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A novel technology to assess chronic toxicity in genetically diverse nematode populations

Award Number: R43ES032516
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/12/2021
PERIOD OF PERFORMANCE END DATE: 07/31/2022

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A novel technology to assess chronic toxicity in genetically diverse nematode populations - Project Abstract The number of new products such as drugs, cosmetics and food additives introduced into the market is growing and poses a significant challenge for risk prediction. Currently, vertebrate testing is the industry standard for hazard assessment but has limitations including high costs, and the growing public and corporate sentiment against using vertebrates for chemical testing. Importantly, current toxicity assessment does not incorporate genetic diversity leading to failure of drug candidates and unintended risks to human sub-populations. The celebrated invertebrate model C. elegans has the potential to fill this gap since thousands of genetically diverse nematode populations are available. However, the main challenge is that chronic studies of chemicals in the nematode model is still tedious, precluding large-scale toxicity testing in nematode populations. This proposal aims to develop a high-throughput technology for chronic toxicity screening of diverse genetic populations in adult C. elegans. The focus of our Phase I plan is to pursue chronic toxicity studies on select toxins and generate foundational data highlighting the impact of genetic diversity, and subsequently scale the NemaLife technology to enable large-scale genetic diversity screening. AIM 1: To generate chronic dose-response data on toxins affecting diverse C. elegans strains. We will test the effects of five toxins for which we know the variability in human and rodent responses. Animals will be exposed to toxins daily, followed by scoring of survival, reproductive and neuromuscular health. About 1200 whole-life assays will be conducted with data acquired on 500+ animals per assay condition. We will generate data that will define the rank-order of C. elegans toxin response vis-à-vis mammalian systems, optimize phenotyping conditions for large numbers of strains per species, and define the amount of heritable variation in toxin responses. These pilot data will validate the capabilities afforded by our screening platform. AIM 2: To scale the throughput of NemaLife Technology for thousands of chronic toxicity assays. Currently, NemaLife’s technology has a throughput of hundreds of chronic toxicity assays. However, given the large number of toxins and vast library of genetic strains and wild isolates available, there is a significant need to increase the throughput of our technology. Therefore, we will develop the technology infrastructure and workflow to scale the throughput which includes multiplexing our approach, scale-up of chip fabrication and streamlining data analysis. Technology development at the scale of thousands of whole-life toxicity assays in a few weeks with readouts on animal death and neuromuscular impairments will be a major breakthrough in the field opening up new business opportunities in toxicity testing in the drug and consumer industry.


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: 2023 ( Subtotal = $0 )
2023	2021	NEMALIFE INC	3911 4TH ST	LUBBOCK	TX	79409	LUBBOCK	USA	Environmental Health	001	1	5/16/2023	NEW	$0
2023	2021	NEMALIFE INC	3911 4TH ST	LUBBOCK	TX	79409	LUBBOCK	USA	Environmental Health	000	1	5/15/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	NEMALIFE INC.	3911 4TH ST	LUBBOCK	TX	79409	LUBBOCK	USA	Environmental Health	000	1	12/2/2021	NEW	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $251,040 )
2021	2021	NEMALIFE INC.	3911 4TH ST	LUBBOCK	TX	79409	LUBBOCK	USA	Environmental Health	000	1	2/11/2021	NEW	$251,040
														Subtotal = $251,040

Grand Total All Awards = $251,040

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A novel technology to assess chronic toxicity in genetically diverse nematode populations

Award Number: R43ES032516

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/12/2021

PERIOD OF PERFORMANCE END DATE: 07/31/2022

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