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Genome exploration through toxin-mediated ribosome stalling

Award Number: R01AI154464
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/07/2020
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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Genome exploration through toxin-mediated ribosome stalling - Project Summary Approximately 90% of individuals infected with Mycobacterium tuberculosis (Mtb) develop an asymptomatic latent infection, which is non-infectious. Although some individuals may eradicate this infection, those who do not comprise a large reservoir of persons who can convert from latent to active TB, which is infectious. Reactivation is especially likely in immune-compromised individuals, including those infected with HIV. The molecular switches that enable Mtb to slow or stop replication, become dormant and establish latent TB infection are poorly characterized. A thorough understanding of these switches is critical for development of 1) diagnostics to enable prediction of reactivation risk and 2) shorter, more effective treatment regimens for latent TB infection. Toxin-antitoxin (TA) systems are strongly implicated in establishment of latent TB infection because their toxin components typically downregulate Mtb cell growth and are activated in response to stresses relevant to this state. Yet, the extraordinary redundancy of TA systems make determination of the individual contributions of each toxin challenging using conventional genetic and molecular biological approaches. We propose to use a powerful battery of genome-scale tools to track the fate of transcripts, ribosomes and proteins in response to activation of a subset of tRNA-cleaving toxins to understand the molecular mechanisms that underlie stress survival. We then exploit our finding that the codon-specific ribosome-stalling characteristic of these toxins identifies novel ORFs and apply this as a reliable tool for improved Mtb genome annotation.


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 = $0 )
2025	2023	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Allergy and Infectious Diseases Research	000	4	3/21/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Allergy and Infectious Diseases Research	002	4	12/19/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$520,302
2024	2022	RUTGERS, THE STATE UNIVERSITY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Allergy and Infectious Diseases Research	001	3	12/19/2023	NON-COMPETING CONTINUATION	-$383,768
2024	2021	RUTGERS, THE STATE UNIVERSITY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Allergy and Infectious Diseases Research	000	2	12/19/2023	NON-COMPETING CONTINUATION	-$136,534
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $383,821 )
2023	2023	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Allergy and Infectious Diseases Research	001	4	4/20/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$383,821
2023	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Allergy and Infectious Diseases Research	000	3	4/20/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $383,821

Issue Date FY: 2022 ( Subtotal = $383,768 )
2022	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Allergy and Infectious Diseases Research	000	3	5/2/2022	NON-COMPETING CONTINUATION	$383,768
														Subtotal = $383,768

Issue Date FY: 2021 ( Subtotal = $379,916 )
2021	2021	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Allergy and Infectious Diseases Research	000	2	4/21/2021	NON-COMPETING CONTINUATION	$379,916
														Subtotal = $379,916

Issue Date FY: 2020 ( Subtotal = $377,402 )
2020	2020	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Allergy and Infectious Diseases Research	000	1	5/6/2020	NEW	$377,402
														Subtotal = $377,402

Grand Total All Awards = $1,524,907

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Genome exploration through toxin-mediated ribosome stalling

Award Number: R01AI154464

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/07/2020

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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