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Biophysical models and mechanisms for cellular adaptation to environmental stress

Award Number: R35GM143042
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: 08/01/2021
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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Biophysical models and mechanisms for cellular adaptation to environmental stress - Project Summary/Abstract Living cells possess the remarkable ability to adapt to changes in their environmental conditions. Adaptation involves changes in cellular properties in response to external cues in order to regulate vital physiological functions and processes. While much progress has been made in identifying the molecular components and biochemical pathways underlying cellular stress response, the role of cellular physical properties in adaptive stress response is mostly unknown. Our recent studies provide evidence that changes in cell shape and cellular physical properties promotes adaptive benefits in certain stressful conditions via mechanochemical feedback processes. The goal of the proposed research is to develop quantitative theory and data-driven computational models to uncover the biophysical feedback mechanisms underlying cellular adaptive response to environmental stresses. We will utilize an interdisciplinary approach that integrates tools from statistical physics, systems biology, and experimental data analysis to construct predictive models for cell behavior. We will specifically investigate adaptive response in two different biological systems: 1) adaptation to nutrient shifts and antibiotic stresses in proliferating bacterial cells, and 2) adaptation to energy deprivation and cell state transitions in nematode worm embryos. In each of these systems we will develop quantitative cell-level models based on known molecular circuits, intracellular biophysical interactions and dynamics observed in experimental data. The models will be calibrated and tested against quantitative single-cell data obtained from our experimental collaborators. The resultant models will help test different experimental hypotheses, isolate and test the relative roles of biochemical and physical pathways in cellular adaptive response, and pinpoint the main driving forces behind complex adaptive phenomena. In addition to developing quantitative models for cellular biophysical behaviors, our study will generate a variety of computational tools that will enable efficient whole-cell simulations of bacterial growth, morphogenesis, intracellular organization and single-cell development.


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 = $0 )
2026	2025	GEORGIA TECH RESEARCH CORP	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Biomedical Research and Research Training	000	6	3/4/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $374,095 )
2025	2025	GEORGIA TECH RESEARCH CORP	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Biomedical Research and Research Training	003	6	8/14/2025	NON-COMPETING CONTINUATION	$342,827
2025	2024	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	002	4	7/8/2025	NON-COMPETING CONTINUATION	$0
2025	2024	GEORGIA TECH RESEARCH CORP	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Biomedical Research and Research Training	001	5	6/17/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$341,081
2025	2024	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	4	6/17/2025	NON-COMPETING CONTINUATION	-$309,813
														Subtotal = $374,095

Issue Date FY: 2024 ( Subtotal = $309,814 )
2024	2024	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	4	5/15/2024	NON-COMPETING CONTINUATION	$309,814
														Subtotal = $309,814

Issue Date FY: 2023 ( Subtotal = $310,641 )
2023	2023	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	3	6/15/2023	NON-COMPETING CONTINUATION	$310,641
														Subtotal = $310,641

Issue Date FY: 2022 ( Subtotal = $311,443 )
2022	2022	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	2	5/16/2022	NON-COMPETING CONTINUATION	$311,443
														Subtotal = $311,443

Issue Date FY: 2021 ( Subtotal = $312,220 )
2021	2021	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	1	7/29/2021	NEW	$312,220
														Subtotal = $312,220

Grand Total All Awards = $1,618,213

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Biophysical models and mechanisms for cellular adaptation to environmental stress

Award Number: R35GM143042

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: 08/01/2021

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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