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Juvenile hormone transporters in disease vector physiology

Award Number: R01AI171032
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/24/2023
PERIOD OF PERFORMANCE END DATE: 12/31/2027

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Juvenile hormone transporters in disease vector physiology - PROJECT SUMMARY/ABSTRACT Development and reproduction of insects, including human disease vectors such as mosquitoes, are mainly controlled by two lipophilic hormones: ecdysone and juvenile hormone (JH). Although these hormones need to enter their target cells to exert their biological effects, almost nothing is known regarding molecular mechanisms that regulate hormone transport across cellular membranes. This is due to the prevailing dogma in endocrinology that lipophilic hormones enter and exit cells by simple diffusion across lipid bilayers. However, despite this dominant assumption, the simple diffusion model of lipophilic hormone transport is not supported by any conclusive evidence in any organism. Indeed, recent studies now suggest that some lipophilic hormones, including the insect steroid hormone ecdysone, require membrane transporter proteins to travel across plasma membranes. The overall objective of this project is to identify and characterize membrane transporters required for JH trafficking across cellular membranes, and to thereby challenge the conventional paradigm that lipophilic hormones freely enter and exit cells by simple diffusion. The approach will combine in vitro and in vivo approaches to characterize JH Transporter (JHT), which was discovered in preliminary studies using the fruit fly model system. In Aim 1, functions of the JHT ortholog in the yellow fever mosquito Aedes aegypti, the primary vector for Zika, yellow fever, chikungunya, and dengue viruses, will be thoroughly investigated in vitro using an arsenal of molecular genetic tools. In Aim 2, JHT functions will be further studied genetically in Aedes. As JH controls both growth and reproduction in Aedes and other mosquitoes, characterization of Aedes JHT is expected to aid our effort to combat these deadliest disease vectors for humans. Indeed, in Aim 3, in vitro chemical screening will be conducted to identify compounds that can inhibit functions of Aedes JHT, and their effects will be tested in vivo. The significance of this project is therefore not just to overturn the long-standing dogma in endocrinology, but also to provide a critical proof of concept as well as seed compounds for developing novel pharmacological tools to control mosquitoes and other deadly disease vector insects.


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 = $378,686 )
2026	2026	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Allergy and Infectious Diseases Research	000	4	12/19/2025	NON-COMPETING CONTINUATION	$378,686
														Subtotal = $378,686

Issue Date FY: 2025 ( Subtotal = $367,695 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Allergy and Infectious Diseases Research	000	3	12/11/2024	NON-COMPETING CONTINUATION	$367,695
														Subtotal = $367,695

Issue Date FY: 2024 ( Subtotal = $379,432 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Allergy and Infectious Diseases Research	000	2	11/29/2023	NON-COMPETING CONTINUATION	$341,489
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Allergy and Infectious Diseases Research	001	2	5/21/2024	NON-COMPETING CONTINUATION	$37,943
														Subtotal = $379,432

Issue Date FY: 2023 ( Subtotal = $379,641 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Allergy and Infectious Diseases Research	000	1	1/24/2023	NEW	$379,641
														Subtotal = $379,641

Grand Total All Awards = $1,505,454

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Juvenile hormone transporters in disease vector physiology

Award Number: R01AI171032

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/24/2023

PERIOD OF PERFORMANCE END DATE: 12/31/2027

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