Mechanistic characterization of quantitative trait genetics affecting cell metabolism

DNA序列在个体之间的自然变异是由于 时间到了。DNA序列的变化可能会导致最终结果的不同，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，我们的团队已经确定了基因组中存在差异的区域 在DNA序列中导致特定蛋白质水平的可遗传差异 不同于变化区域的基因。我们的重点是蛋白质水平的变化 与编码这些蛋白质的mRNAs的表达变化无关。我们会 识别DNA序列中的特定碱基对变化，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。我们发现的许多以这种方式调节的蛋白质是 细胞对葡萄糖的吸收和分解代谢。我们将具体识别哪些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 受监管的。我们还将使用质谱仪化学分析来测量 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 或者这些差异中的一些是否是细胞制定的一种方式 代谢动态平衡。

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.