Thursday, November 21, 2024 11/21/2024

Development of a multiplexed assay in kinetoplastid parasites to identify probes for glycolysis

Award Number: R01AI156382
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary/Abstract Parasite infection with members of the class Kinetoplastea, including Trypanosoma brucei and Leishmania spp., places a tremendous burden on human health, with an estimated ~1.4 million cases of disease recorded in 2015 (World Health Organization). Despite the widespread impact of these organisms, there remain major gaps in our understanding of fundamental parasite biology. For example, it is appreciated that glucose is a critical metabolite that can also serve to regulate important developmental pathways in the parasites. However, our understanding of these areas, particularly in the context of living parasites, is extremely limited. We propose to elucidate key mechanistic aspects of kinetoplastid glucose metabolism in kinetoplastids using a validated, yet unprecedented, screening assay platform based on live parasites expressing protein sensors that measure glucose uptake, distribution, and metabolism. We will adopt these cells to a novel and effective multiplexed high-throughput screening assay to identify small molecule probes that disrupt glucose uptake, distribution and metabolism in live parasites. This unique approach will simultaneously identify inhibitors of glycolysis that possess chemical properties required for delivery to the cellular target. Hits from the screening of a structurally diverse 100,000 compound collection will be validated by resynthesis, reconfirmation and counter- screening. Target identification, which will be facilitated by mapping the impact of the inhibitor on the pathway using the read-out from the assay, will be confirmed using reverse genetic and proteomic approaches. Last, the identified small molecule glycolytic probe inhibitors will be improved by SAR and their activity against parasites scored. Expected outcomes include development of a screening strategy that will be applicable to many types of cells, along with the identification of validated probes that dissect an essential parasite metabolic pathway.


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: 2024 ( Subtotal = $584,976 )
2024	2024	CLEMSON UNIVERSITY	201 SIKES HALL	CLEMSON	SC	29634	PICKENS	USA	Allergy and Infectious Diseases Research	001	4	2/21/2024	SUPPLEMENT FOR EXPANSION	$66,149
2024	2024	CLEMSON UNIVERSITY	201 SIKES HALL	CLEMSON	SC	29634	PICKENS	USA	Allergy and Infectious Diseases Research	002	4	5/23/2024	NON-COMPETING CONTINUATION	$51,883
2024	2024	CLEMSON UNIVERSITY	201 SIKES HALL	CLEMSON	SC	29634	PICKENS	USA	Allergy and Infectious Diseases Research	003	4	9/5/2024	NON-COMPETING CONTINUATION	$0
2024	2024	CLEMSON UNIVERSITY	201 SIKES HALL	CLEMSON	SC	29634	PICKENS	USA	Allergy and Infectious Diseases Research	000	4	2/16/2024	NON-COMPETING CONTINUATION	$466,944
														Subtotal = $584,976

Issue Date FY: 2023 ( Subtotal = $609,552 )
2023	2023	CLEMSON UNIVERSITY	201 SIKES HALL	CLEMSON	SC	29634	PICKENS	USA	Allergy and Infectious Diseases Research	001	3	3/20/2023	NON-COMPETING CONTINUATION	$524,577
2023	2023	CLEMSON UNIVERSITY	201 SIKES HALL	CLEMSON	SC	29634	PICKENS	USA	Allergy and Infectious Diseases Research	002	3	3/23/2023	SUPPLEMENT FOR EXPANSION	$66,149
2023	2023	CLEMSON UNIVERSITY	201 SIKES HALL	CLEMSON	SC	29634	PICKENS	USA	Allergy and Infectious Diseases Research	000	2	1/26/2023	SUPPLEMENT FOR EXPANSION	$18,826
														Subtotal = $609,552

Issue Date FY: 2022 ( Subtotal = $497,486 )
2022	2022	CLEMSON UNIVERSITY	201 SIKES HALL	CLEMSON	SC	29634	PICKENS	USA	Allergy and Infectious Diseases Research	000	2	3/11/2022	NON-COMPETING CONTINUATION	$497,486
														Subtotal = $497,486

Issue Date FY: 2021 ( Subtotal = $223,077 )
2021	2021	CLEMSON UNIVERSITY	201 SIKES HALL	CLEMSON	SC	29634	PICKENS	USA	Allergy and Infectious Diseases Research	000	1	4/2/2021	NEW	$223,077
														Subtotal = $223,077

Grand Total All Awards = $1,915,091

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Development of a multiplexed assay in kinetoplastid parasites to identify probes for glycolysis

Award Number: R01AI156382

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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