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Halogenation Biochemistry in Human and Environmental Health

Award Number: R35GM142882
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: 07/01/2021
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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Halogenation Biochemistry in Human and Environmental Health - PROJECT SUMMARY Biotic processes in the oceans introduce various halogenated molecules in the environment and in the human exposome. Some of these halogenated molecules possess favorable pharmaceutical activities making them attractive drug candidates while many of these naturally produced marine halogenated molecules are potent toxins and pollutants. Understanding, at the organismal, molecular, and atomistic levels how these halogenated molecules are naturally constructed in the oceans is the principal motivation of the research program described herein. Seaweeds and filter feeding marine benthic invertebrates such as sponges are well validated to be exceptionally prolific producers of halogenated natural products. Contrary to prokaryotic natural product biochemistry, our understanding of how these eukaryotes biosynthesize natural products is far less developed due to challenges in culturing and genetically interrogating these organisms. This is the key scientific challenge that this proposal seeks to address in order to deliver seaweed- and sponge-derived halogenated natural products using biogenetic means. Progress envisaged here is predicated upon two key intellectual drivers. The first of these is the sequencing of eukaryotic transcriptomes, rather than genomes, to circumvent the eukaryotic genome complexity. The second driver is to design natural product biosynthetic schemes based on intermediates that are mined from untargeted metabolomic datasets and then use these rationalized schemes to guide the mining of eukaryotic transcriptomes for biosynthetic enzyme discovery. Specifically, halogenated intermediates and halogenating enzymes are used as diagnostic signatures in this workflow. Interdisciplinary competence in genomics, biochemistry, synthetic biology, and metabolomics allows the program participants to not only interrogate biogenetic pathways for the production of marine eukaryote- derived halogenated pharmacophores and pollutants, but to also use the genetic dark matter locked away in marine holobiont metagenomes to produce new-to-nature halogenated molecules with favorable pharmaceutical bioactivities. The program design also embraces opportunities to discover and characterize new halogenation enzymology and adapt halogenases as general purpose biocatalysts. Research described here is both molecule focused, in that, it will lead to the understanding of how key halogenated molecules of interest are constructed in marine sponge biomes, while concomitantly embracing method-development and engineering opportunities.


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 = $373,752 )
2025	2025	GEORGIA TECH RESEARCH CORP	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Biomedical Research and Research Training	000	5	4/10/2025	NON-COMPETING CONTINUATION	$373,752
														Subtotal = $373,752

Issue Date FY: 2024 ( Subtotal = $373,752 )
2024	2024	GEORGIA TECH RESEARCH CORP	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Biomedical Research and Research Training	000	4	5/9/2024	NON-COMPETING CONTINUATION	$373,752
														Subtotal = $373,752

Issue Date FY: 2023 ( Subtotal = $373,752 )
2023	2023	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Biomedical Research and Research Training	000	3	4/11/2023	NON-COMPETING CONTINUATION	$373,752
														Subtotal = $373,752

Issue Date FY: 2022 ( Subtotal = $373,752 )
2022	2022	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Biomedical Research and Research Training	000	2	6/29/2022	NON-COMPETING CONTINUATION	$373,752
														Subtotal = $373,752

Issue Date FY: 2021 ( Subtotal = $373,752 )
2021	2021	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Biomedical Research and Research Training	000	1	6/23/2021	NEW	$373,752
														Subtotal = $373,752

Grand Total All Awards = $1,868,760

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Halogenation Biochemistry in Human and Environmental Health

Award Number: R35GM142882

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: 07/01/2021

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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