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Advancing Spatial Metallomics/Metabolomics, Genome Editing, and Biocatalysis by Designing and Selecting DNAzymes, Aptamers, and Biosynthetic Models

Award Number: R35GM141931
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: 06/01/2021
PERIOD OF PERFORMANCE END DATE: 01/31/2031

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Advancing Spatial Metallomics/Metabolomics, Genome Editing, and Biocatalysis by Designing and Selecting DNAzymes, Aptamers, and Biosynthetic Models - Project summary/Abstract The overall goal is to develop novel tools to advance spatial metallomics, spatial metabolomics, genome editing, and biocatalysis by designing and selecting DNAzymes, DNA aptamers, and biosynthetic models of heteronuclear metalloenzymes involved in multi-electron and multi-proton processes. In the first project, we plan to develop super-resolution imaging methods to map metal ions and metabolites at nanometer resolution in vitro and in vivo based on DNAzymes and aptamers that are highly selective for metal ions and metabolites. To achieve three-dimensional ratiometric mapping of metal ions and metabolites in living cells and mouse tissues, we will develop specific nucleic acid intramolecular ligation (SNAIL) probes for DNAzymes and aptamers. Additionally, we will introduce electrophilic sulfonyl fluoride-modified DNAzymes and aptamers to understand metal ion/metabolite interactions with proteins. These advancements will address critical challenges in spatial metallomics and metabolomics, bringing our understanding of metal ion and metabolite distributions to the same level as spatial transcriptomics.. In the second project, we seek to establish an alternative genome editing strategy to CRISPR/Cas by integrating peptide nucleic acids for targeted double-stranded DNA opening and DNAzymes engineered for precise DNA cleavage under physiological conditions. This approach promises to overcome current CRISPR/Cas limitations, offering greater sequence fidelity, expanded gene accessibility in compacted genome regions, and reduced immunogenicity. Finally, we will design biosynthetic models of nitric oxide reductases (NORs), heme-copper oxidases (HCOs), and heme-copper sulfite reductases (SiRA) using small, stable protein scaffolds. By refining existing models, identifying alternative scaffolds from the Protein Data Bank, and employing generative protein design methods, we aim to gain a holistic understanding of the structural features that enable efficient and selective 2-, 4-, and 6- electron catalytic reduction of NO, O2, and SO32-, respectively.


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 = $682,295 )
2026	2026	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Biomedical Research and Research Training	000	7	6/3/2026	COMPETING CONTINUATION	$682,295
														Subtotal = $682,295

Issue Date FY: 2025 ( Subtotal = $580,456 )
2025	2025	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Biomedical Research and Research Training	001	6	7/21/2025	NON-COMPETING CONTINUATION	$580,456
2025	2024	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Biomedical Research and Research Training	000	5	11/6/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $580,456

Issue Date FY: 2024 ( Subtotal = $680,643 )
2024	2024	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Biomedical Research and Research Training	001	5	8/27/2024	SUPPLEMENT FOR EXPANSION	$99,915
2024	2024	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Biomedical Research and Research Training	000	5	7/3/2024	NON-COMPETING CONTINUATION	$580,728
														Subtotal = $680,643

Issue Date FY: 2023 ( Subtotal = $580,996 )
2023	2023	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Biomedical Research and Research Training	002	4	6/9/2023	NON-COMPETING CONTINUATION	$580,996
2023	2021	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	000	1	10/23/2022	NEW	-$1
2023	2021	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Biomedical Research and Research Training	001	2	10/23/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1
														Subtotal = $580,996

Issue Date FY: 2022 ( Subtotal = $553,744 )
2022	2022	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Biomedical Research and Research Training	002	3	7/28/2022	NON-COMPETING CONTINUATION	$581,259
2022	2021	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Biomedical Research and Research Training	001	2	4/19/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$344,601
2022	2021	UNIVERSITY OF ILLINOIS	352 HENRY ADMINISTRATION BLDG	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	000	1	4/18/2022	NEW	-$372,116
														Subtotal = $553,744

Issue Date FY: 2021 ( Subtotal = $372,117 )
2021	2021	UNIVERSITY OF ILLINOIS	364 HENRY ADMINISTRATION BLDG	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	000	1	6/1/2021	NEW	$372,117
														Subtotal = $372,117

Grand Total All Awards = $3,450,251

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Advancing Spatial Metallomics/Metabolomics, Genome Editing, and Biocatalysis by Designing and Selecting DNAzymes, Aptamers, and Biosynthetic Models

Award Number: R35GM141931

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: 06/01/2021

PERIOD OF PERFORMANCE END DATE: 01/31/2031

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