Genomic analysis of phosphatidylinositol synthesis in yeast

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。 该项目的重点是PIS1表达的调控。 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重要作用，包括：染色质重塑、mRNA从细胞核的输出、囊泡运输和信号转导。 尽管PI对细胞的重要性，但对其水平如何调节知之甚少。 该项目测试了多个细胞过程与PI合成协调的假设。为了解决这一假设，将进行PI生物合成的基因组分析。 通过筛选酵母基因缺失集，Lopes实验室此前鉴定出了120个影响PIS 1报告基因表达的基因。 这些基因表明过氧化物酶体功能和DNA修复等过程与PI合成协调。 PI生物合成中的作用将被确定为一组选择这些基因，其中五个PIS1启动子元件所需的行动将被确定。 还将鉴定PI生物合成的直接调节剂。 Lopes实验室先前已经鉴定了调节PIS1表达的转录因子和启动子元件。 这些结果表明，监管网络将被测试PI生物合成的影响。 总的来说，这个项目将确定网络调节PI生物合成。 Lopes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家的发展相结合。 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：磷脂合成如何与其他细胞过程协调？

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?