Memory in Bacterial Responses to Fluctuating Stress
细菌对波动压力的反应的记忆
基本信息
- 批准号:9282447
- 负责人:
- 金额:$ 30.78万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-07-01 至 2020-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAlgorithmic AnalysisAntibiotic ResistanceAntibioticsBacteriaBiologicalCarbonCell SizeCell divisionCell physiologyCellsCerealsClinicalComplexCost MeasuresCosts and BenefitsCulture MediaCustomData SetDevicesEngineeringEnvironmentEnzymesEscherichia coliExposure toGene CombinationsGene ExpressionGene Expression RegulationGenerationsGenesGoalsGrowthImageImage AnalysisIndividualLaboratoriesMeasurementMeasuresMediatingMemoryMetabolicMetabolic stressMicrofluidic MicrochipsMicrofluidicsMicroscopeMicroscopyModelingMolecularMothersNutrientOperonPathway interactionsPeriodicityPhenotypePhysiologic pulsePhysiologicalPopulationPopulation DynamicsPopulation GrowthProcessProductionProliferatingProteinsRegimenRegulationResolutionResourcesSignal TransductionSourceSpottingsStarvationStressSystemTestingTimeWorkantimicrobialbasecell growth regulationcellular targetingcostdaughter celldesigndrug structureexperienceexperimental studygenetic pedigreeinsightkillingsmathematical modelmicroorganismmolecular pumpmonolayerpredictive modelingresponsesingle cell analysissynthetic biologysynthetic constructtumor
项目摘要
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 degrade it. In a continually fluctuating environment, the
process of turning genes on and off can be costly, especially under antibiotic exposures when
cells are rapidly killed if the response gene is off. Our work shows that bacteria combine their
responses with molecular memory mechanisms that allow cells to avoid the costs of frequent
gene regulation in a fluctuating environment.
The project will determine the conditions under which molecular memory is a beneficial strategy,
and by using a combination of synthetic biology, microfluidics, microscopy, and modeling, we
will experimentally perturb and measure the costs and benefits of memory. We will construct
bacterial strains with a range of memory levels, and perform competition experiments to
determine how cellular memory profiles are tuned to the external environment.
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 quantify tens of thousands of cells
over hundreds of generations, and thereby measure population dynamics in fluctuating
environments at a resolution that was previously unattainable.
We will use two different levels of modeling, including a coarse-grained approach in which
timescales and rate constants are the main parameters, and the goal is to predict the optimal
amount of memory for a given response and fluctuating environment; and a detailed, single cell
stochastic model, in which the process of cellular elongation and division is precisely quantified
and modeled under changing conditions. These two representations will address different
aspects of memory, and allow us to bridge from detailed laboratory measurements to the
general biological principles that underlie bacterial survival.
项目总结:
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
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专利数量(0)
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EDO L KUSSELL其他文献
EDO L KUSSELL的其他文献
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{{ truncateString('EDO L KUSSELL', 18)}}的其他基金
Gene Regulation and Memory in Bacterial Metabolism and Antibiotic Resistance
细菌代谢和抗生素耐药性中的基因调控和记忆
- 批准号:
10566736 - 财政年份:2023
- 资助金额:
$ 30.78万 - 项目类别:
Revealing Stochastic Switches in Bacteria: Theory, Modeling, and Experiments
揭示细菌中的随机开关:理论、建模和实验
- 批准号:
8538463 - 财政年份:2011
- 资助金额:
$ 30.78万 - 项目类别:
Revealing Stochastic Switches in Bacteria: Theory, Modeling, and Experiments
揭示细菌中的随机开关:理论、建模和实验
- 批准号:
8194768 - 财政年份:2011
- 资助金额:
$ 30.78万 - 项目类别:
Revealing Stochastic Switches in Bacteria: Theory, Modeling, and Experiments
揭示细菌中的随机开关:理论、建模和实验
- 批准号:
8727053 - 财政年份:2011
- 资助金额:
$ 30.78万 - 项目类别:
Revealing Stochastic Switches in Bacteria: Theory, Modeling, and Experiments
揭示细菌中的随机开关:理论、建模和实验
- 批准号:
8333393 - 财政年份:2011
- 资助金额:
$ 30.78万 - 项目类别:
Revealing Stochastic Switches in Bacteria: Theory, Modeling, and Experiments
揭示细菌中的随机开关:理论、建模和实验
- 批准号:
8916141 - 财政年份:2011
- 资助金额:
$ 30.78万 - 项目类别:
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