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Gene Regulation and Memory in Bacterial Metabolism and Antibiotic Resistance

Award Number: R01GM148703
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: 01/01/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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Gene Regulation and Memory in Bacterial Metabolism and Antibiotic Resistance - Project Summary: Bacterial cells have a repertoire of responses that can be used to survive under different types of environmental stress. Changes in carbon sources cause cells to turn on specific metabolic genes, which are later repressed when those sources are depleted. Antibiotic exposure can trigger the expression of molecular pumps that remove the antibiotic from the cell, or the production of enzymes that specifically inactivate or degrade it. In a continually fluctuating environment, the process of turning genes on and off can be inefficient and cause growth lags. Our work shows that bacteria combine their responses with phenotypic memory – the passage of stable proteins from mother to daughter cells – which allows cells to avoid growth lags in fluctuating environments. Using a combination of quantitative microbiology, microfluidics, microscopy, sequencing, and modeling, we will study the costs and benefits of gene regulation in fluctuating environments. We will measure and model the fitness landscape of phenotypic memory using a library of strains with perturbed memory levels. Competition experiments in fluctuating environments will be used to test biophysical and population dynamics models. We present an innovative modular system that enables direct comparison of different gene regulatory strategies – including responsive, bistable, and constitutive regulation – for any gene of interest. We apply the system to study different classes of antibiotic resistance mechanisms. The proposed experiments make use of a custom-built microfluidic ‘chemoflux’ system that we developed, in which bacterial populations grow in monolayers, tracked at single cell resolution under the microscope, while the growth media can be arbitrarily fluctuated in time. Using the chemoflux and our image analysis algorithms, we are able to simultaneously track hundreds of independent bacterial populations, and thereby measure population dynamics in fluctuating environments. We combine experiments with biophysical modeling to gain insights into the costs and benefits of gene regulation and memory. Models are parameterized using experimental data in a wide range of conditions, and rigorously tested by their predictions on competition experiments in fluctuating environments. The range of experiments and modeling employed address different aspects of gene regulation and memory, and allows us to bridge from detailed laboratory measurements to the general biological principles that underlie bacterial survival.


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 = $322,854 )
2026	2026	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Biomedical Research and Research Training	000	4	12/8/2025	NON-COMPETING CONTINUATION	$290,569
2026	2026	NEW YORK UNIVERSITY	70 WASHINGTON SQ S FL 11	NEW YORK	NY	10012	NEW YORK	USA	Biomedical Research and Research Training	001	4	3/18/2026	NON-COMPETING CONTINUATION	$32,285
														Subtotal = $322,854

Issue Date FY: 2025 ( Subtotal = $323,110 )
2025	2025	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Biomedical Research and Research Training	000	3	11/19/2024	NON-COMPETING CONTINUATION	$290,799
2025	2025	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Biomedical Research and Research Training	001	3	8/8/2025	NON-COMPETING CONTINUATION	$32,311
														Subtotal = $323,110

Issue Date FY: 2024 ( Subtotal = $323,359 )
2024	2024	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Biomedical Research and Research Training	000	2	11/2/2023	NON-COMPETING CONTINUATION	$291,023
2024	2024	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Biomedical Research and Research Training	001	2	6/18/2024	NON-COMPETING CONTINUATION	$32,336
														Subtotal = $323,359

Issue Date FY: 2023 ( Subtotal = $308,657 )
2023	2023	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Biomedical Research and Research Training	000	1	12/27/2022	NEW	$308,657
														Subtotal = $308,657

Grand Total All Awards = $1,277,980

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Gene Regulation and Memory in Bacterial Metabolism and Antibiotic Resistance

Award Number: R01GM148703

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: 01/01/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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