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Microfluids-enabled Quantitative Systems Biology Approaches to Construct Gene Networks Regulating Yeast Lifespan and Genetic Noise Dynamics During Aging

Award Number: R01GM127870
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: 06/01/2018
PERIOD OF PERFORMANCE END DATE: 11/30/2022

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Microfluids-enabled Quantitative Systems Biology Approaches to Construct Gene Networks Regulating Yeast Lifespan and Genetic Noise Dynamics During Aging - ABSTRACT Aging is the primary cause of chronic human morbidity and mortality. Interventions targeting key proteins that extend healthy lifespan at the cellular and organismal level are therefore desirable. Genetic changes that extend lifespan in model organisms often delay the onset of age-related morbidity and exhibit evolutionary conservation in higher organisms. Cells typically use gene networks to coordinate their response to stimuli, and thus the dynamics of cellular aging is also likely governed at the gene network level. However, little is known about the composition of such an aging network both in terms of the genes involved and their relationship within the network. By performing high-throughput measurements of yeast replicative lifespan in a microfluidic device, this proposal aims to identify and functionally compartmentalize the genetic components of novel aging modules based on the strength of epistatic interactions. Furthermore, it aims to elucidate the impact of these network modules on noise reduction during aging, an emergent property of single-cell aging. Key components of the aging modules as well as genes from a chromatin-remodeling network will be deleted from the yeast genome and the resulting changes in genetic noise dynamics will be measured using the activity of the canonical GAL1 promoter as a model in single yeast cells. Finally, expression strength changes of the key genes composing the aging modules will be followed experimentally during cellular aging with the goal of exploring how aging alters the plasticity of network nodes. Successful completion of this project will provide novel links between replicative lifespan and the collective phenotype of gene expression noise in the context of newly identified network modules governing how single yeast cells age in real time.


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: 2023 ( Subtotal = $0 )
2023	2022	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Biomedical Research and Research Training	000	4	11/25/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $359,452 )
2022	2022	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Biomedical Research and Research Training	000	4	11/18/2021	NON-COMPETING CONTINUATION	$323,507
2022	2022	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Biomedical Research and Research Training	001	4	5/19/2022	NON-COMPETING CONTINUATION	$35,945
														Subtotal = $359,452

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2020	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Biomedical Research and Research Training	000	3	6/7/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $368,646 )
2020	2020	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Biomedical Research and Research Training	000	3	3/20/2020	NON-COMPETING CONTINUATION	$368,646
														Subtotal = $368,646

Issue Date FY: 2019 ( Subtotal = $377,885 )
2019	2019	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Biomedical Research and Research Training	000	2	3/2/2019	NON-COMPETING CONTINUATION	$377,885
														Subtotal = $377,885

Issue Date FY: 2018 ( Subtotal = $386,233 )
2018	2018	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Biomedical Research and Research Training	000	1	5/31/2018	NEW	$386,233
														Subtotal = $386,233

Grand Total All Awards = $1,492,216

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Microfluids-enabled Quantitative Systems Biology Approaches to Construct Gene Networks Regulating Yeast Lifespan and Genetic Noise Dynamics During Aging

Award Number: R01GM127870

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: 06/01/2018

PERIOD OF PERFORMANCE END DATE: 11/30/2022

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