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Mechanisms and Applications of RNA-mediated Enzymes in Translation and Immunity

Award Number: R35GM152081
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: 02/12/2024
PERIOD OF PERFORMANCE END DATE: 01/31/2029

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Mechanisms and Applications of RNA-mediated Enzymes in Translation and Immunity - Description: RNA-guided, or ribonucleoprotein particle (RNP), enzymes comprise an emerging class of molecules that function in a wide range of biological pathways. Unlike most of the protein-based enzymes, RNP enzymes rely on the guide RNA to secure the substrates and on the partner proteins to catalyze the chemical reactions. The RNA-guided targeting mechanism has created unprecedented opportunities in genome manipulation, gene regulation and nucleic acid detection. Research in the Li laboratory employs structural biology and complementary methods to uncover the theoretical basis for their biological function and effective use as research, diagnostic and therapeutic tools. In the proposed funding period, the Li laboratory will tackle the mechanisms of the RNP enzymes to enable their applications. These include the methylation-sensitive Clustered, Regularly Interspaced, Short Palindromic Repeats (CRISPR)-Cas9, the multi-functional Type III CRISPR effectors and their associated signaling processes, and the small nucleolar RNPs (snoRNPs) responsible for chemical modifications of ribosomal RNA. Though unrelated in enzyme composition or biological pathway, these RNP enzymes are governed by a similar set of physicochemical principles and share the great potential in therapeutic and diagnostic innovations by reprogramming the chemistry of cellular nucleic acids. The proposed research will assess the feasibility of engineering and applying the epigenetic DNA-specific Cas9, the utility of rapid virus detection with the CRISPR Type III effectors, and the possibility of tunning cellular functions through chemical modifications of RNA. The Li laboratory has assembled a team of scientists with complementary expertise in microbiology, mammalian genome biology, yeast genetics, single molecule biophysics, virology, virus detection, X-ray crystallography, and high-throughput cryogenic electron microscopy to maximize the impact while mitigating the risks of the research. The goal of this transformative proposal is to demonstrate and enable the applicability of the RNA-mediated enzymes in a wide range of biomedical fields.


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 = $563,163 )
2026	2026	VAN ANDEL RESEARCH INSTITUTE	333 BOSTWICK AVE NE	GRAND RAPIDS	MI	49503	KENT	USA	Biomedical Research and Research Training	000	4	1/30/2026	NON-COMPETING CONTINUATION	$563,163
														Subtotal = $563,163

Issue Date FY: 2025 ( Subtotal = $625,736 )
2025	2025	VAN ANDEL RESEARCH INSTITUTE	333 BOSTWICK AVE NE	GRAND RAPIDS	MI	49503	KENT	USA	Biomedical Research and Research Training	000	3	1/17/2025	NON-COMPETING CONTINUATION	$563,163
2025	2025	VAN ANDEL RESEARCH INSTITUTE	333 BOSTWICK AVE NE	GRAND RAPIDS	MI	49503	KENT	USA	Biomedical Research and Research Training	002	3	8/5/2025	NON-COMPETING CONTINUATION	$62,573
2025	2024	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	001	1	3/24/2025	NEW	$0
														Subtotal = $625,736

Issue Date FY: 2024 ( Subtotal = $537,379 )
2024	2024	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	000	1	2/9/2024	NEW	$472,620
2024	2024	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Biomedical Research and Research Training	001	1	7/26/2024	NEW	-$242,441
2024	2024	VAN ANDEL RESEARCH INSTITUTE	333 BOSTWICK AVE NE	GRAND RAPIDS	MI	49503	KENT	USA	Biomedical Research and Research Training	002	2	7/26/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$307,200
														Subtotal = $537,379

Grand Total All Awards = $1,726,278

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Mechanisms and Applications of RNA-mediated Enzymes in Translation and Immunity

Award Number: R35GM152081

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: 02/12/2024

PERIOD OF PERFORMANCE END DATE: 01/31/2029

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