Regulation of Phospholipid Biosynthetic Genes in Yeast

这个项目的长期目标是了解磷脂生物合成的调节。酿酒酵母是研究这一生物过程的优秀模型系统。肌醇介导的抑制磷脂生物合成基因表达的主要机制是利用Opi1p抑制物。在减压条件下，Opi1p通过与磷脂酸(PA)结合被拴在内质网(ER)。在肌醇存在的情况下，PA水平下降，Opi1p移位到细胞核，在那里它与Ino2p激活剂相互作用，抑制转录。Opi1p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结构性去抑制表达有关。洛佩斯实验室报告了一个基因组筛查，发现了91个OPI突变体。这个项目的目标是确定OPI突变体如何影响磷脂生物合成的调节。洛佩斯博士将通过测试几种表型来确定每个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Opi1p不依赖PA的传感机制。这项研究涉及两个重要的生物学过程，基因表达的抑制和磷脂的生物合成。广泛的影响：该项目将作为研究生和本科生的培训工具。洛佩斯博士有培训UG学生的记录，其中许多人是已发表手稿的作者。这个项目的基础发表在《遗传学》杂志上，并由UG的一名学生与人合著。许多在洛佩斯实验室接受培训的研究生和UG学生都是女性和在科学界代表性不足的团体的成员。研究结果将吸引广泛的研究界，并将在同行评议的期刊上传播。洛佩斯博士有将基础研究纳入课程的记录，该项目中的遗传学实验将成为高级本科生实验室的模块。

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.