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Regulation and Physiological Roles of Translational Fidelity

Award Number: R35GM136213
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: 06/01/2020
PERIOD OF PERFORMANCE END DATE: 05/31/2025

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Regulation and Physiological Roles of Translational Fidelity - PROJECT SUMMARY Accurate translation of the genetic information from messenger RNA to protein depends on multiple quality control mechanisms, which collectively maintain the average levels of translational errors at 10-4 for amino acid misincorporation (missense errors) and 10-2 for stop codon readthrough. However, increasing evidence shows that such translational fidelity is not fixed, but is rather affected by various environmental cues and genetic factors. Currently, we are only beginning to understand the regulatory networks leading to the fluctuation of translational fidelity during environmental changes and the resulting physiological responses. Translational errors can lead to reduced fitness, such as growth defects in bacteria and neurodegeneration in mammals, but may also benefit cells under certain stress conditions. Recently, we have shown that translational error rates vary from cell to cell in a genetically-identical bacterial population, raising the interesting question as to how fluctuation of translational errors affects the behavior of individual cells. In my laboratory, we are interested in developing and applying new technologies to understand the regulation and physiological roles of translational fidelity at both the population and single-cell levels. We are using our recently developed high-throughput reporter system to screen for conditions that alter translational fidelity, and have already identified novel environmental and genetic factors that are critical for this process. Next, we will determine the underlying mechanisms and expand our screens. Another research direction is to study how translational fidelity affects bacteria-host interactions, which is poorly understood. Our recent work reveals that either decreasing or increasing translational fidelity impairs expression of virulence genes and motility in Salmonella, suggesting that an optimal level of translational errors benefit bacteria during host interactions. We will further determine the regulatory networks using population and single- cell approaches. These studies will provide important insights into the roles of translational fidelity in environmental adaption and the regulatory mechanisms.


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	2024	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	000	5	11/6/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $395,302 )
2024	2024	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	001	5	5/14/2024	SUPPLEMENT FOR EXPANSION	$12,960
2024	2024	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	000	5	5/13/2024	NON-COMPETING CONTINUATION	$382,342
														Subtotal = $395,302

Issue Date FY: 2023 ( Subtotal = $460,097 )
2023	2023	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	001	4	5/10/2023	SUPPLEMENT FOR EXPANSION	$77,755
2023	2023	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	000	4	5/9/2023	NON-COMPETING CONTINUATION	$382,342
														Subtotal = $460,097

Issue Date FY: 2022 ( Subtotal = $447,138 )
2022	2022	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	000	3	5/9/2022	NON-COMPETING CONTINUATION	$382,342
2022	2022	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	001	3	8/5/2022	SUPPLEMENT FOR EXPANSION	$64,796
														Subtotal = $447,138

Issue Date FY: 2021 ( Subtotal = $382,342 )
2021	2021	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	000	2	5/18/2021	NON-COMPETING CONTINUATION	$382,342
														Subtotal = $382,342

Issue Date FY: 2020 ( Subtotal = $305,874 )
2020	2020	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	000	1	5/18/2020	NEW	$305,874
														Subtotal = $305,874

Grand Total All Awards = $1,990,753

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Regulation and Physiological Roles of Translational Fidelity

Award Number: R35GM136213

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: 06/01/2020

PERIOD OF PERFORMANCE END DATE: 05/31/2025

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