Regulation of Phospholipid Biosynthetic Genes in Yeast

酵母磷脂生物合成基因的调控

• 批准号: 1020987
• 负责人: John Lopes
• 金额: $ 59.94万
• 依托单位: University of Massachusetts Amherst
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1020987&HistoricalAwards=false
• 关键词: Regulation; Phospholipid; Biosynthetic; Genes; Yeast

The long-term goal of this project is to understand the regulation of phospholipid biosynthesis. The yeast, Saccharomyces cerevisiae, has been an outstanding model system for the study of this biological process. The primary mechanism for inositol-mediated repression of phospholipid biosynthetic gene expression employs the Opi1p repressor. Opi1p is tethered in the endoplasmic reticulum (ER) by association with phosphatidic acid (PA) under derepressing conditions. In the presence of inositol, PA levels drop and Opi1p translocates to the nucleus where it interacts with the Ino2p activator to repress transcription. Opi1p was first defined by the identification of overproduction and excretion of inositol (Opi-) mutants. These mutants are generally associated with constitutive derepressed expression of the phospholipid biosynthetic genes. The Lopes lab has reported a genomic screen that identified 91 Opi- mutants. The goal of this project is to define how the Opi- mutants affect regulation of phospholipid biosynthesis. Dr. Lopes will define the molecular role of each Opi- mutant by testing for several phenotypes. He will also determine the epistatic relationships between the Opi- mutants. Lastly, he will identify the Opi1p-independent PA-sensing mechanism. This research addresses two important biological processes, repression of gene expression and phospholipid biosynthesis.Broader Impacts: The project will serve as a training vehicle for graduate and undergraduate (UG) students. Dr Lopes has a track record of training UG students, many of whom have been authors on published manuscripts. The foundation for this project was published in Genetics and co-authored by an UG student. Many of the Graduate and UG students trained in the Lopes lab are women and members of groups under-represented in science. The results of the research will appeal to a broad research community and will be disseminated in peer-reviewed journals. Dr. Lopes has a track record of incorporating basic research into courses and genetic experiments in this project will be modules in a senior level undergraduate laboratory.

本项目的长期目标是了解磷脂生物合成的调节。 酵母，酿酒酵母，一直是一个杰出的模型系统，为研究这一生物过程。 肌醇介导的磷脂生物合成基因表达抑制的主要机制采用Opi 1 p抑制子。 Opi 1 p在去抑制条件下通过与磷脂酸（PA）结合而被束缚在内质网（ER）中。 在肌醇的存在下，PA水平下降，Opi 1 p易位到细胞核，在那里它与Ino 2 p激活剂相互作用以抑制转录。 Opi 1 p最初是通过鉴定肌醇（Opi-）突变体的过量生产和排泄来定义的。 这些突变体通常与磷脂生物合成基因的组成性去阻遏表达相关。 Lopes实验室报道了一项基因组筛选，鉴定了91种Opi突变体。 本项目的目标是确定Opi突变体如何影响磷脂生物合成的调节。 Lopes博士将通过测试几种表型来定义每个Opi突变体的分子作用。 他还将确定Opi突变体之间的上位关系。 最后，他将确定Opi 1 p独立的PA传感机制。 这项研究解决了两个重要的生物过程，基因表达和磷脂biosynthesis.Broader影响的抑制：该项目将作为研究生和本科生（UG）学生的培训工具。 Lopes博士在培训UG学生方面有着良好的记录，其中许多人都是已发表手稿的作者。 该项目的基础发表在遗传学上，由UG学生合著。 许多在洛佩斯实验室接受培训的研究生和UG学生都是女性和科学代表性不足的群体的成员。 研究结果将吸引广泛的研究界，并将在同行评审的期刊上传播。 Lopes博士有将基础研究纳入课程的记录，该项目的遗传实验将成为高级本科实验室的模块。