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：
10360524
负责人：
BRUCE Bruce FUTCHER
金额：
$ 33.19万
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 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10360524
关键词：
Affect Affinity Alleles Animal Model Base Pairing Binding Binding Sites Biochemical Biological Models Biology Carbon Catabolism Cell physiology Cells Cellular Metabolic Process Chemicals 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 - Cell Movement Structure Testing Time Translational Regulation Translations Validation Variant Whole Organism Work Yeast Model System Yeasts base 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 protein degradation reaction rate respiratory tool trait transcription factor transcriptome sequencing uptake

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 DNA 序列的自然变异是由于基因突变造成的时间。 DNA 序列的变化可能导致最终结果的差异，或者携带这些遗传变异的个体的表型。使用模型酵母酿酒酵母，我们的小组已经确定了基因组中存在差异的区域 DNA序列的改变导致特定蛋白质水平的可遗传差异与变化区域不同的基因。我们的重点是蛋白质水平发生的变化与编码这些蛋白质的 mRNA 表达的变化无关。我们将确定 DNA 序列中特定碱基对的变化，这些变化有助于更好地了解 DNA 变化导致其他物质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。我们将具体鉴定哪些DNA序列导致不同的葡萄糖摄取率，以了解葡萄糖转运蛋白的作用受监管。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会导致细胞生长的变化细胞，或者这些差异是否是细胞发挥作用的一种方式代谢稳态。