Mechanistic characterization of quantitative trait genetics affecting cell metabolism

影响细胞代谢的数量性状遗传学的机制表征

基本信息

批准号：
10596980
负责人：
BRUCE Bruce FUTCHER
金额：
$ 10万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10596980
关键词：
Affect Affinity Alleles Base Pairing Binding Binding Sites Biochemical Biological Models Biology Carbon Catabolism Cell physiology Cells Cellular Metabolic Process Chemicals Chromosome Mapping Code Coupled DNA DNA Sequence Data Dictionary Enzymes Evolution Gene Expression Gene Expression Regulation Genes Genetic Genetic Engineering Genetic Transcription Genetic Variation Genome Genomic Segment Genomics Glucose Glucose Transporter Goals Heritability Hexose Transporter Homeostasis Human Individual Label Lead Link Malignant Neoplasms Mammals Maps Mass Spectrum Analysis Measures Messenger RNA Metabolic Metabolic Pathway Methods Mutation Nature Nutrient Organism Outcome Phenotype Physiological Play Population Positioning Attribute Post-Transcriptional Regulation Post-Translational Regulation Proteins Proteomics Quantitative Trait Loci RNA Regulation Role Saccharomyces cerevisiae Sorting Structure Testing Time Translational Regulation Validation Variant Whole Organism Work Yeast Model System Yeasts causal variant cell growth cohort genetic analysis genetic variant genome wide association study genome-wide genomic locus glucose sensor glucose uptake mRNA Expression mRNA sequencing medical schools model organism protein degradation reaction rate respiratory tool trait transcription factor transcriptome sequencing uptake

Affect Affinity Alleles Base Pairing Binding Binding Sites Biochemical Biological Models Biology Carbon Catabolism Cell physiology Cells Cellular Metabolic Process Chemicals Chromosome Mapping Code Coupled DNA DNA Sequence Data Dictionary Enzymes Evolution Gene Expression Gene Expression Regulation Genes Genetic Genetic Engineering Genetic Transcription Genetic Variation Genome Genomic Segment Genomics Glucose Glucose Transporter Goals Heritability Hexose Transporter Homeostasis Human Individual Label Lead Link Malignant Neoplasms Mammals Maps Mass Spectrum Analysis Measures Messenger RNA Metabolic Metabolic Pathway Methods Mutation Nature Nutrient Organism Outcome Phenotype Physiological Play Population Positioning Attribute Post-Transcriptional Regulation Post-Translational Regulation Proteins Proteomics Quantitative Trait Loci RNA Regulation Role Saccharomyces cerevisiae Sorting Structure Testing Time Translational Regulation Validation Variant Whole Organism Work Yeast Model System Yeasts causal variant cell growth cohort genetic analysis genetic variant genome wide association study genome-wide genomic locus glucose sensor glucose uptake mRNA Expression mRNA sequencing medical schools model organism protein degradation reaction rate respiratory tool trait transcription factor transcriptome sequencing uptake

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项目摘要

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.

个体之间的DNA序列的自然变化是由于突变而发生的时间。 DNA序列的变化会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的糖疗，我们的小组已经确定了基因组的区域，其中差异在DNA序列中，会导致特定蛋白质水平的遗传差异与变化区域不同的基因。我们的重点是改变发生的蛋白质水平独立于为这些蛋白质编码的mRNA表达变化。我们将确定DNA序列中的特定基本对变化，这些变化负责更好了解DNA变化导致其他水平变化的机制蛋白质。我们发现以这种方式调节的许多蛋白质对于细胞对葡萄糖的摄取和分解代谢。我们将明确确定哪些DNA序列导致葡萄糖摄取率不同，以了解葡萄糖转运蛋白的摄取剂受监管。我们还将使用质谱化学分析来测量细胞并确定蛋白质水平的这些变化是否导致生长的变化单元格，或者这些差异中的某些差异是否是一种细胞制定的方式代谢稳态。