $613,927

Grand Total All Awards = $1,767,409

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Neural mechanisms of gas sensing in a human-infective worm

Award Number: R01DC021489

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 12/01/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2028

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