Microfluids-enabled Quantitative Systems Biology Approaches to Construct Gene Networks Regulating Yeast Lifespan and Genetic Noise Dynamics During Aging
Microfluids-enabled Quantitative Systems Biology Approaches to Construct Gene Networks Regulating Yeast Lifespan and Genetic Noise Dynamics During Aging
批准号:
9884605
负责人:
Murat Acar
金额:
$36.86万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-06-01 至 2022-11-30
关键词:
AffectAge of OnsetAgingAlgorithmsAnimal ModelBiological ProcessBiology of AgingCell AgingCellsChronicComplexDataEnvironmentEukaryotaExhibitsFoundationsGalactoseGalectin 1Gene ExpressionGenesGeneticGenetic EpistasisGenetic TranscriptionGoalsHumanInterventionLightLinkLongevityMeasurementMeasuresMicrofluidic MicrochipsMicrofluidicsModelingMorbidity - disease rateMutationNatureNetwork-basedNoiseOrganismPhenotypePropertyProteinsReporterStimulusStructureSystems BiologyTimeVariantYeastsage relatedbasecell agechromatin remodelingdesignexperimental studygene functionhuman morbidityhuman mortalitynovelpromoterresponseyeast genome
中文摘要
摘要
英文摘要
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.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Quantitative real-time characterization of single-cell aging: from phenotypes to
-
批准号:8757405
-
项目类别:
-
资助金额:$249.75万
-
财政年份:2014
-
负责人:Murat Acar
-
依托单位:
海外基金