Collaborative Research: The Causes of Natural Variation in Protein Expression

合作研究：蛋白质表达自然变异的原因

• 批准号: 1517482
• 负责人: Scott Rifkin
• 金额: $ 33.89万
• 依托单位: University of California-San Diego
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-15 至 2019-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1517482&HistoricalAwards=false
• 关键词: Collaborative; Research; Causes; Natural; Variation

The goal of this project is to understand how the genetic material of a cell, its DNA, controls the amount of protein each cell produces, how a cell's environment stimulates it to ramp protein production up or down, and how this response differs between individuals. To function, an organism copies specific genetic information from genes in its DNA to molecules called RNA and then uses that RNA as templates to make proteins. Proteins are the molecular machines that carry out the work of cells and give cells their identities. It is not clear what causes the amount of protein that cells make to differ between individuals. It is known that this can be caused by differences in how much RNA is made. However, individuals may differ in how fast they make protein from the same amount of RNA and also how quickly they recycle protein when it gets old. The research will measure RNA and protein levels in two different strains of budding yeast as they respond to mating pheromone. It will involve both broad surveys of many proteins and detailed measurements of a targeted set. While engaging in this research, students at a primarily undergraduate institution and a postdoctoral fellow will gain interdisciplinary training in the emerging field of evolutionary systems biology. Students from a junior high school will also be engaged in scientific discovery; they will collect wild yeasts from the air and from tree bark and identify their relationships to each other in the fungal tree of life, fulfilling the requirements of the Next Generation Science Standards recently adopted by California and Washington.Specifically, the project seeks to systematically characterize the causes of divergence in protein expression temporal dynamics using a unique combination of high-throughput phenotyping, modeling, cellular resolution quantitative trait mapping, and targeted functional analysis. The mating pheromone response network of the budding yeast Saccharomyces cerevisiae will be used as a model system. The research will identify the contribution of variation in mRNA levels, protein production rates, and protein degradation rates to protein levels. Applying this approach to a network of genes will elucidate the general trends in how protein expression variation arises. Identifying the causal polymorphisms underlying protein expression variation will point to the molecular mechanisms for such variation. These project outcomes will have far reaching effects in the fields of evolutionary genetics and systems biology.

这个项目的目标是了解细胞的遗传物质，它的DNA，如何控制每个细胞产生的蛋白质的量，细胞的环境如何刺激它增加或减少蛋白质的产生，以及这种反应在个体之间有何不同。为了发挥功能，生物体将特定的遗传信息从其DNA中的基因复制到称为RNA的分子中，然后使用该RNA作为模板来制造蛋白质。蛋白质是执行细胞工作并赋予细胞身份的分子机器。目前尚不清楚是什么原因导致细胞产生的蛋白质数量在个体之间存在差异。据了解，这可能是由于RNA的合成量不同造成的。然而，个体可能在从相同数量的RNA中制造蛋白质的速度以及蛋白质老化时回收的速度方面存在差异。这项研究将测量两种不同的芽殖酵母菌株对交配信息素反应时的RNA和蛋白质水平。它将涉及许多蛋白质的广泛调查和目标集的详细测量。在从事这项研究的同时，主要是本科院校的学生和博士后研究员将获得进化系统生物学新兴领域的跨学科培训。初中的学生也将从事科学发现;他们将从空气和树皮中收集野生酵母，并确定它们在真菌生命树中的相互关系，以满足加州和华盛顿最近通过的下一代科学标准的要求。具体来说，该项目试图系统地表征蛋白质表达时间动态差异的原因，使用高通量表型分析，建模，细胞分辨率定量性状作图和靶向功能分析。芽殖酵母酿酒酵母的交配信息素反应网络将被用作模型系统。该研究将确定mRNA水平、蛋白质产生速率和蛋白质降解速率的变化对蛋白质水平的贡献。将这种方法应用于基因网络将阐明蛋白质表达变异如何出现的一般趋势。确定蛋白质表达变异的原因多态性将指向这种变异的分子机制。这些项目成果将在进化遗传学和系统生物学领域产生深远影响。