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Nematicidal Chalcones: A Genetic Approach to Uncovering the Action Mechanism

Award Number: R16GM145429
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/15/2022
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Nematicidal Chalcones: A Genetic Approach to Uncovering the Action Mechanism - Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text. Nematicidal chalcones: a genetic approach to uncovering the action mechanism Project Summary/Abstract: Parasitic Nematodes (PNs) are enemy to both plant and animals (including humans). These parasites have a tremendous impact on medicine, veterinary medicine, and agriculture, causing human infections and mortality (http://www.who.int/mediacentre/factsheets/fs366/en/) and significant annual monetary losses. For example, only in agriculture there is an estimated loss of $157 billion worldwide (Li et al., 2007) due to infestation by plant parasitic nematodes. Therefore, developing new nematicidal agents and understanding their mechanism of action is of paramount importance; it is likely that a solution to nematode control will come from the use of cocktails of nematicidal agents, which can control nematodes in different ways. Previous work in our lab identified two organic chalcones (chalcones 17 and 30) as effective nematicidals on Caenorhabditis elegans and the plant parasitic nematode Meloidogyne incognita (Saeed, et al. 2012, and Calderón-Urrea, et al., unpublished results). Furthermore, these chalcones have no significant effects on either soil microorganisms or human cells (Calderón-Urrea, et al., unpublished results). However, the mechanism of action of these chalcones is not known. It is possible that these chalcones target essential proteins (enzymes), which are rendered ineffective by the chalcones. If this is the case, alterations in the binding of the chalcones to said proteins can be a powerful tool to elucidate the mechanism of action of the chalcones. We hypothesize that “the susceptibility to chalcones is due to the action of the chalcone on a protein product, perhaps an enzyme, and therefore mutations on the gene (or genes) encoding that protein will render the chalcone action ineffective”. We are testing this hypothesis by conducting a forward genetic screen on mutagenized C. elegans nematodes, and characterizing the isolated mutants. The specific objectives of this project are: 1) To test resistance to chalcones 17 and 30 and identification of mutants overcoming chalcone effects; 2) Characterization of chalcone resistant mutants; and 3) Identification of the DNA sequences involved in the chalcone resistant mutants. The PI will use his extensive experience in recruiting and training students [graduate (MS level) and undergraduate], to actively engage them in the execution of this project.


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: 2025 ( Subtotal = $136,000 )
2025	2025	CALIFORNIA STATE UNIVERSITY, FRESNO	5150 N MAPLE AVE	FRESNO	CA	93740	FRESNO	USA	Biomedical Research and Research Training	000	4	6/12/2025	NON-COMPETING CONTINUATION	$136,000
														Subtotal = $136,000

Issue Date FY: 2024 ( Subtotal = $216,000 )
2024	2024	CALIFORNIA STATE UNIVERSITY, FRESNO	5150 N MAPLE AVE	FRESNO	CA	93740	FRESNO	USA	Biomedical Research and Research Training	001	3	7/18/2024	SUPPLEMENT FOR EXPANSION	$80,000
2024	2024	CALIFORNIA STATE UNIVERSITY, FRESNO	5150 N MAPLE AVE	FRESNO	CA	93740	FRESNO	USA	Biomedical Research and Research Training	000	3	5/17/2024	NON-COMPETING CONTINUATION	$136,000
														Subtotal = $216,000

Issue Date FY: 2023 ( Subtotal = $199,010 )
2023	2023	CALIFORNIA STATE UNIVERSITY, FRESNO	5150 N MAPLE AVE	FRESNO	CA	93740	FRESNO	USA	Biomedical Research and Research Training	001	2	8/10/2023	SUPPLEMENT FOR EXPANSION	$65,010
2023	2023	CALIFORNIA STATE UNIVERSITY, FRESNO	5150 N MAPLE AVE	FRESNO	CA	93740	FRESNO	USA	Biomedical Research and Research Training	000	2	3/16/2023	NON-COMPETING CONTINUATION	$134,000
														Subtotal = $199,010

Issue Date FY: 2022 ( Subtotal = $113,759 )
2022	2022	CALIFORNIA STATE UNIVERSITY, FRESNO	5241 N MAPLE AVE	FRESNO	CA	93740	FRESNO	USA	Biomedical Research and Research Training	000	1	4/11/2022	NEW	$113,759
														Subtotal = $113,759

Grand Total All Awards = $664,769

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Nematicidal Chalcones: A Genetic Approach to Uncovering the Action Mechanism

Award Number: R16GM145429

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/15/2022

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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