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Evolution and Regulation of Bacterial Proteome Composition

Award Number: R35GM124732
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: 09/01/2017
PERIOD OF PERFORMANCE END DATE: 01/31/2028

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Evolution and Regulation of Bacterial Proteome Composition - Project Summary/Abstract The proteome is a quantitative output of a genome and the ultimate effector of cellular functions. Yet remarkably little is known about the logic behind proteome construction. The goal of my research program is to understand the evolutionary driving forces and the molecular processes that shape protein levels in living cells. Using bacterial model systems, my lab takes a holistic approach by developing quantitative technologies to measure, manipulate, and model the expression stoichiometry of co-regulated proteins and the effect of imbalanced production on bacterial growth, survival, and colonization. This current grant seeks to answer several fundamental questions regarding the physiology and regulation of protein stoichiometry. At the physiological level, we use molecular and theoretical methods to determine 1) the optimality of protein production rates for every gene and the cellular responses to non-optimal levels, 2) the precise ratios of protein production upon sudden environmental changes and the consequences of imbalanced production, and 3) the theoretical basis for the stoichiometry of proteins that function together. These studies will help elucidate new principles for building a proteome and provide a new way of thinking about protein imbalance in disease. To understand the regulatory principles of gene expression behind this stoichiometric protein production, we use quantitative and massively parallel assays to determine 1) the sequence determinant of Rho- dependent transcription termination in Bacillus subtilis, whose RNAP polymerases outpace ribosomes (`runaway transcription'), 2) the molecular basis of runaway transcription, 3) a predictive model for the efficiency of Rho-independent transcription termination, and 4) the landscape of translational control for bacteriophage mRNAs. Our studies in these areas will help establish a critically needed framework for predicting gene expression from genomic sequences and advance fundamental knowledge of bacterial gene regulation. We anticipate that our mechanistic dissection, coupled with systems-level inquiry into proteome composition, will make bacterial model organisms the first system for which we have a quantitative understanding of the interplay between genome, proteome, and fitness.


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 = $468,870 )
2025	2025	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Biomedical Research and Research Training	001	8	4/30/2025	NON-COMPETING CONTINUATION	$468,870
2025	2024	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Biomedical Research and Research Training	000	7	11/11/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $468,870

Issue Date FY: 2024 ( Subtotal = $468,870 )
2024	2024	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Biomedical Research and Research Training	000	7	1/4/2024	NON-COMPETING CONTINUATION	$421,983
2024	2024	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Biomedical Research and Research Training	003	7	6/19/2024	NON-COMPETING CONTINUATION	$46,887
2024	2023	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Biomedical Research and Research Training	002	6	4/26/2024	COMPETING CONTINUATION	$2,564
2024	2021	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Biomedical Research and Research Training	001	5	4/26/2024	NON-COMPETING CONTINUATION	-$2,564
														Subtotal = $468,870

Issue Date FY: 2023 ( Subtotal = $468,870 )
2023	2023	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Biomedical Research and Research Training	000	6	1/30/2023	COMPETING CONTINUATION	$468,870
														Subtotal = $468,870

Issue Date FY: 2021 ( Subtotal = $386,750 )
2021	2021	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Biomedical Research and Research Training	000	5	8/20/2021	NON-COMPETING CONTINUATION	$386,750
														Subtotal = $386,750

Issue Date FY: 2020 ( Subtotal = $386,750 )
2020	2020	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Biomedical Research and Research Training	000	4	8/24/2020	NON-COMPETING CONTINUATION	$386,750
														Subtotal = $386,750

Issue Date FY: 2019 ( Subtotal = $444,721 )
2019	2019	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Biomedical Research and Research Training	000	3	8/29/2019	NON-COMPETING CONTINUATION	$386,750
2019	2019	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Biomedical Research and Research Training	001	3	9/3/2019	SUPPLEMENT FOR EXPANSION	$57,971
														Subtotal = $444,721

Issue Date FY: 2018 ( Subtotal = $386,750 )
2018	2018	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Biomedical Research and Research Training	000	2	8/30/2018	NON-COMPETING CONTINUATION	$386,750
														Subtotal = $386,750

Issue Date FY: 2017 ( Subtotal = $281,088 )
2017	2017	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Biomedical Research and Research Training	000	1	8/31/2017	NEW	$281,088
														Subtotal = $281,088

Grand Total All Awards = $3,292,669

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Evolution and Regulation of Bacterial Proteome Composition

Award Number: R35GM124732

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: 09/01/2017

PERIOD OF PERFORMANCE END DATE: 01/31/2028

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