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Engineered probiotic bacteria for toxin elimination

Award Number: R21ES038018
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: 07/01/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2028

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Engineered probiotic bacteria for toxin elimination - SUMMARY/ABSTRACT Lead (Pb) poisoning remains a global health problem, causing neurodevelopmental anomalies in children and increased risk of cardiovascular, renal, and neurological disease in adults. Pb cumulatively deposits into bones and can take years to be eliminated from the body. Pb neurotoxic effects are permanent. Therapeutic elimination of Pb is not feasible for most affected people. The standard of treatment for Pb toxicity is chelation therapy with oral medication, or intravenous EDTA administration. However, these therapies are only offered in cases of extremely high Pb levels even when ten times lower levels are linked to pathologies. Importantly, Pb poisoning disproportionately affects low-income communities. Thus, there is an urgent need for cost-effective methods to protect individuals from cumulative Pb exposure. Aptamers are short stretches of nucleic acids (<100 nucleotide single-stranded DNA or RNA molecules) that bind specifically a target molecule or ion. We have shown specific interactions of aptamers with Pb ions. Using the nematode C. elegans as a model of Pb toxicity, we have shown that Pb-binding aptamers applied to worms or mixed with their food (E. coli OP50) completely protected the animals from neurotoxic and reproductive phenotypes caused by Pb exposure. These remarkable results suggest that Pb-binding aptamers could be used to bind Pb in the gastrointestinal tract and thereby prevent intestinal absorption of Pb. As gastrointestinal absorption is a critical route of Pb exposure, we hypothesize that probiotic bacteria expressing RNA aptamers could absorb Pb in the gastrointestinal tract, thereby reducing human Pb absorption from ingested sources. The objective of this proposal is to design a probiotic bacteria strain expressing Pb aptamers as a prophylactic for Pb toxicity. We propose to: Aim 1: Build and test engineered bacterial probiotics to protect C. elegans from Pb toxicity. We will determine whether expression of aptamers within transgenic probiotic bacteria (E. coli Nissle, EcN) lead to Pb accumulation and thereby protection of C. elegans from Pb-induced reproductive and neurotoxic phenotypes. Aim 2: Computationally identify endogenous E. coli Nissle sequences capable of binding Pb. Engineered probiotics are subject to regulatory approval by the federal government. The integration of synthetic DNA into bacteria faces greater scrutiny, but rearrangement of DNA sequences that already exist within the target bacteria genome faces fewer regulatory hurdles. We propose to develop a novel reinforcement learning algorithm that selects sequences with high likelihood of Pb binding from within the EcN genome. Developing aptamer-based approaches to prevent gastrointestinal absorption of Pb will represent a significant improvement over reactive treatments such as chelation therapy. Moreover, our AI-driven method of host genome computational mining for novel aptamer sequences will represent a breakthrough in the design of biological metal chelators and engineered probiotic strains for human health.


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 = $400,753 )
2026	2026	WORCESTER POLYTECHNIC INSTITUTE	100 INSTITUTE RD	WORCESTER	MA	01609	WORCESTER	USA	Environmental Health	000	1	6/23/2026	NEW	$400,753
														Subtotal = $400,753

Grand Total All Awards = $400,753

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Engineered probiotic bacteria for toxin elimination

Award Number: R21ES038018

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: 07/01/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2028

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