Mechanistic characterization of quantitative trait genetics affecting cell metabolism
Mechanistic characterization of quantitative trait genetics affecting cell metabolism
批准号:
9893888
负责人:
Adam Phillip Rosebrock
金额:
$33.19万
依托单位国家:
美国
项目类别:
财政年份:
2019
资助国家:
美国
项目状态:
已结题
起止时间:
2019-04-01 至 2024-03-31
关键词:
AffectAffinityAllelesAnimal ModelBase PairingBindingBinding SitesBiochemicalBiological ModelsBiologyCarbonCatabolismCell physiologyCellsCellular Metabolic ProcessChemicalsCodeCoupledDNADNA SequenceDataDictionaryEnzymesEvolutionGene ExpressionGene Expression RegulationGenesGeneticGenetic EngineeringGenetic TranscriptionGenetic VariationGenomeGenomic SegmentGenomicsGlucoseGlucose TransporterGoalsHeritabilityHexose TransporterHomeostasisHumanIndividualLabelLeadLinkMalignant NeoplasmsMammalsMapsMass Spectrum AnalysisMeasuresMessenger RNAMetabolicMetabolic PathwayMethodsMutationNatureNutrientOrganismOutcomePhenotypePhysiologicalPlayPopulationPositioning AttributePost-Transcriptional RegulationPost-Translational RegulationProteinsProteomicsQuantitative Trait LociRNARegulationRoleSaccharomyces cerevisiaeSorting - Cell MovementStructureTestingTimeTranslational RegulationTranslationsValidationVariantWhole OrganismWorkYeast Model SystemYeastsbasecausal variantcell growthcohortgenetic analysisgenetic variantgenome wide association studygenome-widegenomic locusglucose sensorglucose uptakemRNA ExpressionmRNA sequencingmedical schoolsprotein degradationreaction raterespiratorytooltraittranscription factortranscriptome sequencinguptake
中文摘要
个体之间DNA序列的自然变异是由于基因突变的结果。
时间DNA序列的变异可能导致最终结果的差异,或
表型,携带这些遗传变异的个体。使用模型酵母
酿酒酵母,我们的小组已经确定了基因组中的差异区域,
在DNA序列中的差异导致了特定蛋白质水平的遗传差异,
与改变的区域不同的基因。我们的重点是蛋白质水平的变化,
而与编码这些蛋白质的mRNA表达的变化无关。我们将
确定DNA序列中负责更好地
了解DNA的变化导致其他蛋白质水平变化的机制
proteins.我们发现的许多以这种方式调节的蛋白质是细胞生长所必需的。
细胞对葡萄糖的摄取和催化。我们会特别确定哪些DNA序列
导致不同的葡萄糖摄取率,以了解葡萄糖转运蛋白是如何
监管.我们还将使用质谱化学分析来测量
细胞,并确定这些蛋白质水平的变化是否会导致细胞生长的变化。
或者这些差异是否是细胞
代谢平衡
英文摘要
Natural variation in DNA sequences between individuals occurs as a result of mutations over
time. Variations in DNA sequence can lead to differences in the ultimate outcome, or
phenotype, of the individual carrying these genetic variants. Using the model yeast
Saccharomyces cerevisiae, our group has identified regions of the genome in which differences
in DNA sequence result in heritable differences in the level of specific proteins that are made by
genes distinct from the changed regions. Our focus is on changes to protein levels that occur
independently of changes in expression of the mRNAs that code for these proteins. We will
identify the specific base-pair changes in DNA sequence that are responsible to better
understand the mechanisms by which changes in DNA lead to changes in the level of other
proteins. Many of the proteins we found to be regulated in this way are necessary for the
uptake and catabolism of glucose by cells. We will specifically identify which DNA sequences
lead to different rates of glucose uptake in order to understand how glucose transporters are
regulated. We will also use mass spectrometry chemical analysis to measure the contents of
cells and determine whether these changes in protein level lead to changes in the growth of
cells, or alternatively whether some of these differences are a way by which cells enact
metabolic homeostasis.
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