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

> **NIH NIH R01** · YALE UNIVERSITY · 2022 · $359,452

## Abstract

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.

## Key facts

- **NIH application ID:** 10131213
- **Project number:** 5R01GM127870-04
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Murat Acar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $359,452
- **Award type:** 5
- **Project period:** 2018-06-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10131213

## Citation

> US National Institutes of Health, RePORTER application 10131213, Microfluids-enabled Quantitative Systems Biology Approaches to Construct Gene Networks Regulating Yeast Lifespan and Genetic Noise Dynamics During Aging (5R01GM127870-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10131213. Licensed CC0.

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