Genomic analysis of phosphatidylinositol synthesis in yeast

酵母中磷脂酰肌醇合成的基因组分析

• 批准号: 0415511
• 负责人: John Lopes
• 金额: --
• 依托单位: Wayne State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0415511&HistoricalAwards=false
• 关键词: Genomic; analysis; phosphatidylinositol; synthesis; yeast

The long-range goal of the Lopes lab is to understand the regulation of phospholipid biosynthesis in eukaryotes using Saccharomyces cerevisiae as a model system. This project is focused on regulation of PIS1 expression. This gene is required for the synthesis of phosphatidylinositol (PI). PI and its metabolites play important roles in a myriad of processes, including: chromatin remodeling, export of mRNA from the nucleus, vesicle trafficking, and signal transduction. In spite of the importance of PI to the cell, relatively little is known about how its levels are regulated. This project tests the hypothesis that multiple cellular processes are coordinated with the synthesis of PI. To address this hypothesis, a genomic analysis of PI biosynthesis will be conducted. By screening a yeast gene deletion set, the Lopes lab previously identified 120 genes that affect expression of a PIS1 reporter. These genes suggest that processes such as peroxisomal function and DNA repair are coordinated with PI synthesis. The role in PI biosynthesis will be determined for a select set of these genes, and which among the five PIS1 promoter elements required for their action will be identified. The direct regulators of PI biosynthesis will also be identified. The Lopes lab has previously identified transcription factors and promoter elements that regulate PIS1 expression. These results suggest regulatory networks that will be tested for effects on PI biosynthesis. Collectively, this project will identify networks that regulate PI biosynthesis. Dr. Lopes has a strong record of mentoring undergraduate, graduate, and high school students in basic research. This commitment is based on the philosophy that advances in research must be integrated with the development of the next generation of scientists and educators. This project will provide students the opportunity to address an important biological question: how is phospholipid synthesis coordinated with other cellular processes?

洛佩斯实验室的长期目标是以酿酒酵母为模型系统，了解真核生物中磷脂生物合成的调节。本项目主要研究PIS1的表达调控。该基因是合成磷脂酰肌醇(PI)所必需的。PI及其代谢产物在许多过程中发挥着重要作用，包括：染色质重塑、核外输出mRNA、囊泡运输和信号转导。尽管PI对细胞很重要，但人们对其水平是如何调节的知之甚少。这个项目测试了多个细胞过程与PI的合成协调的假设。为了解决这一假设，我们将对PI的生物合成进行基因组分析。通过筛选酵母基因缺失集，洛佩斯实验室之前确定了120个影响PIS1报告基因表达的基因。这些基因表明，过氧化体功能和DNA修复等过程与PI的合成是协调的。将确定一组精选的这些基因在PI生物合成中的作用，并确定它们作用所需的五个PIS1启动子元件中的哪些。还将确定PI生物合成的直接调节因子。洛佩斯实验室此前已经确定了调节PIS1表达的转录因子和启动子元件。这些结果表明，将测试调节网络对PI生物合成的影响。总而言之，这个项目将确定调节PI生物合成的网络。洛佩斯博士在指导本科生、研究生和高中生进行基础研究方面有着良好的记录。这一承诺是基于这样一种理念，即研究的进步必须与下一代科学家和教育工作者的发展相结合。这个项目将为学生提供解决一个重要的生物学问题的机会：磷脂合成是如何与其他细胞过程协调的？